Review

pubs.acs.org/CR

Cooperativity in Noncovalent Interactions

A. Subha Mahadevi and G. Narahari Sastry*
Centre for Molecular Modelling, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, India 500607
11. 3. Catalysis 2802
11. 4. Material Science 2803
12. Prospects and Outlook 2805
Author Information 2806
Corresponding Author 2806
Notes 2806
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Biographies 2806
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Acknowledgments 2806
References 2806

CONTENTS
1. Introduction
2. Origin of Cooperativity
3. Hydrogen Bonding and Cooperativity
3. 1. Hydrogen-Bonded Clusters
3. 2. Hydrogen Bonding in Peptides and Carbo-
hydrates
3. 3. Hydrogen Bonding-Interplay with Other
Noncovalent Interactions
4. Quantitative Definitions for Cooperativity
4. 1. Many Body Analysis
4. 2. Double and Triple Mutant Analysis
4. 3. Measures for Estimation of Cooperativity in
Noncovalent Interactions
4. 3. 1. Interaction Energy and Energy Decom-
position Analysis
4. 3. 2. Spectoscopic Parameters
4. 3. 3. Structural Analysis
5. How Does a Pair of Noncovalent Interactions
Mutually Influence Each Other?
5.1. Cation-Induced Cooperativity
5.2. Anion-Induced Cooperativity
6. Strong Manifestation of Weak Interactions
7. Interplay of π−π Interactions
7.1. With Other Noncovalent Interactions
7.2. In Molecular Clusters
8. Modulation of Cooperativity Due to Solvation
9. Cooperativity in Biochemistry
9.1. Allostery and Binding Cooperativity
9.2. Multimeric Proteins, Ion Channels, and
Enzymes
9.3. Drug Receptor Interactions
9.4. Protein Folding
9.5. Transcription
9.6. DNA/RNA
10. Anticooperativity
11. Manifestation of Cooperativity
11. 1. Self-Assembly
11. 2. Chelate Cooperativity
1. INTRODUCTION
After conquering the atomic structure about a century ago,
2775 chemists have been largely interested in understanding the
2777 concept of chemical bond and the formation of a molecule from
2778 its constituent atoms.1 Electrons, nucleus, as well as the nuclear
2778 particles have their individual characteristics and give rise to
different types of elements, which make up our periodic table.
2782 Molecules, which are formed from these atoms, possess their
characteristically exquisite properties depending not only on the
2783 type of atoms but also on the way in which they are connected.
2784 These connections, known as chemical bonds, are at the heart of
2784 chemistry and provide the rational power to engage in a beautiful
2784 excursion toward the design of molecules through making and
breaking bonds. Therefore, in the contemporary age whenever a
2785 chemist, or for that matter any natural scientist, refers to a pure
compound, such as benzene, water, or even more complicated
2785 structures such as taxol, fullerenes, etc., they refer to their
2786 molecular structures.
2786 Clearly, molecules are individual building blocks, and the way
in which they organize themselves have a great bearing on their
2786 properties. We all know that the structure of most matter is
2786 determined by the way in which molecules associate with
2790 themselves, giving rise to different states of matter, and it is
2791 particularly interesting that in the condensed phases, the
2792 properties of molecules behave very differently depending on
2792 the temperature, pressure, volume, the presence of other
2793 molecules, interfaces with surfaces, environment, and under
2794 varying electric or magnetic fields. In all cases, while the molecule
2795 as an entity is intact, the way in which noncovalent forces operate
2795 with molecules of the same type or with other molecules or
surfaces is the key in determining these variations. Under-
2797 standing the nature of noncovalent interactions is thus extremely
2798 important to see what causes these variations in the proper-
2799 ties.2−9 The most dramatic changes in the properties of the
2800 molecules occur in condensed phases, in liquid and solid, as the
2800 way in which noncovalent interactions operate. Further, the way
2801 in which two molecules interact with each other are largely
2801 governed by a combination of dispersion2,8 and electrostatic
2801
2802 Received: June 30, 2014
Published: February 3, 2016

© 2016 American Chemical Society 2775 DOI: 10.1021/cr500344e

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Chemical Reviews
interactions. So much so that hydrogen bonding is one of the
most popular noncovalent interactions and in a colloquial sense
is almost synonymous with noncovalent interactions.10−13 On
the basis of the structure of interacting molecules, cation−π
interaction,14−17 π−π stacking,18 CH···π interaction,18 anion−π
interaction,19−23 halogen bond,24 lone pair interaction25 and so
on and so forth have emerged (Figure 1). Indeed, the origin of
Figure 1. Representation of the different kinds of noncovalent
interactions.
attraction in these interactions is electrostatic, induction, and
dispersion interactions. While most of these interactions are in
general weaker than covalent interactions, the strength of some
of the bonds such as hydrogen bond, cation−π, and anion−π can
have a varied range and in some particular instances might be
even slightly stronger than a weak covalent bond.
Figure 2. Manifestation of cooperativity in highly varied fields.
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Review
Noncovalent interactions were first recognized by J. D. van der
Waals in the later part of 19th century helping in reformulation of
the equation of state for real gases.2 Unlike covalent interaction
which leads to the formation of a classical molecule, noncovalent
interaction leads to the formation of molecular clusters. Some
noncovalent interactions are also known to act at long distances
of several angstroms unlike covalent bonds.3−7 For example, the
electrostatic, induction, and dispersion interactions are long-
range interactions, while the exchange-repulsion and charge-
transfer interactions are classified as short-range interactions.
The short-range interactions have their origin in the overlap of
molecular orbitals and do not act at long distances. Although
these interactions are traditionally considered to be weak, their
strength covers a substantial range, starting from a few kJ/mol to
several hundreds of kJ/mol depending on the type of interaction.
Earlier reports by Kollman have indicated how using the study of
noncovalent complexes indeed involves a fruitful interplay
between theory and experiment.3
Conventionally, from a chemical point of view, the nature of a
given chemical bond, for example a C−C bond, remains largely
unaffected by its surroundings.1 This is the basis for developing
molecular mechanics force fields, hybridization, and as such
giving an estimation of bond energies of a typical bond pair as
shown below.
ki ki
E (r N ) = ∑ (li − li ,0)2 + ∑ (θi − θi ,0)2
bonds 2 angles 2
Vn
+ ∑ [1 + cos(nω − γ )]
torsions 2 (1)
Signature of a typical covalent bond is that its bond length,
bond strength, as well as the spectroscopic signatures are usually
characteristic, and any modulations in their strength by
neighboring covalent bonds tend to be a small percentage of
its absolute value. Thus, in general, variations in the covalent
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bonds are not very dramatic. However, noncovalent interactions
can vary remarkably. Let us consider the C−C single bond in
ethane and propane which are comparable in their length and
strength which remains largely so in the congeneric series of
alkanes. However, let us take a dimer of water connected through
a hydrogen bond and compare it with a trimer, tetramer, and a
larger polymer. It has been unambiguously established that the
average hydrogen bond strength dramatically increases, with the
concomitant shortening of hydrogen bond length, becoming
almost double when it reaches a decamer.13 Thus, the way in
which the noncovalent interactions interact with themselves is
certainly not additive. Hydrogen bond strength ranges from a
very weak interaction to somewhat comparable with a weak
covalent bond. Similarly, the strengths of cation−π and π−π
interactions can be altered by two to three times, higher or lower
depending on the environment. One more important aspect in
any given process of aggregation is the large number of
noncovalent interactions that operate simultaneously. Thus,
noncovalent interactions are a topic of outstanding importance,
in all areas of chemistry, material science, biology, and medicine.
The additive scheme used in eq 1 for covalent bonds
encounters utter inadequacies when applied to systems governed
by noncovalent interactions. The underlying reason for this
failure is well-known nonadditivity. This nonadditivity arises due
to the cooperativity or anticooperativity of noncovalent
interactions. In the current review, we try to describe the
concept of cooperativity among noncovalent interactions.26−32
When a pair of noncovalent interactions strengthen each other, it
is called cooperative while when they weaken each other they are
defined as operating in an anticooperative manner. Cooperativity
implies that the sum of at least two interactions is larger than the
simple addition of the individual interactions. The terms
cooperative and anticooperative have different origins and
meanings in different fields28,33−36 and are extensively used in
biology (Figure 2). Although the qualitative concept of
cooperativity is quite clear, quantitative experimental measures
barring some spectroscopic approaches are rather scarce.
Computational quantum chemical methods provide the most
relevant means of probing and quantifying cooperativity. It is
interesting to examine the strength and limitations of quantum
chemical methods and the dependence of the cooperativity
measure on method, basis set employed, basis set superposition
error, etc. Knowledge of how noncovalent interactions manifest
themselves in small molecular clusters and the quantification of
their cooperativity and anticooperativity thus appears to be
essential for comprehension of supramolecular assembly.37,38
In the current review, we start with a discussion on the origin of
cooperativity. Historically, cooperativity has been studied
extensively in hydrogen-bonded systems and is thus discussed
as a prelude to the section on its quantification and measurement.
From a fundamental point of view, it is interesting to examine
how a pair of noncovalent interactions mutually influences each
other. In addition to hydrogen bonding, noncovalent inter-
actions such as cation−π, anion−π, and other weak interactions
have a strong manifestation in controlling supramolecular
structure and function. Among the noncovalent interactions,
cation−π may be argued to be stronger, while π−π and CH−π
interactions are weaker compared to hydrogen bonding. We
divide the review into sections on cooperativity in hydrogen-
bonded clusters, cation−π induced cooperativity, anion−π
induced cooperativity, and cooperativity among weak inter-
actions. Finally, the impact of cooperativity in understanding
various phenomena such as formation of supramolecular
2777
Review
assemblies, catalysis, and biological function is taken up. An
extensive review of the available literature on cooperativity also
reveals how cooperative behavior has aided substantially toward
understanding the conformational transitions and allosteric
interactions in proteins. Cooperativity is thus a concept of vital
importance in chemistry, biology, material science, and allied
areas.26−36 The synergistic interplay between different kinds of
noncovalent interactions is crucial to maintain the structure of
important biomacromolecules like DNA and proteins and in
retaining the fidelity of information processing needed for
normal life. In the field of chemistry too, cooperativity of
noncovalent interactions has an essential role in template-
directed synthesis, the transmission of stereochemical informa-
tion, and in determining the structure and properties of
materials.39−43
2. ORIGIN OF COOPERATIVITY
An explanation of the origin of cooperativity is helpful for
understanding various cooperative effects. The cooperativity
reported in this review can be classified into the following types
based on origin: (a) many body interaction, (b) secondary
interaction, (c) chelate effects, and (d) cooperativity and
anticooperativity induced by conformation change.
The many body interaction is a major source of the
cooperativity in the clusters of small molecules and is the origin
of hydrogen bond cooperativity. It not only considers the sum of
pairwise interactions but also includes three-body terms, four-
body terms, and so on. The contribution of different
intermolecular forces to many body interaction is very well
summarized in the book, The Theory of Intermolecular Forces by A.
J. Stone.44 The main contributions to forces between molecules
may be classified into long-range and short-range. Three kinds of
long-range effects are mentioned below. The electrostatic effect
arises from the classical interaction between the static charge
distributions of the two molecules. They are strictly pairwise
additive and may be either attractive or repulsive in nature.
Dispersion refers to the attractive term of the vdW equation. This
attractive part of vdW interactions is an electron correlation
(quantum mechanical many-body) effect known as London
dispersion.9 The contribution of dispersion to the many body
interaction is small. Induction effects arise from the distortion of
a particular molecule in the electric field of all its neighbors and
are always attractive. As the fields of several neighboring
molecules may reinforce each other or cancel out, induction is
strongly nonadditive.44 Because the origin of the induction
interaction is the induced polarization by electric field, the many
body interaction is particularly significant in cases where the
interacting molecule or ion has a strong electric field such as the
Mg2+ ion. Another vital aspect of the many body effects is the
modification of intermolecular forces between molecules in the
presence of a solvent.
The secondary interaction is another important source of
cooperativity.45−51 The secondary electrostatic interactions
rationalize the relative stabilities of multiple hydrogen-bonded
complexes. In multiple hydrogen-bonded complexes, the
arrangement of the hydrogen bond donor (D) and acceptor
(A) decides the total stability of the complex. Using molecular
mechanics calculations on nucleic acid base pairs, Jorgensen et al.
elucidated that secondary interactions between neighboring
heteroatoms can contribute additional stabilization, provided
that hydrogen bond donors with their positive partial charges are
present in one molecule and acceptors in the other molecule
(DD, AA).45−47 Repulsion between diagonally placed acceptor
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and donor functions will destabilize the primary hydrogen bond
when both molecules contain alternating sequences (e.g., AD,
DA, etc.). Jorgensen et al. also reported the importance of
secondary electrostatic interactions due to polar functional
groups located closely to hydrogen bonding sites.46 Studies by
Uchimaru et al. revealed that although the main source of the
stabilization for hydrogen-bonding association was the electro-
static contribution, the secondary electrostatic and polarization
interactions due to polar functional groups located closely to the
hydrogen bonding sites also significantly alter the magnitude of
hydrogen-bonding stabilization.48 Uchimaru and co-workers also
reported that the hydrogen bond donor−acceptor orientation
had an important role in cooperativity.49 Their case study in
three iso-complexes of C8H9N5O2 showed that when a hydrogen
bond is formed at the neighboring hydrogen bond site, the
intrinsic hydrogen bond forming abilities of hydrogen bonding
sites in the DA type molecules are increased, while those in the
AA and DD type molecules are decreased.
Another important source of cooperativity is the chelate
effect.28,52−54 The loss of the entropy of translation which is
associated with the cluster formation increases Gibbs free energy.
If molecules can bind by two interactions, the formation of the
second binding does not accompany the loss of the entropy of
translation. This is the origin of chelate effect. Williams and co-
workers52,53 have extensively discussed the general relevance of
enthalpy/entropy compensations to binding interactions of
biological importance in particular with respect to the binding of
agonists versus antagonists to a common receptor site. The
chelate effect is one of the important sources of the stability of β-
sheet structure, in which many hydrogen bonds exist.
The major source of cooperativity in biological systems is one
which is induced by conformational change. Typical examples of
cooperativity in biology are the binding of oxygen to hemoglobin,
wherein binding at each of its four binding sites increases the
oxygen affinity of the other sites, and in the folding of proteins
and nucleic acids that are characterized by sharp melting
transitions.26 Indeed the origin of this kind of allosteric
cooperativity is quite different from the origin of cooperativity
found in clusters of small molecules bound by intermolecular
forces.
The hydrophobic interaction55 has its origin in the change of
the structure of liquid water associated with the hydrophobic
molecules. A study by Chandler56 suggests that water molecules
can still form a hydrogen bond network around a small solute
molecule, although it is constrained by the presence of the solute.
The solvent entropy is reduced while the enthalpy remains
unaffected. The hydrophobic force has long been considered as
the major driving force of protein folding.57 When a protein
folds, the hydrophobic side chains are embedded within the
protein, leaving the hydrophilic side chains at the surface.
3. HYDROGEN BONDING AND COOPERATIVITY
Hydrogen bonding has been a subject of extensive study, and
several key reviews are available in literature revealing its wide-
ranging importance.58−64 In most cases, hydrogen-bonded
clusters have been employed to model cooperativity. Historically,
the first mention (to our knowledge) of cooperativity can be seen
in the paper of H. S. Frank and W. Wen in Discussions of Faraday
Society.10 The authors made a dramatic observation that “the
formation of hydrogen bonds in water is predominantly a
cooperative phenomenon, so that, in most cases, when one bond
forms, several (perhaps “many”) will form, and when one bond
breaks, then, typically, a whole cluster will “dissolve” ”. This is
2778
Review
quite a remarkable statement, and spectroscopic advances and
computational methods have enabled one to quantitatively
estimate the extent of cooperativity after almost 3−4 decades
after the observation. Dannenberg and co-workers have
undertaken a series of studies on amide clusters and ascertained
the cooperativity in these hydrogen-bonded clusters.65−67
Besides, a plethora of experimental and computational studies
which evaluate cooperativity in hydrogen-bonded clusters have
also been reported over the last two decades.68−151 The areas
which have witnessed the liberal use of the word cooperativity in
the context of hydrogen bonding include delineation of peptide
and carbohydrate structure152−176 and also the concept of
resonance-assisted hydrogen bonding.177−179
3. 1. Hydrogen-Bonded Clusters
Water clusters have remained as the most favored model systems
while investigating the intermolecular forces that act among
them, especially with regard to nonadditive interaction
energies.11,68−95 Beginning in the late 1960s Morokuma and
Pedersen68 and Kollman and Allen69 were among the first to
carry out ab initio Hartree−Fock calculations for a pair of
interacting water molecules. In 1970, Moskowitz and co-workers
employed SCF calculations to investigate the potential of
interaction for dimers and trimers of water molecules.70 The
study clearly revealed how three-molecule nonadditivities are
large in magnitude and vary in sign depending on the hydrogen
bond pattern involved. Huyskens reported a study on factors
governing the influence of a first hydrogen bond on the
formation of a second one by the same molecule or ion.11
Several experimental studies have addressed the structure and
spectra of small water clusters, ice, as well as larger three-
dimensional water clusters.43,71−74,93 A few experimental studies
which were employed to study hydrogen bond cooperativity are
mentioned below. A study of self-association and hydrogen
bonding of 3,4,5-trichlorophenol with water using matrix-
isolation FT-IR spectroscopy provided experimental proof for
the dominating role of the induction energy term in the three
body effect.77 Saykally and co-workers reported the quantifica-
tion of hydrogen bond cooperativity in the water by measuring
the far-infrared vibration−rotation tunnelling spectrum of the
perdeuterated water tetramer.43 Pate and co-workers have
employed broadband rotational spectroscopy on water clusters
produced in a pulsed molecular jet expansion to determine the
oxygen atom geometry in three isomers of the nonamer and two
isomers of the decamer.75 The cooperativity effects revealed by
the hydrogen bond O−O distance variations in this study were
shown to be consistent with a simple model for hydrogen
bonding in water that takes into account the cooperative and
anticooperative bonding effects of nearby water molecules.
Schmidt and co-workers reported an alternative interpretation of
the structure of the IR vibrational mode [υ(OH) band] of pure
water.76 The reinterpretation was based on the influence of the
cooperative hydrogen bonding arising from a network of
hydrogen bonds in the liquid. The insights obtained by foregoing
experimental studies have generated a lot of interest among
theoretical and computational chemists.
Ab initio studies for the ground states of the linear water dimer
with Cs symmetry and cyclic water tetramer with S4 symmetry
were undertaken by Lesyng and co-workers.79 Employing a
cooperativity parameter based on the two-body, non-neighbor
interaction energy, plus three- and four-body contributions,
including one-body deformation terms in relation to the total
interaction energy of the water tetramer, they demonstrated an
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Figure 3. Pictorial representation of four different kinds of arrangements of water clusters (W1D, W2D, W2DH, and W3D clusters) employed to
evaluate cooperativity as a function of arrangement of individual molecules in a cluster of particular size. Edited and reprinted from ref 84. Copyright
2010 American Chemical Society.
energy gain of 29% based on cooperativity in the S4 water
tetramer with the MP3/6-31G** approximation. Suhai convinc-
ingly elucidated that hydrogen bonding in ice is a highly
cooperative phenomenon where the optimization of the
structure of the infinite water polymer at the MP2 level yielded
a relative enhancement of 47% over the corresponding dimer
value.80 Further, the study revealed that the cohesive energy of
ice results from a delicate balance between different repulsive and
attractive terms in third and fourth order, which exhibit different
long-range behaviors. Xantheas studied the significance of all
higher-order components for interaction energy, in particular,
the three-body term among the nonadditive terms for water
clusters ranging in size from clusters trimer through pentamer.81
Hydrogen-bonding networks wherein donor−acceptor arrange-
ments existed between all water molecules were associated with
the largest nonadditivities among other networks present in low-
lying minima of small water clusters. Yáñez and co-workers
performed an ab initio study on water trimers and identified a
global minimum which corresponded to an asymmetric cyclic
structure.82 This structure presented significant cooperative
effects compared to a Cs dimer as reflected in several parameters
such as a stiffer intermolecular potential, shorter O−O distances,
longer donor O−H bond lengths, larger energies per hydrogen
bond, and greater shifts of the donor O−H bond stretching
frequencies than the Cs dimer. Studies on hydrogen bonding in
phenol, water, and phenol-water clusters by Subramanian and co-
workers have demonstrated the enhanced stability on account of
hydrogen bonding, although for clusters with a similar hydrogen-
bonding pattern, intermolecular interaction in phenol clusters
was slightly stronger than in water clusters.83
The impact of varying arrangements of water molecules in
different kinds of clusters as a function both of size of cluster (n =
2−20) and method of computation used have been studied by
our group using extensive density functional theory (DFT) and
ab initio calculations (Figure 3).84 These model systems served
to explain associated cooperativity in hydrogen bonding. The
ratio of complexation energy per hydrogen bond from decamer
to dimer [H2O10:2] and eicosamer to decamer [H2O20:10] was
calculated to quantify the strength of hydrogen bond with
increase in cluster size and was used as an indicator of
cooperativity that is seen in the water clusters. The complexation
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energy ratios ([H2O10:2], [H2O20:10]) revealed that the strength
of complexation energy increases by 33, 38, 35, and 91%,
respectively, as cluster size increases from 2−10 in four different
kinds of arrangements analyzed. As the cluster size increases from
10−20; however, the increase in strength of hydrogen bonding is
in the range of 4−6% only. Hence the nonadditivity of hydrogen
bond strength or the associated cooperativity was much more
evident as cluster size increased from 3−10 rather than from 10−
20, where the augmentation of hydrogen bond strength is only
marginal for all the four arrangements. Thus, the presence of a
definite amount of cooperativity in hydrogen-bonded water
clusters where the addition of a subsequent monomer to a
hydrogen-bonded cluster augments the strength of existing
interactions was inferred. The mode of arrangement, in
particular, how these interactions were arranged was shown to
play a crucial role on the strength of interaction.
Application of combined infrared spectroscopy and DFT
approaches by Ohno et al. demonstrated how the formation of
one hydrogen bond in a hydrogen-bonded water chain
cooperatively enhances or diminishes the strength of another
hydrogen bond.85 An observation of how cooperativity of the
hydrogen bonding of water molecules affects the corresponding
OH stretching bands was made. Quantum calculations
performed on a series of water clusters in order to mimic water
molecules found in restricted environment unlike bulk water
show that cooperative effects must be taken into account in the
treatment of hydrogen bonds and water clusters in such bounded
systems.86 Ruckenstein and co-workers focused on the role of
many-body interactions on the structure of ordinary ice and
liquid water revealing that 62−63% of hydrogen bonds must be
broken to disintegrate a large hexagonal ice piece used to
simulate water molecules in the form of a cube into small
clusters.87 Stokely et al. performed a study on the low-
temperature phase behavior of liquid water by combining
mean field calculations and Monte Carlo simulations.88 While
emphasizing key physical quantities that determine scenarios
which describe water, they report that it is the amount of
cooperativity in relation to the strength of the directional
component of the hydrogen bond that establishes which scenario
prevails. A recent study explores the impact of hydrogen bond
cooperativity in eight low lying water hexamers.89 Stabilizing
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cooperativity observed in linear hydrogen-bonded water systems
diminished as clusters move from nearly planar to three-
dimensional structures. Water molecules which donated both
hydrogens to form double-donating interactions had increased
stabilization, whereas waters which accepted two hydrogen
bonds experienced a decrease in stabilization due to cooperative
and anticooperative effects.
Studies on hydrogen-bonded clusters are not limited to water
clusters alone. 116−148 Dannenberg and co-workers have
contributed substantially to quantifying hydrogen bond
cooperativity by performing quantum chemical calculations on
several molecular clusters.65−67,101−107 Starting with ab initio and
semiempirical studies on 1,3 diones,65 dimers, and trimers of
acetic acid66 and acetylacetone67 to evaluate the strength of
hydrogen bonding, they further investigated how cooperative
interactions dictate the hydrogen-bonding structure. Employing
DFT calculations on chain and ribbonlike arrangement of
molecules, they demonstrated a high degree of cooperativity in
hydrogen-bonded chains of urea and formamide mole-
cules.101−103 Linear chains of hydrogen-bonded formamide
molecules containing from 3 to 15 monomeric units revealed a
cooperative effect, wherein the strongest hydrogen bonds,
typically those nearest the center of the formamide chain, have
a bond strength which approaches 200% that of the dimer.104
Further, vibrational frequencies of the coupled N−H, CO
stretches, and C−N stretch/CNH bend revealed clear shifts that
reflect the cooperative stabilization of the hydrogen bonds.105
We have performed a structural and energetic comparison of
linear, circular and standard arrangements of (acetamide)n
clusters (n = 1−15) at the B3LYP/D95** level of theory to
reveal significant cooperativity of hydrogen-bonding and size-
dependent structural preferences (Figure 4).108 The standard
arrangement in this study is defined as one where the maximum
number of hydrogen-bonding interactions are found while being
Figure 4. Two factors considered while studying cooperativity in
acetamide clusters (ref 108), size of clusters and difference in types of
arrangements for clusters of the same size. BSSE corrected interaction
energy per hydrogen bond (in kcal/mol) calculated employing the
B3LYP/D95** level of theory with dispersion correction is indicated in
the figure for selected clusters.
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subjected to free optimization without any emphasis on the kind
of order in the structure that is attained on optimization. The
interaction energy per monomer increased from dimer to 15mer
by 90% in the case of circular arrangement, by 76% in the case of
linear arrangement, and by 34% in the case of a third standard
arrangement, respectively. The cooperativity in hydrogen
bonding for acetamide clusters was evaluated by considering
the variation in geometrical parameters including bond distances
and electron density values at the bond critical point in the
different model systems. Similarly, DFT calculations were
performed on four arrangements of formamide clusters
[HCONH2]n, (n = 1−10) linear, circular, helical, and stacked
forms.109 These studies reveal maximum cooperativity, based on
interaction energy per monomer, in the stacked arrangement
followed by the circular, helical, and linear arrangements,
respectively. In all arrangements, an increasing trend in
cooperativity of hydrogen bonding was observed as a function
of increasing cluster size. Parra and co-workers reported DFT
studies on intermolecular bifurcated hydrogen-bonding inter-
actions in diformamide chains110 and carbonic acid clusters,111
showing the existence of significant cooperative effects in a linear
network of three-center bifurcated hydrogen bonds as well as
two-dimensional ringlike networks. There are two types of
bifurcated three-center hydrogen bond interactions they have
explored: (a) one that involves a hydrogen atom and two
acceptor atoms denoted as A1HA2 and (b) one that involves one
acceptor atom and two hydrogen atoms denoted as H1AH2.
Positive cooperativity observed in these studies helps to
rationalize the common occurrence of three-center H bonds in
the crystals structures of many molecular systems. Cooperativity
in intramolecular bifurcated hydrogen-bonding interactions has
also been reported by them.112 Ludwig et al. analyzed the
temperature dependence of NMR chemical shifts and quadru-
pole coupling constants in neat N-methylacetamide using
experimental and ab initio quantum cluster equilibrium (QCE)
theory.113 Strong cooperative effects were found in the linear N-
methylacetamide molecular clusters (n = 3−5) as reflected in the
chemical shifts and quadrupole coupling values for each species.
Theoretical calculations on smaller (HCN)n clusters where n =
1−4 at the RHF and MP2 level and for larger clusters where n =
5−7 at the RHF level of theory have shown that large cooperative
effects of hydrogen bonding are reflected in increasing hydrogen
bond energies, decreasing intermolecular separations, increasing
average dipole moments and in C−H stretching frequencies
shifts and the corresponding intensities as a consequence of
increasing cluster size.114 Theoretical computations on systems
consisting of up to four hydrazine molecules illustrate a
significant contribution of cooperative phenomena to the
interaction energy, amounting to as much as 12% of the overall
interaction energy.115 DFT calculations to examine the effect of
hydrogen bond cooperativity on the magnitude of the NMR
chemical shifts and spin−spin coupling constants in a C4h-
symmetric guanine-quartet and in structures consisting of six
cyanamide monomers have been reported.116 The study showed
that the magnitude of the NMR properties along the hydrogen
bond network, for example the |1JNH| coupling and 1H and 15N
chemical shifts of the hydrogen-bonding amino N−H group and
the |h2JNN| trans-hydrogen bond coupling, increased for
structures containing a larger number of monomers. Wang and
co-workers have proposed a rapid method to predict the
hydrogen bond cooperativity in long N-methylacetamide chains
containing up to 200 monomers.117,118 It is based on parameters
obtained from fittings to the hydrogen-bonding energies in N-
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Figure 5. Representation of (a) different water, formamide, and acetamide clusters employed to understand modulation of hydrogen bond cooperativity
in the presence of H+, Na+, Mg2+, OH−, and Cl− ions using DFT calculations (ref 131). (b) Plot showing BSSE uncorrected sequential binding energy
values obtained for one particular arrangement of water molecules named as W1D with five different ions and increasing cluster size.
methylacetamide chains containing 2 to 7 monomeric units
generated using ab initio calculations. A DFT study has revealed
significant contribution of cooperativity in the interactions of
hydrazoic acid clusters consisting of up to four monomers.119
Scheiner’s group probed into the underlying nature of the
CH···O interaction using the ab initio methods.120−124 They
thoroughly explored the cooperativity aspect of hydrogen bonds,
wherein a chain of n hydrogen-bonded molecules is held together
more strongly than would be expected based on the energetics of
the single hydrogen bond within a dimer.122 As mentioned earlier
in the section on origin of cooperativity, hydrogen bond
cooperativity is typically attributed in large measure to the
polarization induced in each subunit by the presence of its
hydrogen-bonding partner. Scheiner and co-workers focused on
evaluating the ability of one hydrogen bond in a chain to affect
others by comparing the CH···O bonds in (H2CO)n and
(HFCO)n to the OH···O bonds in (H2O)n.120,121 Although the
degree of cooperativity is generally proportional to the strength
of the hydrogen bond, the CH···O bonds in (HFCO)n were
shown to display a disproportionately high degree of
cooperativity. It was estimated that the mean hydrogen bond
energy in an infinite chain of H2CO molecules was 25% greater
than the same quantity in a dimer, while the long water chain
exhibits a 66% enhancement over (H2O)2. Inspite of containing
substantially weaker individual hydrogen bonds than those in
water chains, the study revealed that (HFCO)n manifests an
energetic cooperativity that is nearly as large as that of the OH···
O congeners. Cooperativity between the O−H···O and C−H···
O hydrogen bonds have been investigated by quantum chemical
calculations.125 The interaction energies of the O−H···O and C−
H···O hydrogen bonds were increased by 53% and 58%
respectively, demonstrating the presence of large cooperativity.
Grabowski and co-workers reported a study on H2CO···(HF)n
(n = 1, ..., 9) complexes using the MP2 method and showed how
cooperativity effect significantly enhances F−H···O hydrogen
bond.126 Chen and co-workers employed energy decomposition
approaches to quadruple and double hydrogen-bonded model
systems to emphasize how cooperativity is the most important
factor determining stability of the complex particularly in
quadruple hydrogen bond dimers.127 The cooperativity between
three types of hydrogen bonds (O−H···O, C−H···O, and O−
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H···π) in a cyclic complex involving one acetylene and two water
molecules has been studied.128 The total interaction energy of
the three hydrogen bonds was shown to increase as the number
of methyl group substitutions in the complex increases. MP2 and
DFT studies on linear (urea)n=3−10 clusters revealed how
cooperativity effects significantly enhance the N−H···O hydro-
gen bond from its strength of −7.90 kcal/mol in a dimer to
−11.39 kcal/mol in a decamer.129 Gadre and co-workers recently
reported the cooperative contribution toward hydrogen bonding
in para-substituted calix[n]arenes (CX[n]) (n = 4, 5) and their
thio analogues.130 Cooperativity was found to be nearly 5 times
larger in the parent structure than that to its thio analogue.
More recently, work done in our group evaluated the impact
that the presence of ions, such as Mg2+, Na+, H+, Cl−, and OH−,
has on hydrogen-bonded clusters of increasing size (water,
formamide, and acetamide [n = 1−10]) in the context of their
associated cooperativity using DFT calculations (Figure 5).131
The presence of an ion provides contrasting insight into the
evaluated sequential binding energies of hydrogen-bonded
clusters of different sizes. Dramatically higher sequential binding
energies were seen in the presence of ions initially for smaller-
sized molecular clusters compared to parent clusters. With
increasing cluster size, the difference in the sequential binding
energies between ionic clusters and parent clusters becomes
reduced. However, Mg2+-bearing clusters continued to exhibit
substantially higher sequential binding energies and coopera-
tivity, even with increasing cluster size. Monovalent ions had a
reduced impact on hydrogen bond cooperativity from hexamer
onward, and this may be indicative of the short-range over which
their influence prevails. The study helped reinforce the extent of
impact that divalent cations have on hydrogen-bonded chains as
against monovalent ions.
Zabardasti et al. reported presence of anticooperativity in
hydrogen-bonded clusters in two separate studies.132,133 Ab
initio calculations on dihydrogen-bonded clusters of BeH42− with
1−4 molecules of NH3 revealed how cooperative effect
decreased with the increasing size of the clusters.132 In another
study employing ab initio and DFT calculations on hydrogen-
bonded clusters of water cyanuric acid, the presence of both
cooperative and anticooperative effects were seen depending on
the geometry of the structures.133 Albrecht et al. considered the
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Figure 6. Selected crystal structures showing coexistence of different noncovalent interactions along with corresponding references where these
structures are reported. (a) Hydrogen bonding, π−π, and halogen interactions as seen in ref 182, (b) hydrogen bonding and π−π interactions noted in
refs 375, 372, and 373, (c) anion−π and π−π interactions seen in ref 302, (d) cation−π and anion−π interactions from ref 19, and (e) π−π interactions
and halogen bonds observed in refs 381 and 382.

changes in atomic energy in the clusters versus the isolated
monomer for small clusters of methanol, water, and form-
aldehyde. A variety of stabilities were observed within these
hydrogen-bonded clusters, including indications of cooperative
and anticooperative interactions.134
3. 2. Hydrogen Bonding in Peptides and Carbohydrates
Hydrogen bonds are the most important interactions between
amino acid residues in peptides and proteins as they provide the
stability for secondary structures like helices or sheets. Several
theoretical studies using α helix and β sheet model systems have
been performed to understand their inherent cooperativ-
ity.153−173 Kemp et al. used the experimental demonstration of
an enthalpic component to the cooperativity of α-helical peptides
as evidence for hydrogen bond cooperation in these
structures.162 This was done considering the helicity measured
at different temperatures in water for a solubilized polyalanine
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series. Using theoretical studies, Wu et al. clearly established the
existence of significant cooperativity in the formation of 310 and
α-helices, whereas no cooperativity was found in the formation of
β-strands and 27-ribbons for a series of polyglycine models
containing up to 14 amino acid residues.163 The absence of
significant cooperativity in terms of enthalpy contribution in β-
sheets was further shown by employing a model system
consisting of a dimer of a tripeptide to obtain repeating units
for the parallel and antiparallel β-sheets.164 Baker and co-workers
dwelt on the origin and relative importance of the contributions
to helical cooperativity.165 They also reported the role of
cooperative hydrogen bonding in amyloid formation.166
Dannenberg and co-workers performed ONIOM (DFT/
AM1) calculations on capped parallel-β-sheets of acetyl-
VQIVYK-NHCH 3 , acetyl-Q-NHCH 3, and acetyl-alanine-
NHCH3 as model systems to study the importance of hydrogen
bonding between glutamine side chains to the formation of
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amyloid VQIVYK parallel β-sheets.167,168 The Q sheets in these
studies exhibit cooperativity that is reminiscent of chains of
formamides104,105 and 4-pyridones,107 where the interactions
become stronger as the chain or sheet grows. Using both classical
electrostatic methods and DFT methods, the energetics of fibril
formation for the first three layers was shown to be cooperative.
Ireta et al. emphasized the importance of cooperativity in the
stability of α-helices.169 Two limiting cases were considered, one
of an isolated hydrogen bond and the other of an infinite α helical
chain for DFT studies. Cooperativity within an infinite network
of hydrogen bonds was clearly shown to strengthen each
individual bond by more than a factor of 2.
Jensen and co-workers reported a computational methodology
for backbone amide proton chemical shift (δH).170 Interestingly,
cooperative hydrogen-bonding effects were found to have a
significant impact on δH values by affecting the primary hydrogen
bond geometry and polarizing the electron density around the
amide proton. Magistrato and co-workers employed DFT and
hybrid DFT/MM simulations both in vacuum and in aqueous
solution on model polyglutamine β-sheet structures character-
istically observed in Huntington’s disease.153 Cooperativity of
glutamine side chains was shown to affect both directions,
perpendicular and parallel to the backbone. The unusual
behavior observed in these β-sheets provided significant extra-
stabilization of polyglutamine aggregation. Schreiber and co-
workers evaluated direct and cooperative contributions while
studying the strength of buried hydrogen bonds and salt
bridges.171 Employing a modifed multiple mutant cycle protocol
to selected interactions between TEM-1-β-lactamase and its
protein inhibitor BLIP, they demonstrated how formation of
network of interactions helps establish cooperative effects which
can convert even unfavorable interactions to favorable ones,
more so for salt bridges and to a lesser extent for hydrogen bonds.
Dashnau and co-workers used molecular dynamics (MD)
simulations combined with water−water hydrogen bond angle
analysis, calculation of solvent accessible surface area, and
approximate free energy of solvation to show how intramolecular
hydrogen bond cooperativity was closely associated with changes
in water structure surrounding the aldohexopyranose stereo-
isomers.174 Gadre and co-workers report a direct estimation of
individual intramolecular O−H···O interaction energies in sugar
molecules using the molecular tailoring approach (MTA).175
These studies reveal a contribution to the hydrogen bond energy
from the cooperativity to be typically between 0.1 and 0.6 kcal/
mol when hydrogen bonds were a part of a relatively weak
equatorial−equatorial hydrogen bond network and higher
between 0.5 and 1.1 kcal/mol when hydrogen bonds participated
in an axial−axial hydrogen bond network.
3. 3. Hydrogen Bonding-Interplay with Other Noncovalent
Interactions
Hydrogen bond operates in combination with numerous other
noncovalent interactions (Figure 6). A brief discussion on some
of the studies exploring their coexistence and their mutual impact
is given in the following section.180−214 In this context, Geerlings
and co-workers have investigated the interplay between aromatic
stacking and hydrogen bonding in nucleobases by employing
high-level quantum chemical calculations.180 Hydrogen-bonding
capacity of the N3 and O2 atoms of cytosine was shown to
increase linearly with the electrostatic repulsion between the
stacked rings. Superstructures of diketopyrrolopyrrole donors
and perylenediimide acceptors formed by a combination of
hydrogen bonding and π···π stacking have also been recently
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Review
reported.183 On the basis of a reductionist approach for the
construction of a micelle, Fernández and co-workers have shown
how highly directional hydrogen bonds build a frame on top of
which the dispersive forces give the aggregate its final shape.184
Lesarri and co-workers have determined the structures for
phenol dimer and trimer through the use of chirped pulse Fourier
transform microwave spectroscopy in the 2−8 GHz band.185 The
dimeric structure was found to represent a case, where an
interplay between dispersion and hydrogen bonding played an
essential role in fixing the complexation geometry.
A few studies also explore cooperativity of the dihydrogen
bond with other noncovalent interactions.150,151,186,187 Ren and
co-workers describe a cooperativity effect between the
dihydrogen bonding and H−M···π interactions (M = Li, Na,
and K) in ternary complexes of FH···HM···C2H2/C2H4/C6H6
using the DFT and MP2 level calculations.186 Analyses of the
charge of the hydrogen atoms in H···H moiety, atoms in
molecule (AIM) analysis, and electron density shifts methods
were adopted, and the cooperativity effect of the dihydrogen
bond on the H−M···π interaction was shown to be more
pronounced than that of the M···π bond on the H···H
interaction. The coexistence of both dihydrogen bonding and
metal−σ interaction was explored by Grabowski and co-workers
in the case of three aggregates H2···LiH···H2, H2···NaH···H2, and
H2···HBeH···H2 from among a series of complexes formed by
hydrogen with metal hydrides.187 They however report that the
modulus of the cooperativity energy is not greater than 0.05 kcal/
mol, suggesting that no significant cooperative effect is observed
in these instances.
In recent years, several studies on the interplay between
hydrogen bonding and the halogen bond have been
reported.188−195 Li and co-workers have performed ab initio
calculations on H3N···XY···HF triads (X, Y = F, Cl, and Br), each
having a halogen bond and a hydrogen bond.191 An analysis of
molecular geometries, binding energies, and infrared spectra of
monomers, dyads, and triads to examine cooperative effects
indicate significant cooperativity between the halogen and
hydrogen bonds in these complexes. Further effect of a halogen
bond on a hydrogen bond was more pronounced than that of a
hydrogen bond on a halogen bond. In another study, by means of
cooperativity of halogen bond with hydrogen bond and
substitution effect, the change of halogen bond from the
chlorine-shared one to an ion-pair one was successfully
realized.192 The substitution of alkali metal greatly strengthened
the halogen bond, while the cooperativity not only made the
halogen bond have a large change but also led to a large change in
the strength of the hydrogen bond. Meng and co-workers noted
the positive cooperativity between the HOX···OH/SH halogen
bond and the Y−H···(H)OX hydrogen bond in OH/SH···
HOX···HY (X = Cl and Br; Y = F, Cl, and Br) complexes by
means of MP2 level calculations.193 Further, the interplay
between hydrogen bonding and lithium bonding in the HLi-
NCH-NCH complex was studied with ab initio calculations. An
increase in binding energies by about 19% and 61% for the
lithium and hydrogen bonds, respectively, in the trimer were
noted.196
Yáñ ez and co-workers recently addressed cooperativity
between hydrogen bonds and beryllium bonds in (H2O)n BeX2
(n = 1−3, X = H, F) complexes.197 The changes in the atomic
energy components were correlated with the changes in the
strength of the interactions, thereby accounting for cooperative
or anticooperative effects. Russo and co-workers studied the
interplay between hydrogen bonding and both anion−π and
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lone-pair−π interactions for the global stability of halide-
dichlorotetraoxacalix[2]-arene[2]triazine using first principle
computations, highlighting that their combination leads to a
cooperativity effect.198 Emphasizing how hydrogen bonds have
indeed become a crucial functional and structural element in
modern inorganic chemistry, a combination of transition metal
ions and hydrogen-bonding interactions have been studied.199
Cooperativity between weak hydrogen bonds was revealed in
molecular clusters by examination of the structure, internal
dynamics, and origin of the weak intermolecular forces between
sevoflurane (1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane)
and a benzene molecule, using multi-isotopic broadband
rotational spectra.200 Thus, a large number of systematic
investigations mentioned in the section above have established
the modulation of hydrogen bond strength through coopera-
tivity.
4. QUANTITATIVE DEFINITIONS FOR COOPERATIVITY
The quantification of cooperativity differs based on the approach
and the nature of the system employed.215−253
4. 1. Many Body Analysis
Several studies attempt to get a quantitative account of the
cooperative effects by decomposing the interaction energy of a
system of n bodies and by inclusion of the many body terms in
the analysis.145,215−227 Axilrod and Teller215 and Muto216 were
apparently the first to provide an explicit treatment of the
nonadditive interaction energies in 1943. Hankins et al.
investigated the potential of interaction for pairs and triplets of
water molecules and made a representation for the individual
terms in the many body expansion for these small water
clusters.70 A quantitative measure of the cooperative effect is
made by decomposing the interaction energy of a system of n
bodies. Typically, the energy of the cluster in consideration can
be broken down into 1, 2,..., n body contributions via the many
body decomposition, where the 1-body term provides the
monomer distortion or relaxation energy. The many body
expansion of interaction energy for a system with N monomers in
it is given below
N N
E(1, .., N ) = ∑V 1B
(i ) + ∑ V 2B(i , j)
i i<j
N complexes.231 Any difference between the functional group
+ ∑ V 3B(i , j , k) + ... + V nB(1, ..., N )
i<j<k
where
2 workers have performed extensive studies using double and triple
V 2B = E(1, 2) − ∑ E (i )
i=1
3 3
V 3B = E(1, 2, 3) −
∑ E ( i , j) + ∑ E ( i )
i<j i=1
1B
V (i) is the one-body (1B) potential, which gives the energy
that is required to deform an individual molecule from its
equilibrium geometry. V2B and V3B are the two-body interaction
and three-body interaction terms where E(1, 2) is the dimer
energy and E(1, 2, 3) represents the trimer energy. The three-
body and higher interaction terms reflect the nonadditive or
cooperative effects typically seen in hydrogen-bonded clusters.
The many-body expansion indeed represents a powerful
Review
approach to study condensed phases as it offers a method to
arrive at the energy of an N-molecule system that can be
expressed as a sum of lower-order interactions which may be
obtained with reasonably high accuracy. Xantheas reported the
importance of the nonadditive terms in particular the three-body
terms as being responsible for determining the relative stabilities
of various trimer through pentamer isomers of water clusters.81
Almeida and co-workers demonstrate through many body
decomposition analysis, the importance of a proper representa-
tion of the cooperative effects in hydrogen fluoride by way of
inclusion of at least the three-body terms.145 Recent advances in
this context include the development of a 3-body:many-body
integrated fragmentation method for weakly bound clusters,
specifically finding application in the case of water clusters
(H2O)n, n = 3−10, 16, and 17.217 This technique captures all 1, 2,
and 3-body interactions with a high-level electronic structure
method, whereas a less demanding method is used to obtain 4-
body and higher-order interactions. Another variant in this
approach particularly with respect to evaluation of the interaction
energies of large clusters (H2O)n=6,16,24 from many-body
expansion involves reconstruction of the cluster from small
subclusters with a much lower computational cost.218 This is
done by applying progressively lower-level methods for
subsequent terms in the many-body expansion. Rapid con-
vergence of the many-body expansion is the key to such a
stratified approximation many-body approach. While studying
complex microscopic nonadditivity effects in hydrophobic
interactions and their impact on protein folding, Chan and co-
workers evaluated potentials of mean force of three-body
hydrophobic association of three methanes in water.219 Recently,
Matsumoto has reported a study on the four-body cooperativity
observed while surveying the effective attraction force between
hydrated methane molecules.220
4. 2. Double and Triple Mutant Analysis
Thermodynamic double mutant cycles and triple mutant boxes
are widely employed for the experimental quantification of
noncovalent interactions and cooperative effects in pro-
teins.26,228−234 Double mutant cycles were originally devised to
investigate the interactions in proteins.228,229 Chemical double
mutant cycles help to measure the magnitude of a particular
functional group interaction in both weakly and strongly bound
interaction energies in two systems was shown to provide a
measure of the magnitude of the enthalpic chelate effect in the
(2) complexes.233 Two double mutant cycles can be formally
combined to produce a triple mutant box, providing a general
method for quantification of cooperative effects. Hunter and co-
mutant cycle experiments to evaluate cooperativity in non-
(3) covalent interactions.26,231−233 Quantification of intermolecular
functional group interactions in hydrogen-bonded zipper
complexes in chloroform231 and in two different doubly
hydrogen-bonded motifs in carbon tetrachloride, chloroform,
(4)
1,1,2,2-tetrachloroethane, and cyclohexane form part of their
studies.233
Schreiber and co-workers have provided an experimental
approach to evaluate the net binding free energy of buried
hydrogen bonds and salt bridges in selected interactions between
TEM-1-β-lactamase and its protein inhibitor, BLIP.171 Results
from this study demonstrate the importance of forming networks
of buried salt bridges and suggest that the cooperative
networking effect results from the favorable contribution of the
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protein to the interaction. Ullmann et al. have recently reported
free-energy calculations within a continuum electrostatics model
to analyze the coupling of protonation, reduction, and
conformational change in azurin from Pseudomonas aerugino-
sa.230 Free energy measures of cooperativity are used for a
detailed analysis of the above-mentioned changes revealing how
cooperative free energies are useful in detecting and quantifying
thermodynamic coupling between events in biomolecular
systems.
Measures of cooperativity based on a combination of
mathematical modeling and experimental data are available in
few studies.55,29,137,235−245 Mariuzza and co-workers used surface
plasmon resonance techniques along with modeling on a
trimolecular protein complex as a model system for quantifying
cooperativity.237 The complex considered in this instance was
obtained by the simultaneous interaction of a superantigen with
major histocompatibility complex and T cell receptor. This study
reports both cooperativity and anticooperativity, besides
revealing an augmentation of the temperature dependence of
binding kinetics upon the cooperative interaction of different
protein components in the complex. Jauch and co-workers have
developed a method to measure heterodimer cooperativity
through a factor which reveals the mode of Sox-Oct transcription
factor heterodimerization on composite DNA elements.238
Roubeau and co-workers have reported a direct, experimental,
quantitative measure of the cooperative character of the spin-
crossover phenomenon in triazole-bridged Fe(II) spin-crossover
one-dimensional materials.240 The cooperative character of the
spin-crossover in these materials was quantified using the so-
called Slichter and Drickamer and domain models based on data
obtained from differential scanning calorimetry. Mas and co-
workers have emphasized the hierarchical approach to
cooperativity in macromolecular and self-assembling binding
systems.241 A global association quotient which was defined as Kc
= [occupied sites]/([free sites] L), with L being the free ligand
concentration was employed. This coefficient Kc easily relates to
other measures of cooperativity such as the Hill number or the
Scatchard plot and also to the free energies involved in the
binding processes at each ligand concentration. Douglas and co-
workers investigated specific models of self-assembly where the
self-assembly arises through the presence of nonlocal constraints
such as thermal activation, chemical initiation, and formally
constrained reaction order on the self-assembly process.242 A
comparison of basic thermodynamic characteristics of these
models to those obtained for a cooperative model and an
idealized noncooperative reference model were reported. Piguet
and co-workers suggest a combination of two simple indexes
measuring intermetallic (IcMM) and interligand (IcLL) interactions
as part of a thermodynamic model developed for quantitatively
estimating cooperativity in supramolecular polymetallic [MmLn]
self-assemblies.243
4. 3. Measures for Estimation of Cooperativity in
Noncovalent Interactions
4. 3. 1. Interaction Energy and Energy Decomposition
Analysis. We have defined the cooperative energy Ecoop in a
ternary complex of phenol, metal cation, and hydrogen bond
acceptors in our group.181 The extent to which the hydrogen
bonding and cation−π interaction act in concert in these ternary
systems can be deduced quantitatively by comparing the overall
reaction energy ΔE123 with the three individual interaction
energy terms i.e., ΔE12, ΔE32, and ΔE13. The direct assembly of
the ternary complex from its constituents hydrogen bond
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Review
acceptor (1), phenol (2), and metal cation (3) proceeds with
reaction energy ΔE123.
Ecoop = ΔE123 − ΔE12 − ΔE32 − ΔE13 (5)
ΔE123 = E123 − E1 − E2 − E3 (6)
Two different routes adopted for the stepwise formation of the
ternary complex were explored. The first one involved initial
formation of the hydrogen-bonded complex followed by
subsequent addition of the metal cation to form the ternary
complex. A second stepwise pathway was constructed in a
completely analogous mode by initial addition of the metal cation
to the phenol π-system and subsequent formation of the
hydrogen bond. The computed positive cooperativity between
cation−π and hydrogen-bonding interactions was rationalized
through RVS (reduced variational space) analysis. A repulsive
contribution of electrostatic interaction working in an anti-
cooperative fashion during the formation of the ternary complex
was noted. This anticooperativity however was smaller in
magnitude compared to the polarization component of phenol
which was essentially responsible for the net positive
cooperativity.
In another study, we gauged cooperativity in ternary
complexes formed by two aromatic benzene rings (BB) and a
benzene ring with a cation (viz. Li+, Na+, K+, NH4+, PH4+, OH3+,
and SH3+) (IB) in representative complexes.248 Similar to the
study mentioned earlier, the magnitude of cooperativity in a
ternary complex was calculated by deducting all pairwise
interactions from the total complexation energy of the trimer.
The complexation energy of the trimer corresponded to the
energy involved in the direct assembly of the ternary complex
from its constituent monomers which were two benzene units
and a cation. While two of the three two-body terms represent
the cation−π and π−π interaction energies, the third term
represents the through space cation−π interaction energy
between the cation and the second benzene ring with which it
does not have any contact. Besides several other studies have also
employed energy decomposition schemes to evaluate contribu-
tion of various factors to cooperativities.129,189,246,247,249−251
Grimme and co-workers subjected the intermolecular interaction
energy of nucleic acid trimers from a benchmark data set to an
energy decomposition analysis (EDA) to reveal that nonadditive
effects are mainly due to induction, while exchange repulsion,
electrostatic, and dispersion contributions are essentially
additive.251 In a study employing quantum chemical calculations
to investigate N−H···O hydrogen-bonding properties in linear
(urea)n=1−10 clusters, Morokuma analysis for all the clusters and
DFT-SAPT analysis for the urea dimer were performed.129 The
DFT-SAPT analysis of the interaction energy components
indicates that the electrostatic and dispersive interactions are
indeed the most important attractive terms in the urea dimer.
The interaction energies of several structures of guanidinium−
benzene complexes and anion approaching in different directions
were further dissected into their electrostatic, exchange,
repulsion, polarization, and dispersion contributions by means
of local molecular orbital energy decomposition analysis.250
Besides the electrostatic cation−anion attraction, the effect of the
anion over the cation−π interaction was shown to be mainly due
to polarization and could be rationalized following the changes in
the anion−π and the nonadditive terms of the interaction. Datta
and co-workers have applied an energy decomposition analysis
scheme to mixed cation (Li+, Na+, and K+) and anion (F−, Cl−,
and Br−) complexes on π-surfaces.252 Electrostatic interactions
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were found to be repulsive between the π-surface of benzene and
the anion F−•. Dispersion interactions were also significant in
providing stability to these complexes. While studying the
cooperativity of hydrogen- and halogen-bonding interactions in
Cl−···HCCH···HF, Cl−···ClCCH···HF, and F−···ClCCH···HF
complexes, Grabowski showed that all hydrogen bonds and
halogen bonds which existed in the corresponding dyads were
enhanced in the triads.189 The polarization term of the energy of
interaction was found to be most important for the halogen-
bonded systems. Symmetry-adapted perturbation theory
(SAPT) was applied to systems where pnicogen bonds and
cation−π interactions coexist in the same complex, in order to
understand the nature of the interactions and the mechanisms of
cooperative and diminutive effects operating in such com-
plexes.249 Electrostatic interaction played a major role in the
change of cation−π interaction strength in the ternary systems
considered in this study, whereas the change of pnicogen
bonding strength was shown to be caused jointly by the
electrostatic, induction, and dispersion interactions.
4. 3. 2. Spectoscopic Parameters. Maes et al. have
employed matrix-isolation FT-IR spectroscopy as a suitable
experimental method for evaluating hydrogen bond coopera-
tivities in a case study for self-association and hydrogen bonding
of 3,4,5-trichlorophenol with water.77 Using two cooperativity
factors, one representing the fortification of a hydrogen bond A−
H···A−H by a further A−H···B interaction in a 1:2 complex A−
H···A−H···B and another representing the inverse fortification,
differentiation between open, linear structures, and closed, cyclic
trimers was shown to be possible. Ohno et al. have also employed
matrix-isolation infrared spectroscopy and DFT to understand
the effect of cooperative hydrogen bonding on the OH
stretching-band shift for water clusters.85 While establishing
cooperativity in amide hydrogen-bonding chains, Dannenberg
and co-workers have compared between vibrational coupling
through hydrogen bonds and covalent bonds for polyglycines in
β-strands and chains of hydrogen-bonding formamides.104,156,167
Through a study on G-quartet, cyanamide rings, and the linear
cyanamide chain with identical monomers, van Mourik et al.
showed that in the absence of geometric variations, the
magnitude of the NMR parameters changes when hydrogen-
bonding monomers are progressively added to extending ring or
chain structures.116 The influence of cooperativity on the
frequency shift of the Ar−H stretch vibration in HArF complexes
has also been studied.253 Varfolomeev et al. have used a
combination of FTIR spectroscopy and quantum chemical
calculations on complexes of catechol and phenol along with
different proton acceptors.239 A measure of cooperativity based
on stretching vibration frequency shifts was developed, and this
frequency shift in a complex with cooperative hydrogen bonds
was determined from the IR spectra of catechol with equimolar
quantity of bases in the gas phase. The cooperativity measure
(Ab) employed for the same is shown below.
O − H ···· O − H ··· B
ΔνHB
Ab = O − H ··· B
ΔνHB (7)
where ΔνO−H···O−H···B
HB represents X−H (X−O or N) stretching
vibration frequency shift in the complexes with the adjacent
hydrogen bonds and ΔνHB O−H···B
indicates X−H stretching
vibration frequency shift in a complex with a single hydrogen
bond.
In the case of clusters where hydrogen-bonding interaction is
manifested, N−H stretching frequency shifts to a lower value and
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its intensity increases. The extent of decrease in N−H stretching
frequency depends on the strength of hydrogen-bonding
interaction. With an intention of demonstrating variation in
cooperativity among different arrangements of acetamide and
formamide clusters of increasing size, we compared the
magnitude of shift in N−H stretching frequency in each
arrangement.108,109 This was done using two parameters, average
N−H stretching frequency value for each cluster, and deviation
of average N−H stretching value from that computed for a
monomer. The decrease in value of average N−H stretching
frequencies leading to a red shift in larger clusters correlates to
enhanced hydrogen bonding and was used to explain
cooperativity.
4. 3. 3. Structural Analysis. Analysis of variation of the
structural parameters of different groups involved in the
hydrogen bonding as a consequence of their cooperative nature
is performed in several studies.111,112,118,159,254 Studying
cooperativity in amide hydrogen bonding lead Kobko and co-
workers to examine the relationship between the CO and C−
N bond distances as a function of the hydrogen-bonding chain
length and the position of the formamide in linear chains clearly
reflecting a structural response by each formamide unit to the
hydrogen bonding within its chain.105 Futher as the chains
become longer and the formamide monomer becomes more
central, the CO distances were shown to increase, while the
C−N distance decreased. Dannenberg and co-workers also
compared the structures and energies of β-strands, α-helices, and
310-helices for capped polyalanines, acetyl(ala)nNH2, for values
of n from 2 to 18, using mixed DFT/AM1 calculations.158 Potent
cooperativity of α-helices were manifested structurally by
decreasing O···H distances as n increases, energetically by
increased stability per hydrogen bond, and from dipole
moments. The effect of the methyl group on the cooperativity
between three types of hydrogen bond (O−H···O, C−H···O,
and O−H···π) in a cyclic complex was explored in a study by Li et
al.128 Addition of methyl group lead to enhancement of O−H···π
and O−H···O hydrogen bonds, and weakening of C−H···O
hydrogen bond. Performing DFT and hybrid DFT/MM
simulations of polyglutamine β-sheet structures in vacuo and in
aqueous solution, it was observed that the cooperativity of
glutamine side chains affects both the directions perpendicular
and parallel to the backbone.153 Energetic as well as structural
aspects such as shortening of hydrogen bond lengths and
increasing the number of hydrogen bonds involved were
undertaken. The cooperativity of hydrogen bonding in different
arrangements of water, acetamide, and formamide clusters of
increasing size was also manifested by a regular decrease in
average O···H and C−N bond distances, while average CO
and N−H bond lengths increase with increasing cluster
size.84,108,109
5. HOW DOES A PAIR OF NONCOVALENT
INTERACTIONS MUTUALLY INFLUENCE EACH
OTHER?
5.1. Cation-Induced Cooperativity
Cation−π interactions are arguably the strongest among
noncovalent interactions and have been shown to be modulated
by several factors.14−17,41,64,248,255−278 A number of experimental
and theoretical studies which elucidate cation-induced cooper-
ativity have also emerged.249,279−299 Our group has investigated
the fundamental question of how a pair of noncovalent
interactions mutually impact each other, especially when one
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Figure 7. Schematic representation of approach taken to demonstrate how M−π and π−π interactions work in concert, and the subtle π−π interaction
becomes substantial in the presence of a metal ion. (a) Interaction energies (in kcal/mol) of the metal ion with the benzene monomer and dimers and
(b) π−π interaction energies (in kcal/mol) of the various benzene dimers in the presence of metal ions at the MP2/6-311++G**// MP2/6-31G* level
of theory are shown. Edited and reprinted from refs 270 and 271. Copyright 2006 American Chemical Society.

of them is a cation−π interaction. In this regard, two scenarios
were studied systematically. In the first case, cooperativity
between cation−π interaction and hydrogen bonding181 was
dealt with and in the second instance between cation−π and π−π
interactions.248 In an earlier effort, the common coexistence of
M−π and π−π interactions in biology and chemistry has been
explored to garner a better understanding of how one kind of
noncovalent interaction affects the strength of another (Figure
7).270,271 This mutual impact is typically described in terms of
cooperativity and anticooperativity in bonding. The occurrence
of M−π−π (M = Li+, K+, Na+, Mg2+, and Ca2+) interactions in the
CSD (Cambridge Structural Database) and PDB (Protein Data
Bank) databases have been investigated and compared with the
number of exclusive M−π motifs. Besides, different forms of
benzene dimers (PD-parallel displaced, S-stacked, and T-
shaped) were also subjected to ab initio calculations as part of
this study, to establish the relative preference of differently
oriented aromatic moieties to bind to each other. The PDB was
then searched for metal ion containing structures having less than
3 Å resolution and a R value < 0.3. A total of 1941 protein
structures containing the 5 metal ions were then subjected to
analysis following removal of redundancy. The database analysis
revealed several salient points: (i) there was a high occurrence of
M−π and M−π−π interactions in chemistry and biology. (ii)
The prevalence of M−π−π was observed to be higher in most
cases or comparable to that of exclusively M−π configurations.
(iii) The number of M−π−π motifs present was only marginally
lower than the number of metal ions available. (iv) In proteins,
the aromatic amino acid side chains seemed to prefer the PD−M
and TB−M (T-shaped alignment of the benzene rings with M
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beside the T) orientations. Besides the database analysis, a
computational study was also undertaken. Interestingly, the
enhancement of π−π interaction in the presence of metal ion was
found to be quite substantial, especially when the metal had a
higher charge. Mg2+ ion enhanced the strength of the π−π
interactions by almost more than 5-fold in the three
configurations of benzene, S−M, PD−M, and TB−M. There-
fore, the strength of subtle π−π interactions transformed to
substantial, in the presence of a metal ion. Significantly, the
interaction between the two benzene rings in most orientations is
enhanced to an almost comparable extent. The influence that the
metal ion has on the first ring could be the major source of the
enhanced interaction. Thus, metal ion-assisted π−π interaction
strengths may become comparable in magnitude to that of the
hydrogen-bonding interaction.
As mentioned earlier, we have performed quantum chemical
calculations to gauge the effect of cation−π and hydrogen-
bonding interactions on each other.181 A model ternary system,
M-phenol-acceptor (M = Li+ and Mg2+; acceptor = H2O,
HCOOH, HCN,CH3OH, HCONH2, and NH3) was taken as it
exhibits both cation−π and hydrogen-bonding interactions
(Figure 8). Cooperativity was clearly quantified and defined,
and the computed positive cooperativity between cation−π and
hydrogen-bonding interactions further rationalized through an
energy decomposition scheme, reduced variational space (RVS)
and charge analyses. Although the direct interaction between the
metal ion and acceptor contributed to the cooperative
interaction, the enhancement of both the cation-π and the
hydrogen bonding energy, even in the absence of such
stabilization, was shown to be significant.
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Figure 8. Cooperativity between cation−π and hydrogen-bonding
interactions. Edited and reprinted from ref 181. Copyright 2008
American Chemical Society.
Extensive DFT studies and conformational analysis of
tryptophan, phenyalanine, and tyrosine in their ionic and dimeric
Figure 9. Pictorial representation of various noncovalent interactions observed in dimers of tryptophan (ref 272), tyrosine (ref 273), and phenylalanine
(ref 274), characterized using AIM analysis.
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forms have been recently reported by our group (Figure
9).272−274 In all these studies, the conformational space of
aromatic amino acid dimers has been explored by considering the
relative orientation of two aromatic moieties such as parallel
displaced, T-shaped, and stacked orientations, and the possible
hydrogen-bonding interactions between COOH and NH2
groups and also other noncovalent interactions between
aromatic rings and COOH and NH2 groups such as OH-π,
NH−π, and π−π interactions. The comparison of stability of
different dimeric forms studied reveals that the most stable
dimers predominantly possess hydrogen-bonding interactions,
while the ones with aromatic side chain interactions are less
stable. Thus, a delicate balance of noncovalent interactions and
their interplay governed the stability of different forms of the
studied aromatic amino acids and their respective dimers.
Rooman and co-workers have focused on the relative
importance of simultaneous cation−π and hydrogen-bonding
interactions in DNA staircase motifs.279 Nonadditive effects
induced by the different energy and entropy contributions both
in vacuum and in different solvents were explored, revealing how
in the absence of an estimation of the dispersion nonadditivity,
the cooperativity for guanine-argnine-guanine, cation−π, and
hydrogen-bonded stair motifs arises from the environment. 1H
NMR experiments and quantum chemical calculations by
Dutasta and co-workers emphasize the competing cation−π
and anion−π interactions involved simultaneously in the
molecular recognition process of selected zwitterionic neuro-
transmitters and a particular hemicryptophane.280 Li and co-
workers showed the prominent enhancing effect of the cation−π
interaction on the halogen−hydridehalogen bond in the
model systems, M1···C6H5X···HM2 (M1 = Li+, Na+; X = Cl, Br;
M2 = Li, Na, BeH, and MgH).281 The study showed that
halogen−hydride halogen bonding is indeed strengthened
greatly by a cation−π interaction. The interaction energy in
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Figure 10. (a) Schematic representation of ternary model systems containing 4-amino-2-iodophenol, Li+, NH2CH3, C6H6, and NH3CH3+ exhibiting
different kinds of noncovalent interactions, including cation-π (CP), hydrogen bond (HB), halogen bond (XB), π−π (PP), metal ion-lone pair (ML)
and charge-assisted hydrogen bond (CHB). (b) Complexation energy of the ternary systems, sum of complexation energy of binary systems (in free
state) present in the ternary systems and cooperativity energy of the ternary systems as obtained at the M06-2X/6-31G(d) (I: DGDZVP) level of theory.
Edited and reprinted from ref 275. Copyright 2015 American Chemical Society.

the triads was two to six times as much as that in the dyads.
Moreover, the nature of the cation, halogen donor, and the metal
hydride were shown to influence the nature of the halogen bond.
In another study, the effect of the methyl group on the
cooperativity between cation−π interaction and NH---O hydro-
gen bonding using ternary systems constituted with Na+,
pyrrole/methylated pyrrole, and water/dimethyl ether and the
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corresponding binary systems were explored by them.282 A
methylated pyrrole was shown to be favorable for the cation−π
interaction, whereas it was unfavorable for the NH---O hydrogen
bond. Further, an ab initio study of synergetic effects of two
strong interactions namely cation−π interaction and lithium
bond in the M+···phenyl lithium···N model system where (M =
Li, Na, K; N = H2O and NH3) revealed that cation−π interaction
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and lithium bonding in the trimers become stronger relative to
the dimers.283 An increase in interaction energy by 4.4−6.3% was
reported for cation−π interaction, while that of lithium bonding
increased by 5.2−15.9%. Lu and co-workers have investigated the
mutual influence between halogen bonds and cation−π
interactions using MP2 level calculations.284
Song and co-workers studied cation−π or cation−π−π
interaction between one cation and one or two structures
bearing electron-rich π systems.285 A new type of interaction,
cation⊗3π, in which one cation simultaneously binds with three
separate π-electron-rich structures was explored. An anomalous
increase in the order of the one-benzene binding strength of the
cation⊗3π interaction, with K+ > Na+ > Li+ at odds with the
conventional ranking of the binding strength, was noted. This
unexpected observation was owing to the cooperative interaction
of the cation with the three benzenes and also between the three
benzenes, wherein steric-exclusion effect between the three
benzenes played an important role. Frontera and co-workers
have demonstrated how the cation−π and hydrogen-bonding
interactions influence each other in complexes where both
interactions are present and also if such an interplay monotoni-
cally increases by adding further hydrogen bonds to the aromatic
systems.286 Cooperativity effects were demonstrated in another
study, when cation−π and lone pair−π interactions coexist in the
same system.287 Employing a combination of DFT and MP2
calculations on a binary complex formed by an O-cresol moiety
and a Na+ cation or two O-cresol monomers, as well as the
ternary system that contains a Na+ cation and two O-cresol units,
Ren and co-workers investigated the cooperativity effects
between the cation−molecule and hydrogen bonding.288
Cooperativity effect was observed in the conformations formed
by the moderate Na+···π, H···π, and H···O interactions, while the
anticooperativity effect was present in the complex with the
strong Na+···O cation−molecule interaction. The cooperativity
effect between dihydrogen bonding and H−M···π interactions
was also investigated where H···H and H−M···π interactions
were shown to be strengthened in the ternary complexes in
comparison with the corresponding binary system.289 Studying
the influence of the Li···π interaction of C6H6···LiOH on the
H···π interaction of C6H6···HOX (X = F, Cl, Br, and I) and the
X···π interaction of C6H6···XOH (X = Cl, Br, and I), Meng and
co-workers revealed that the addition of the Li···π interaction to
benzene weakens the H···π and X···π interactions.290 Ebrahimi et
al. were able to reveal the influence of cation−π and anion−π
interactions on the strength and nature of the N···H hydrogen
bond based on MP2 calculations in model systems.291
Cooperative and diminutive effects were found when halogen
and lithium−π bonds coexisted in the same complex considering
the case of CF3X-NCLi-C2H4, CF3X-CNLi-C2H4, and CF3X-
C2H4−LiCN (X = Cl, Br, I) complexes.292 Cheng et al. also
reported interesting cooperative and diminutive effects when
pnicogen bonds and cation−π interactions coexist in the same
complex.249
In a recent study from our group, we examined the key factors
that control the structures and energetics of the coexistence of
multiple noncovalent interactions.275 4-Amino-2-iodophenol
was taken as a model system which exhibits nine different
kinds of noncovalent interactions, including cation−π, hydrogen
bond through oxygen and nitrogen, halogen bond, π−π
interaction, metal ion−lone pair interaction through oxygen
and nitrogen and charge-assisted hydrogen bond through oxygen
and nitrogen (Figure 10). Indeed, very few studies have been
reported on the cooperativity in quarternary structures.141,293,294
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By careful consideration of all possible combinations of these
noncovalent interactions, based on energy, geometry, charge,
and AIM analysis, we have systematically evaluated the
cooperativity among 40 ternary systems and 105 quaternary
systems. A study of the quaternary systems revealed how
hydrogen bond, halogen bond, and π−π interaction work
together by enhancing each other’s strength. The study
highlights that the positively charged species enhance hydrogen
bond−hydrogen bond and hydrogen bond−π−π interactions
forming cooperative systems. Surprisingly, some of the
quaternary systems were also found to be cooperative in nature
despite the electrostatic repulsion between two positive charge
species involved.
Through a study of substituted anilines and benzylamines,
cooperative cation−π, π−π, and van der Waals interactions were
shown to be responsible for an increase in aromatic cationic
amine sorption to Na/Ca-montmorillonite, well beyond the
extent expected by cation exchange alone.295 Besides compounds
with greater amine charge/area and electron-donating sub-
stituents that allowed for greater electron density at the center of
the aromatic ring showed a greater potential for cation−π
interactions on montmorillonite surfaces. Hence, numerous
studies of cation-induced cooperativity have been in evidence in
the past few years.
5.2. Anion-Induced Cooperativity
In this section, several studies which employ theoretical
calculations and experimental examples to illustrate how
interplay exists between anion−π interactions and other
noncovalent interactions have been dealt with. Quite in contrast
to cation−π interactions, the generality of anion−π interactions
has come to light only in recent years. A few recent reviews also
highlight the increasing understanding of the role played by
anion−π interactions in supramolecular assembly.21−23 Mount-
ing experimental evidence for the presence of anion−π
interactions through elucidation of crystal structure of inorganic
complexes and biological macromolecules along with establish-
ing their functional significance has been reported.19,20
The coexistence of anion−π interactions with other non-
covalent interactions has also been revealed.250,252,300−322
Atwood and co-workers provided preliminary studies on anion
binding within the cavity of π-metalated calixarenes.19 They
reported the synthesis of tetrametallic hosts as anion receptors by
X-ray crystal structure investigations, clearly demonstrating a
cooperative effect arising from the arrangement of four metal
centers about a common, rigid binding pocket, resulting in
anion−host contacts. Hay et al. have summarized evidence for
existence of four distinct binding modes for complexes of anions
with charge-neutral arenes, including C−H hydrogen bonding
and anion−π interaction.306 Manzano and co-workers studied
anion encapsulation in metallic grids showing the presence of
two counteranions (BF4− or PF6−) hosted in the cavities,
exhibiting C−H···F and anion···π interactions in the solid
state.307 In the case of complexes with a methylated ligand,
aromatic π−π stacking interactions were also noted. Using a
combined crystallographic and theoretical approach, Frontera
and co-workers studied anion−π interactions in a series of
bisadenine derivatives dwelling in particular on the existence of
synergistic effects between π−π and anion−π interactions.308
Berryman et al. developed the experimental evidence for
interactions between anions and electron-deficient aromatic
rings.309 They were able to demonstrate how tandem hydrogen
bonds and anion−arene interactions augment halide binding in
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solution.310 Jentzsch et al. have recently demonstrated the
general functional relevance of anion−π interactions elucidating
how anion transport is achieved with halogen bonds.311 Notash
et al. established how a coordinated anion could control the
structural motif of one-dimensional coordination polymers
through multiple cooperative weak noncovalent interactions
such as hydrogen bonds, halogen---π and π−π interactions.304
Giese et al. investigated an anion−π complex between bromide
and a neutral receptor both in solid state and solution.312 A
definite role of a cooperative effect of the N−H--anion and
anion−π interaction was reported therein. Zaccheddu et al.
employed a combination of dispersion-corrected DFT and
quantum Monte Carlo calculations to rationalize the unusual
structural features observed in a nitrate−triazine−triazine
complex.313 This study emphasized that π−π stacking was not
only enforced by the coordination of the triazines within the
particular crystal structure but was regulated by cooperative
anion−π and π−π interactions, wherein the cooperative effect
amounted to 6% of the total binding energy.
The specific aspect of anion-induced cooperativity has also
been addressed through numerous theoretical studies.315−322
Extensive theoretical studies on the role of anion-induced
cooperativity have come from the group of Frontera and co-
workers.315−319,321,322 Studying the interplay between cation−π,
anion−π, and π−π interactions in trifluorobenzene π systems
along with selected metal cations and anions by applying
resolution of the identity MP2 level calculations revealed that
both the cation−π and the anion−π interactions have a strong
influence upon the π−π interaction and vice versa.315 They also
reported cooperativity effects in complexes, wherein anion−π
and hydrogen-bonding interactions coexist even at very large
distances (as long as 11 Å).316 Cooperativity effects have also
been reported by them in complexes where interplay between
lone pair−π or anion−π interactions and halogen bonding exists.
Cooperativity was observed even when the distance between the
anion and halogen bond donor molecule was longer than 9 Å.317
Unexpected nonadditivity effects were also reported in the case
of complexes of fluorine-substituted ethyne, ethene, butadiene,
benzene, and [n] radialenes (n = 3−5) with two anions at the RI-
MP2/aug-cc-pVTZ level of theory.318
Ab initio MP2 level claculations on 1,4-diiodo-perfluoroben-
zene working both as electron-deficient π aromatic ring and as
halogen bond donor with anions were performed by Lu et al.25
Distinct additive and diminutive effects were observed when
halogen bonds and anion−π/lone pair−π interactions were
present in the same complex. Cabaleiro-Lago and co-workers
clearly showed how the interaction energy was decomposed into
different two- and three-body contributions in complexes
consisting of guanidinium, benzene, and one anion.250 The
three-body interaction was demonstrated to be anticooperative
in the case of the presence of the cation and the anion on the
same side of the π system, whereas when the anion and the cation
were on opposite sides of the π system, the three-body
interaction was cooperative. Datta and co-workers have
employed dispersion-corrected DFT on mixed cation anion π
systems to reveal cooperative stabilization of the otherwise
weakly stable anion···π complexes.252 Decomposition of the total
interaction energies in these systems has shown that the
cooperativity among the interactions is indeed substantial and
as large as 100 kcal/mol. Thus, the anion-induced cooperativity
has emerged as an important mode of tuning several noncovalent
interactions such as hydrogen bonding, halogen bonding, and
cation−π interactions.
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6. STRONG MANIFESTATION OF WEAK
INTERACTIONS
Interestingly, a large number of studies on cooperativity among
several other weaker noncovalent interactions have come to light
in the past few years.323−361 Atwood et al. have shown the impact
of extensive cooperativity in maintaining the structural integrity
of a nonporous organic solid operating as a host compound for
guest transport.8 The host molecules were shown to be mobilized
in response to relatively weak van der Waals interactions with
small guest species such as vinyl bromide or toluene. Li et al.
studied the interplay between halogen bond and lithium bond in
the complexes of the form MCN-LiCN-XCCH where (M = H,
Li, and Na and X = Cl, Br, and I).24 The study reports distinct
cooperativity between the lithium bond and halogen bond where
the lithium bond has a larger enhancing effect on the halogen
bond, in a range of 11.7−29.4%. Using ab initio calculations,
Meng and co-workers have demonstrated the presence of
cooperativity in binary and ternary complexes of OCS···C6H6,
C6H6···Rg and OCS···C6H6···Rg (Rg = He, Ne, Ar, and Kr)
governed by van der Waals forces.324 Li and co-workers have
emphasized the importance of both electrostatic and van der
Waals interactions as being essential for describing the
cooperative interaction in long helices.325 In a specific study on
long α- and 310-helical polyalanines, the greater cooperativity of
α-helices over 310-helices in long helices was shown to originate
mainly from the much stronger van der Waals interaction in α-
helices. Recently, Grimme and co-workers have calculated the
energy profiles of the activation reaction of small molecules (H2,
Br2, and CO2) with boron/phosphorus frustrated Lewis pairs.326
While investigating the cooperative nature of the reactions using
interaction energies in the ternary system and for reactant pairs,
they proposed an isosurface representation of the many-body
deformation density (Δρmb) to serve as a qualitative tool to
visualize cooperative, nonadditive effects in complex chemical
systems. Ren and co-workers have employed DFT and ab initio
calculations on ternary systems of FH···HM···C2H2/C2H4/
C6H6, where M = Li, Na, and K and C2H2/C2H4/C6H6 represent
the π electron donor.186 The study reveals the cooperative nature
of interaction between dihydrogen bonding and H−M···π
interaction. Esrafili and co-workers have revealed a size-
dependent variation in atomic multipole moments as a useful
signature of lithium-bonding cooperativity in case of linear
clusters of (LiCN)n and (LiNC)n (n = 3−7), which are
connected via lithium bonds.327 Cooperative effects in the
geometry, energy, and electron density in the linear and cyclic
arrangements of clusters of interhalogen derivatives have also
been reported.328 Cooperative interplay between covalent and
noncovalent interactions have been explored both from the
perspective of crystal structure analysis341 as well as employing
theoretical calculations.330
Another important class of noncovalent interactions are the
σ−σ interactions which are decisive for alkyl group inter-
actions.362−369 Indeed, in the absence of polar functional groups,
dispersion dominates intermolecular interactions between
hydrocarbon moieties and is characteristic for CH−σ and
CC−π as well as for various other σ−π-mixed clusters. Schreiner
et al. reported the preparation and characterization of alkanes
with the longest C−C bonds observed to date (up to 1.704 Å),
whose surprisingly high thermal stabilities are due to a favorable
balance of repulsive and attractive van der Waals interactions
between the CH surfaces.363 σ Stacking can reach the energy of
chemical bonds, and a study by Schreiner et al. illustrates the
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point that σ−σ and π−π interactions are equally important.362
With regard to the properties of single-sheet [n]graphanes, their
corresponding double-layered forms along with multilayered
[n]graphanes (n = 10−97) were studied employing the
dispersion-corrected DFT in the above-mentioned study.
Interestingly, there is currently no evidence for cooperativity
for these interactions, and the association energies of multi-
layered graphanes per carbon atom are rather similar to their
double-layered forms and independent of the number of
layers.362 A benchmark comparison of σ−σ and π−π dispersion
in dimers of naphthalene and decalin and coronene and
perhydrocoronene showed that strong dispersion interaction
requires rigid subsystems and good fits of their repulsive
potential walls.367
7. INTERPLAY OF π−π INTERACTIONS
7.1. With Other Noncovalent Interactions
Several examples of coexistence of π−π interactions along with
other noncovalent interactions abound in litera-
ture.251,294,308,370−387 The presence of halogen bonding and
π−π interactions in the solid state structure of a butadiynylene
linked bidentate halogen bond donor was recently shown by
Taylor and co-workers.378 A cocrystal with tetra-n-butylammo-
nium iodide was also studied. An interplay of coordination and
π−π stacking interactions has been studied in cadmium(II)
iodide and thiocyanate complexes adopted by polycyclic 1,4-
bis(pyridazin-4-yl)benzene.377 Mattay and co-workers have
reported the synthesis of arene-functionalized 2-aminopyrimi-
dines, where hydrogen bonding and π−π interaction have a
significant contribution in the process of self-assembly on
account of their coexistence.372 Fu et al. revealed the crystal
structure of methyl 4-hydroxy-3-nitrobenzoate where 12 hydro-
gen bonding and two π-stacking interactions are shown linking
the molecules into infinite stacked sheets.373 Shishkin et al. have
conducted an analysis of the crystal structure of a set of
substituted 1,3,5-trihalobenzenes from the viewpoint of their
energy of intermolecular interactions.379 The study showed that
all crystals studied possess a columnar structure where the
presence of shearing mechanical properties is not caused by the
layered structure of the crystal but the character of interactions
between neighboring columns, including stacking interactions
and halogen bonds which are located near planes of molecules
belonging to different columns.
Theoretical and experimental studies on model systems which
mimic π−π interactions along with other noncovalent
interactions have also been reported.388−396 Rooman and co-
workers focused on a stair motif involving a cation−π and
hydrogen bond occurring in the DNA-binding domain of Tc3
transposase from Caenorhabditis elegans (1TC3) between Arg
C236 and the two successive Gua A7 and A8.279 This complex
was considered as a model system for studying the relative
importance of the three simultaneous interactions that is,
cation−π, hydrogen bonding, and stacking, with the resulting
nonadditive effects induced by the different energy and entropy
contributions, both in a vacuum and in different solvents.
Geerlings and co-workers subjected pyridine-substituted ben-
zene model complexes to MP2 level calculations in order to
ascertain influence of stacking on hydrogen bonding.384 This
study showed that the hydrogen-bonding capacity of the
nitrogen atom was directly related to the electrostatic interaction
between the cycles, more so to the electron-donating/with-
drawing character of the substituents. Rotello and co-workers
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reported the synthesis of a flavoenzyme model bearing a
diamidopyridine recognition element and several aromatic
units to mimic π−π and donor atom−π interactions commonly
found in nature.385 The study demonstrated that a subtle
interplay occurs between the hydrogen-bonding network and the
aromatic units which allows for maximum stabilization of the
cofactor in the reduced state. In an attempt to put the discussion
of the interplay of the various interaction energy contributions on
quantitative grounds, Hesselmann et al. have employed DFT-
SAPT methodology (symmetry adapted perturbation theory
based on DFT) on the Watson−Crick and stacked structures of
the adenine-thymine and guanine-cytosine base pairs.386 A good
agreement of total interaction energies for the cbs-extrapolated
DFT-SAPT deviating by an upward shift of 1.2−1.6 kcal/mol
from estimated cbs CCSD(T) results for stacked and Watson−
Crick structures of AT and GC was reported.
The cooperativity of π−π and cation−π interactions has been
clearly demonstrated by our group taking benzene as the
aromatic model system and a series of monovalent cationic
species, such as Li+, Na+, K+, NH4+, PH4+, OH3+, and SH3+
(Figure 11).248 Systematic quantum chemical studies were
Figure 11. Model systems employed to understand cooperativity
between cation−π and π−π interactions of ref 248.
performed to estimate the effects of cation−π and π−π
interactions on each other in cation-π−π systems. This study
has provided a simple model for cooperativity. All possible
orientations of onium ions to form cation−π complexes were
explored, and the most stable conformation was used to further
evaluate its effect on π−π interaction. A notable increase of 2−5
kcal/mol in the π−π interaction energy in the presence of the
cations was seen. The cation−π interaction energy was also
enhanced in the presence of π−π interaction albeit to a smaller
extent. The wide varieties of cations including both metal and
inorganic ions, employed in the study underline the generality of
the results obtained.
Martiń and co-workers have shown cooperativity between
π−π and hydrogen-bonding interactions through the formation
of a highly stable supramolecular complex formed from C60 and
exTTF (2-[9-(1,3-dithiol-2-ylidene)anthracen-10(9H)-yli-
dene]-1,3-dithiole).387 Grimme et al. studied the three-body
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Figure 12. Pictorial representation of absence of significant cooperativity in benzene clusters (ref 406) employed as model systems to understand
behavior of multiple π−π and CH−π coexisting with each other. Uniformly similar values of complexation energy per interaction in the two varied
arrangements in spite of increasing cluster size suggest additive nature of stacking and CH−π interactions in benzene clusters.
contribution to the interaction energy for a benchmark MP2
database of nucleic acid base trimers.251 They employed an
energy decomposition analysis scheme having similar definition
of energy terms to the Morokuma decomposition scheme to
reveal how nonadditive effects were mainly attributed to the
induction term, while exchange repulsion, electrostatic, and
dispersion contributions were essentially additive. Frontera and
co-workers have reported the presence of strong synergistic
effects in systems, wherein π−π interactions modeled using
benzene and hexafluorobenzene, coexisted with cation−π and
anion−π interactions in the same complex.294 Very high
nonadditivity energies ranging up to −20.3 kcal/mol were
observed, indicating how cation−π and/or anion−π interactions
have a strong influence on the π−π interaction and vice versa.
Presence of synergistic effects in complexes wherein edge-to-face
aromatic interactions and hydrogen-bonding interactions coexist
have also been studied.388 Besides, a minor impact of X−H/π (X
= C, N, and O) interaction on the π−π interaction and vice versa
has also been reported.389 Ab initio calculations employing the
RI-MP2 method on a choice model of interacting molecules,
namely 1,4-diaminobenzene and terephthaldehyde demonstra-
ted that synergetic effects were present in complexes where
hydrogen-bonding interactions, cation−π, and π−π interactions
coexist.390 Ebrahimi et al. performed ab initio calculations on X-
ben∥pyr···H−F (X = NO2, CF3, CN, F, Cl, CH3, and OH)
complexes to gauge the effect of π-stacking and hydrogen-
bonding interactions on each other.391 Cooperativity of
interactions in these complexes was noted where face-to-face
aromatic interactions and hydrogen-bonding interactions
coexist. Balasubramanian and co-workers have used several
structural parameters such as hydrogen bond length to measure
cooperativity in oligomers of benzene-1,3,5-tricarboxamide and
to study stacking based on quantum chemical calculations.392
Zarić and co-workers have shown remarkably stronger stacking
interactions of pyridines with hydrogen bonds due to local
parallel alignment interactions of OH bonds with the aromatic
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ring by analyzing data in CSD.393 Zhu et al. have also undertaken
a survey of the CSD for structures in which halogen bonds and
aromatic stacking interactions are present.394 They reported
cooperative effects in complexes in which the aromatic rings
behave both as electron donors in halogen bonds and as electron
acceptors in π−π stacking interactions. Strong cooperativity was
also shown to occur in the complexes involving pyrazine rings as
Lewis bases in some of the complexes.
7.2. In Molecular Clusters
Besides the above-mentioned studies, investigations into
molecular clusters which emphasize interplay between stacking
and CH−π interactions are also discussed in order to evaluate the
presence of cooperativity and anticooperativity in these
interactions.397−414 The benzene dimer has served as a prototype
for π−π and CH−π interactions.397,398 Tsuzuki and co-workers
have reported the CCSD(T) interaction energy of the benzene
dimer at the basis set limit for parallel, T-shaped, and slipped-
parallel orientations revealing that dispersion interaction is
indeed the major source of attraction in the benzene dimer,
although electrostatic interactions appear to be very important
for determining the directionality of the constituent benzene
molecules in cluster formation.397 Computations have been
limited to dimers, trimers, and few tetramers of benzene
molecules due to the huge requirement of computational
resources for the higher clusters.399−404 Heuristic search
techniques employing genetic algorithm for benzene cluster
optimization have also been pursued.405
Through an exhaustive study on clusters of benzene (Bz)n, n =
2 to 8, at the MP2/6-31++G** level of theory, we demonstrated
how the cooperativity in benzene clusters is quite insignificant,
which is in sharp contrast to the way in which hydrogen bonding
and some other noncovalent interactions operate.406 In order to
quantify the extent of cooperativity in a set of benzene clusters
(Figure 12), the complexation energy (CE) per interaction
between a pair of benzene molecules (CE/(n − 1), n = number of
benzene monomers in the cluster) was compared from trimer to
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hexamer. A near uniform CE/(n − 1) value of ∼3.3 kcal/mol
from trimer to hexamer in the case of parallel displaced stacked
clusters at the MP2/6-31G* level of theory was observed. The
corresponding value of CE/(n − 1) is approximately −6.5 kcal/
mol at the MP2/6-31++G** level of theory for the same
structures. The addition of another benzene molecule did not
seem to enhance the strength of each individual interaction. This
observation was quite in contrast to earlier reported studies
dealing with noncovalent interactions such as cation−π, π−π,
and hydrogen-bonding interactions. In the case of clusters where
CH−π interactions were more prominent, a similar absence of
cooperativity was observed. The CE per interaction values there
were in the range from −2.7 to −4.6 kcal/mol at the MP2/6-
31G* level and consistently about a couple of kcal/mol higher at
the MP2/6-31++G** level. An inspection of all the clusters and
their CEs revealed that the interaction energies were additive
irrespective of the number or type (CH···π or π−π) of
interactions. Hence stacking interactions in benzene clusters
seem to be essentially additive in nature. The cooperativity
observed in clusters of polar molecules is due to induction
interactions which play an important role in determining their
structure. As electrostatic interactions contribute little in the case
of benzene clusters, the resultant small induction interactions
may be the cause for negligible cooperativity that is observed.
In order to investigate how large π-networks can enhance the
stability of a protein conformation and influence protein−ligand
interactions, our group developed an Aromatic−Aromatic
Interaction Database, A2ID (Figure 13).407 In continuation of
earlier efforts on understanding how cooperativity can
strengthen the multiple interactions considerably, a qualitative
and quantitative study estimate for the 2π, 3π, and higher
aromatic repeat units within a threshold distance cutoff in
Figure 13. Schematic representation of the selection of π−π motifs
using a virtual sphere in the Aromatic−Aromatic Interaction Database
(A2ID), ref 407. The coordinate system used to define the centroid
position of the observed molecule (CB) relative to the reference
molecule (CA). The interplanar angle ϕ and normals to the planes of π-
systems, Nref and Nn+1. RNM is the distance between the two π-systems,
and R is the cutoff distance.
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proteins was undertaken. The study was also directed to reveal
any specific network and connectivity of aromatic rings in the
proteins. Although the distribution of π−π networks was found
to be ubiquitous across all family of proteins, a higher propensity
to be perpendicular to each other (CH···π) rather than parallel
was observed, considering orientation of π−π networks.
Using R2PI (resonant two-photon ionization) spectroscopy in
concert with electronic structure calculations, Reid and co-
workers have recently shown studies on the homoclusters of
chlorobenzene and also on bromobenzene and mixed homo-
benzene clusters, as prototypical systems where π−π stacking,
CH/π interactions, and halogen-bonding interactions may all be
present.395,408 Sherrill and co-workers demonstrated that the
interaction energies in larger benzene clusters were obtained as
the sum of interaction energies for isolated benzene dimers, with
an error of less than 10% for the systems considered.398,399
Waller and co-workers revealed parallel π-stacking was not a
good structural motif for promoting cooperative bindings in gas-
phase homotrimers.409 Further, anthracene trimers which
adopted predominantly stacked geometries showed additive
three body interaction energy reflective of the absence of
cooperativity, similar to pyrazine oxide and uracil trimers.
Additivity of π−π or π+−π stacking and T-shaped interactions
between natural or damaged DNA nucleobases and histidine was
investigated by Wetmore and co-workers.410 Although both
stacked and T-shaped interactions, as well as both π−π and π+−π
interactions, were shown to exhibit geometric additivity, they
obtained a small magnitude of additivity energy < 0.48 kcal/mol,
suggesting that these interactions are additive. The interaction
energy analysis however does not reveal whether the
nucleobase−amino acid interactions are equivalent in dimers
and trimers, or whether they differ in different-sized complexes
but sum to yield an overall additive interaction. An analysis of
how the biological backbone affects the π−π stacking
interactions between conjugated nucleobases and amino acids
has also been reported.411
8. MODULATION OF COOPERATIVITY DUE TO
SOLVATION
The presence of solvent and its impact on cooperativity have
been considered using both experimental and theoretical
studies.415−434 By determination of dynamic vapor pressure
measurements, Wolfenden et al. explored cooperativity and
anticooperativity in solvation by water for imidazoles, quinones,
nitrophenols, nitrophenolate, and nitrothiophenolate ions.415
Collum and co-workers showed that mixtures of ether and amine
solvents offer relative dimer binding energies in some cases and
provided evidence of cooperative solvation due to an absence of
mixed solvates.416
Addressing the question on whether cooperativity in hydro-
phobic association could be reproduced correctly by implicit
solvation models, Scheraga and co-workers evaluated the
potential of mean force (PMF) of the hydrophobic association
of pairs and triplets of nonpolar solute molecules with various
sizes and strengths of van der Waals interactions.417 Umbrella
sampling MD simulations combined with the weighted histo-
gram analysis method were employed for this purpose. The study
revealed that distance dependence of the PMF, including the
cooperative contribution, was described qualitatively correctly by
the variation of either the molecular surface area or the excluded
solvation-shell molecular volume with the distance between the
solute molecules. Jordan and co-workers have studied the
infrared spectra of I−·(CH3OH)n·Arm, n = 1,2 clusters, obtained
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via argon and methanol predissociation, with the aid of ab initio
calculations of their OH stretching fundamentals.418 A dramatic
OH red-shift relative to both the symmetric isomer and the n = 1
complex was traced to a cooperative hydrogen bonding which is
only operative in the asymmetric form.
Using correlated ab initio calculations, Scheiner and co-
workers have shown that conventional and OH···ϕ hydrogen
bonds obey the normal principles of cooperativity, wherein these
bonds are strengthened when a central molecule serves
simultaneously as both proton donor and acceptor, whereas
CH···O bonds do not appear to be amenable to such positive
cooperativity.419 As such, when placed in a polarizable medium,
all hydrogen bonds weaken as the dielectric constant of the
solvent increases. Spectroscopic studies of solvated hydrogen
and hydroxide ions at aqueous surfaces have been reported.321
The role of hydrogen-bonding cooperativity is investigated in
these studies.420
Microsolvation of the cation−π interaction has been explored
in detail by our group.421,422 The sequential attachment of water
molecules to cation−π (Li+-benzene, K+-benzene, and Mg2+-
benzene) systems revealed how solvation of the metal ion
decreases its interaction energy with the π system, while the
solvation of the π system increased its interaction energy with the
metal ion. The cation binding to benzene enhanced the ability of
aromatic protons to participate in hydrogen bonding with water
molecules. An interesting modulation of the strength of the
cation−π interaction as a result of other noncovalent interactions
was observed through these studies. Subsequently, in separate
studies on metal ion solvation423 including one modeling Na+
solvation424 and a second on Mg2+ solvation425 with increasing
number of water molecules (n = 1−20) employing DFT and
MP2 level calculations, the variation in the stability of the
complexes with the same number of water molecules could be
attributed to the hydrogen-bonding patterns observed in them.
The strength of hydrogen bonding between the surrounding
water molecules in the different coordination shells along with
the metal−water interaction was shown to play a key role in
determining the stability of the complex.
Kuo and co-workers adopted a combined theoretical,
spectroscopic approach to study how when a solvent molecule
is replaced by another molecule with larger proton affinity, the
strength of all other hydrogen bonds decreases.426 The concept
of anticooperativity by successive substitution was considered in
a mixed solvation system. H+(CH3OH)m(H2O)n (m + n = 5 and
6) mixed clusters were employed to demonstrate hydrogen bond
weakening. Recently Bakker and co-workers have shown an
important study wherein a combined terahertz and femtosecond
infrared spectroscopic study of water dynamics around different
ions including magnesium, lithium, sodium, and cesium cations,
as well as sulfate, chloride, iodide, and perchlorate anions, reveals
that the effect of ions and counterions on water can be strongly
interdependent and nonadditive and in certain cases extends well
beyond the first solvation shell of water molecules directly
surrounding the ion.427 Peruchena and co-workers have
performed ab initio calculations to demonstrate that the
hydrogen bonds are stronger in the dihydrated complexes than
in the corresponding monohydrated complexes, wherein the σ-
and π-electron delocalization were found.428 The importance of
ion cooperativity in understanding the osmotic coefficients of
salts and their effects on water surface tension has been explored
by Gao through simple theoretical models.429 The cooperative
effect of halogen bonding was considered by Cheng and co-
workers in H2CS−XY (XY = FF, ClF, ClCl, BrF, BrCl, and BrBr)
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complexes.430 The solvent effect on the halogen bond in the
H2CS−BrCl complex was also studied, and it was found that the
solvent has a prominent enhancing effect on it. Evaluating
solvation effect, particularly in terms of its impact on
cooperativity, is vital as there are a number of different molecules
of real biological relevance which are capable of forming a
multiplicity of hydrogen bonds and other noncovalent
interactions all at the same time. Although the last few decades
have seen a remarkable development of methods, techniques,
and algorithms to study solvation problems computationally,
there is still a need to dwell further into understanding the role of
solvation on cooperativity.
9. COOPERATIVITY IN BIOCHEMISTRY
The term cooperativity in biochemistry is used in a range of
processes such as preorganization, avidity, allostery, and some
types of macro molecular assembly. The underlying phenomen-
on in cooperative processes as is typically encountered is one in
which the binding of a ligand to one site alters the affinity of a
separate ligand molecule for binding at another site. Such a
cooperativity requires allosteric communication between binding
sites. Whitty describes the role of configurational preorganization
to be a second important phenomena underlying different
cooperative processes, for example those involving polyvalent
ligands or even as observed in protein folding.435 Besides,
consideration of protein folding illustrates that cooperativity is
not solely an equilibrium phenomenon but also a strategy used
by nature to increase reaction rates.435 Cooperativity may also be
more broadly defined as a process for which intermediates are
disfavored (resulting, for example, in a two-state conformational
change).436 Indeed, Williamson suggests that understanding
cooperativity provides an insight into the mechanisms that
govern assembly and disassembly of multicomponent com-
plexes.437
9.1. Allostery and Binding Cooperativity
The concept of cooperativity in binding is typically introduced
through a discussion of oxygen binding to hemoglobin (Figure
14).438−447 Eaton and co-workers have provided an account of
Figure 14. Depiction of cooperative binding in hemoglobin.
the novel physical experiments and rigorous quantitative analysis
conducted by several scientists over the decades to elucidate two-
state allosteric mechanism of hemoglobin.438 Starting with the
original work of Hill in 1910 on the possible effects of the
aggregation of the molecules of hemoglobin on its dissociation
curves,439 a large number of studies have been evolved that
provide models to rationalize the O2 binding curve of
hemoglobin and its associated cooperativity.440−443 Important
among the models formulated to explain this cooperativity was
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Figure 15. Structures from PDB showing coexistence of different noncovalent interactions.
the two-state concerted MWC model put forth by Monod,
Wyman, and Changeux in which with only three parameters
allosteric cooperativity was adequately described.444 Employing a
comparison between X-ray structures of liganded hemoglobin
and its deoxy form, Perutz filled in the lack of a structural
mechanism in the MWC model.445 Karplus and co-workers
subsequently presented an allosteric model of the statistical
mechanics of cooperativity to account for the dependence on
proton concentration, as indicated by the pH-dependence of
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ligand binding along with consideration for the earlier mentioned
MWC model and structural data.446 Ackers et al. later reported
how the allosteric mechanism was controlled by quaternary
switching from form T to form R occurs whenever heme-site
binding creates a tetramer with at least one ligated subunit on
each dimeric half-molecule.447 Cooperativity was demonstrated
to arise from both concerted quaternary switching and sequential
modulation of binding within each quaternary form, T and R.
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Early discussions on cooperativity of biological membranes in
terms of their lattice structure448 and suggestions of cooperative
transitions triggered by either a change in electric field449
(membrane potential) or in a ligand concentration or both have
been reported. Rebek et al. have shown that processes involving
small molecules in solution can be subjected to control involving
conformational changes induced by binding, and they also
reported an example of a model system which shows binding
cooperativity between two remote sites.450 Studies exploring the
consequences of thermodynamic stability on generalized binding
phenomena in biopolymers have also been undertaken.451,452
Allosteric cooperativity continues to capture current inter-
est.453−473 Bashford and co-workers suggested a mechanism
which requires no conformational change to produce a
cooperative effect considering cooperative binding of charged
ligands to proteins.461 The ligand binding sites were electro-
statically coupled to protein side chains that can undergo
protonation and deprotonation. Laughton and co-workers also
provided an example of the concept of allostery without
conformational change. This was done through a series of MD
simulations on the free DNA, the 1:1 complex, and the 2:1
complex with ligand Hoechst 33258 designed to enable
calculation of thermodynamic parameters associated with the
molecular recognition events.462 Fully solvated MD simulations
and quasiharmonic normal-mode analysis were performed on
chloroeremomycin, vancomycin, and dechlorovancomy-
cin.463,464 The study revealed that biochemical cooperativity
could be mediated through changes in vibrational activity,
irrespective of the presence or absence of concomitant structural
change. An exoditopic artificial receptor based on a hydrindacene
platform provided evidence that cooperativity in amide hydrogen
bonding by polarization plays a part in the positive homotropic
allosteric binding property with benzenediols.465 Through a
study on a tris-cation receptor wherein a clustering of
electrostatic interactions allows the efficient complexation of
amino acid carboxylates in water, Schmuck et al. have
emphasized how cooperativity functions even in small and
flexible artificial receptors.466 Hilser and co-workers have
investigated whether, in addition to serving as structural scaffolds
for recognition and catalysis, active-site residues may also play a
role in modulating the cooperative network.467 They employed
an experimentally validated ensemble-based description of
proteins to elucidate the extent to which perturbations at
different sites can influence the cooperative network in the
protein. A study on a saccharide receptor achieving concen-
tration-dependent mannoside selectivity through two distinct
cooperative binding pathways has been reported.468
Goodey et al. have reviewed how conformational mobility
serves as the common route between allosteric regulation and
catalysis, more so in the context of the role played by allosteric
effects in drug design and protein engineering.469 Veglia and co-
workers mapped the allosteric network in the catalytic subunit of
protein kinase A using NMR spectroscopy.470,471 Positive
allosteric cooperativity was shown to be generated by nucleotide
and substrate binding during the transitions through the major
conformational states including apo, intermediate, and closed
conformers. Kremer et al. have recently emphasized the
implementation of allosteric control in artificial receptors with
different combinations of effectors.472
9.2. Multimeric Proteins, Ion Channels, and Enzymes
Cooperativity serves as an important factor in the functioning of
multimeric complexes.474−478 Williamson has recently addressed
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the importance of understanding how cooperativity provides
insight into the mechanisms that govern assembly and
disassembly of multicomponent complexes.437 The quantifica-
tion of cooperativity in various multicomponent assemblies
through the construction of thermodynamic cycles and under-
standing the underlying dynamic equilibrium of the various
binding components, their rates of the association and
disassociation and associated free energies were discussed.437
Mariuzza and co-workers237 used surface plasmon resonance
techniques and mathematical modeling to describe the
energetics of cooperativity in a trimolecular protein complex.
They studied the ternary complex formed by the simultaneous
interaction of a superantigen with major histocompatibility
complex and T cell receptor to show how the system exhibits
both positive and negative cooperativity. Sleat et al. provided
genetic evidence for nonredundant functional cooperativity
between two different proteins involved in lipid transport.479
Zandany and co-workers report a strategy for direct analysis of
cooperativity in multisubunit allosteric proteins.480 They
measured effects of all possible combinations of mutated
subunits on protein function, along with analysis of the hierarchy
of inter subunit interactions, assessed by using high-order double
mutant cycle coupling analysis. Blacklow and co-workers
reported the X-ray structure of a dimeric human Notch1
transcription complex loaded on the paired site from the human
HES1 promoter.481 Analysis of this structure helped reveal how
promoter organizational features control cooperativity and the
responsiveness of different promoters to Notch signaling.
Selected examples of crystal structures from PDB showing
coexistence of different noncovalent interactions are shown in
Figure 15.
A large number of studies have shown that the activation of ion
channels are mediated through cooperativity.482−487 The highly
cooperative opening of calcium channels by nanomolar
concentrations of inositol 1,4,5-trisphosphate (IP3) enables
cells to detect and amplify very small changes in the
concentration of IP3 in response to hormonal, sensory, and
growth control stimuli was shown by Holowka and co-
workers.488 They investigated the kinetics of IP3-induced Ca2+
release from intracellular storage pools in permeabilized rat
basophilic leukemia cells to gain insight into the molecular
mechanism of action of IP3. Qian and co-workers examined the
mechanism of cooperative activation of big potassium (BK)
channels by Ca2+.489 Smith-Maxwell et al. have studied the role of
the S4 transmembrane segment in channel gating by constructed
chimeras in which S4 segments from several divergent potassium
channels, Shab, Shal, Shaw, and Kv3.2, were inserted into a
Shaker potassium channel background.490 Tombola et al. have
clearly shown how the opening of the two pores of the Hv1
voltage-gated proton channel is tuned by cooperativity.491 Zhou
investigating cooperativity in twin gatings reported patch-clamp
fluorometry measurements of cAMP binding and channel
opening combined with global kinetic fitting to reveal that
ligand binding to the tetrameric hyperpolarization-activated
cyclic nucleotide-gated channel is favored at the second and
fourth binding events.492 Fujiwara et al. focused on the molecular
basis for dimer formation and intersubunit coupling in Hv1/VSO
P, a dimeric voltage-gated H+ channel in which the gating of one
subunit is coupled to that of the other subunit within the
dimer.493 A cytoplasmic coiled-coil mediates the cooperative
gating temperature sensitivity in this voltage-gated H+ channel
Hv1.
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The activity of many enzymes are regulated by allosteric
effectors.34,457,494−498 Salahub and co-workers reported a study
employing DFT calculations to reveal a large cooperative effect
induced by the interaction of an anion with a peptide hydrogen
bond network, directly or through an imidazole molecule.499 An
increase of the cooperative effect on going from a neutral to a
negatively charged ligand was shown to be sufficiently large that
it could make an important contribution to the catalysis by
stabilizing the charge formation along the reaction pathway in the
enzyme-catalyzed reactions. Wulff and co-workers have explored
cooperativity of an amidinium and a copper ion in a transition-
state imprinted cavity giving rise to high catalytic activity based
on a model of carboxypeptidase A.500 Single molecule
enzymology have demonstrated dynamic effects that were
concealed entirely by ensemble-averaging techniques.501 Studies
with mutant human Monoamine Oxidase B revealed an allosteric
mechanism where the increased binding affinity of ligand results
from a cooperative increase in hydrogen bond strength through
formation of a more hydrophobic milieu.502 Hammes-Schiffer
and co-workers have proposed a general mechanism for enzyme
catalysis that includes multiple intermediates and a complex,
multidimensional standard free energy surface.503 Flexibility,
diversity, and cooperativity have found emphasis as pillars of
enzyme catalysis.
Positive cooperativity in some reactions involving cytochrome
P450 3A4 which oxidizes a diversity of substrates, including
various drugs, steroids, carcinide natural products, have been
reported.504 Guengerich and co-workers observed the presence
of positive cooperativity in oxidations of several substrates,
including testosterone, 17β-estradiol, amitriptyline, and aflatoxin
(AF) B1 in systems containing purified recombinant bacterial
P450 3A4.505 Studies on construction and characterization of a
site-directed mutant that displays hyperbolic steroid hydrox-
ylation kinetics to analyze human cytochrome P450 3A4
cooperativity were also reported.506 Oostenbrink and co-workers
adopted a combination of MD simulations and free-energy
calculations to elucidate the physicochemical origin of the
observed positive homotropic cooperativity in ketoconazole
binding to cytochrome P450 3A4.507 The binding of the first
ketoconazole molecule was established to increase the affinity for
the binding of the second ketoconazole molecule by 1.2 kcal/
mol, thereby explaining the experimentally observed cooperative
behavior of cytochrome P450 3A4. Shape complementarity
through van der Waals interactions was identified as the main
driving force of such a binding. Qian and co-workers have
suggested a cooperativity in the phosphorylation-dephosphor-
ylation cyclic reactions which is temporal, with energy “stored” in
time rather than in space as seen in allosteric cooperativity.508,509
This was done through stochastic models for different molecular
interactions involving signal transduction modules.
Phenolic ligand binding characteristics of the insulin hexamer
were employed to develop a quantitative model for a symmetry-
asymmetry-based cooperativity mechanism.236 A systematic
analysis of crystal data using Secbase suggests that cooperative
effects which mutually polarize spatially well-aligned hydrogen
bonds are present either in α helices and parallel β sheets,
whereas such influences seem to be lacking in 310 helices and
antiparallel β sheets. Jensen and co-workers developed a
computational methodology for backbone amide proton
chemical shift (δH) predictions based on ab initio quantum
chemical treatment of part of protein G and ubiquitin.170
Hydrogen bond geometry was indicated to be the most
important δH-determinant, besides which longer-range cooper-
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ative effects of extended hydrogen networks were also shown to
make significant contributions to δH. Houk and co-workers
studied the strong reversible binding of biotin by avidin and
streptavidin using DFT and ab initio methods.510 Five hydrogen
bonds were shown to act cooperatively leading to stabilization
that is larger than the sum of individual hydrogen-bonding
energies. Also a charged aspartate was shown to be the key
residue that provides the driving force for cooperativity in the
hydrogen-bonding network for both avidin and streptavidin by
greatly polarizing the urea of biotin. Recently Gibson and co-
workers have captured cooperative interaction data in a
structured format that is backward compatible with PSI-MI
(Proteomics Standards Initiative of the Human Proteome
Organization)-based data and applications.511 Oxyanion holes
commonly found in many enzyme structures are crucial for the
stabilization of high-energy oxyanion intermediates or transition
states through hydrogen bonding.512−517 Site-directed muta-
genesis studies on the catalytic triad, a group of three amino acids
that are found in the active sites of some proteases, reveal the
importance of the oxyanion hole for catalysis.518 Thus, the
importance of cooperativity has been established in the structure
and function of a large number of proteins.438−520
9.3. Drug Receptor Interactions
Williams and co-workers have contributed substantially to
understanding associations between two or more molecules
besides considering the effect of interactions with solvent
molecules and the changes in the internal structure of the
associating molecules on binding.28−30,521−524 Of particular
significance is the study on the cooperativity between binding of
cell wall precursor analogs/ligands to and antibiotic dimerization
of the clinically important vancomycin group antibiotics.523 An
analysis of the origins of a cooperative binding energy of
dimerization illustrates how, when a protein has a loose structure,
the binding energy of another molecule to the protein can derive
in part from changes occurring within the protein. The above-
mentioned result was indeed important for drug design as it is
indeed common practice to seek the origins of binding affinity at
the interface formed between associating entities. An illustration
of how partitioning of binding free energy for each of the
interactions which are made or broken on binding, in particular
for the hydrophobic effect, ignores the associated cooperativity
made by them.29 An exploration of the relationship between
noncovalent structure and free energy of binding was undertaken
to include the roles of enthalpy and entropy of association.
Considering dimerization of vancomycin-type antibiotics pos-
itive cooperativity was shown to manifest itself in a more
favorable enthalpy of association and a partially compensating
less favorable entropy of association.30 The study suggests that
sets of noncovalent interactions that are made with positive
cooperativity must be mutually enhancing in their free-energy
benefits. While conversely, sets of noncovalent interactions that
are made with negative cooperativity must be mutually
weakening in their free-energy benefits.524 Besides, changes in
the relative populations of the monomer and asymmetric dimer
forms of ristocetin A, upon binding of two molecules of ligand,
showed that ligand binding was negatively cooperative with
respect to dimerization.
Several studies have established the role of different non-
covalent interactions in drug receptor interactions observed in
therapeutically important targets.525−546 By use of crystal
structure analysis and isothermal titration calorimetry for a
congeneric series of thrombin inhibitors, Klebe and co-workers
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have shown how extensive cooperative effects between hydro-
phobic contacts and hydrogen bond formation are intimately
coupled via dynamic properties of the formed complexes.525 A
complex picture of mutually competing and partially compensat-
ing enthalpic and entropic effect determined the nonadditivity of
free-energy contributions to ligand binding at the molecular
level. Two separate series of thrombin inhibitors containing
hydrophobic side chains of increasing size that bind in the S3
pocket with or without an adjacent amine that engages in a
hydrogen bond with Gly 216 were studied. The presence of an
adjacent hydrogen bond was shown to enhance binding affinity
per Å2 of hydrophobic contact surface in the S3 pocket by 75%
and 59%, respectively, over the inhibitors lacking this hydrogen
bond.526 This demonstrated cooperativity between the hydro-
phobic interaction and the hydrogen bond. Hangauer and co-
workers have shown water-mediated ligand functional group
cooperativity through a study on four thermolysin phosphona-
midate inhibitors.527 The differential binding free energy and
enthalpy was caused by replacement of a hydrogen with a Me
group, which binds in the well-hydrated S2′ pocket and is more
favorable in the presence of a ligand carboxylate. Klebe and co-
workers have recently shown a surprising nonadditivity of
functional group contributions for the carboxylate and/or methyl
groups in the binding of four congeneric peptide-like
thermolysin inhibitors where the ligands differ only by a terminal
carboxylate and/or methyl group.528
9.4. Protein Folding
A large number of experimental and theoretical studies have
aided in providing valuable insights into understanding the
mechanism of protein folding.55,162,547−597 These include
seminal studies on different limiting mechanisms of protein
folding highlighted by the two main models at the time, the
nucleation-propagation mechanism and the diffusion-collision
model and identification and characterization of protein-folding
pathways and their intermediate states.548 Several subtopics
addressed in this context included proline isomerization, protein
fragments, and disulfide bond intermediates.549 Simulation and
theoretical models have played an important role in shaping the
understanding of protein folding.550 Kinetically distinct pathways
for folding were identified showing that the folding energy
landscape was more complex than had been originally
thought.551 The process of protein folding is characterized by a
high degree of cooperativity manifested by the almost negligible
population levels of partially stable intermediate states observed
during transition between folded and unfolded states.552,553 Dill
et al. suggested a hydrophobic zipper hypothesis to determine
the physical basis of cooperativity by which proteins avoid
exhaustive searching of conformational space.557 Hydrophobic
zipper cooperativity for heteropolymer collapse was shown to be
driven by nonlocal interactions mediated by the solvent leading
to helical, sheet, and irregular structures, depending on the amino
acid sequence. More recently, a theory for protein-folding
stability and cooperativity for helix bundle proteins has also been
suggested by them.558
Chan and co-workers studied protein folding cooperativity by
comparing different theoretical models.55,559−561 On the basis of
simple lattice models, they suggest that proteinlike thermody-
namic cooperativity may require a cooperative interplay between
local and nonlocal interactions.560 Baker and co-workers
reported an important statistical study which proposed that
native state topology, and not sequence itself, was the main
determinant of folding pathways.555 Besides the entropic
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contributions to the folding barrier were found to be
considerable. They subsequently reported the noncooperative
folding behavior of the de novo designed protein Top7, thereby
raising the possibility that evolutionary selection for biological
functions might have led to folding cooperativity.562−564 Plaxco
and co-workers demonstrated that traditional Go̅-potential
polymers in which only inteactions present in the native state
are favorable lack the extreme cooperativity that characterizes the
folding of naturally occurring, two-state proteins.565,566 The
folding rates of a diverse set of Go̅ 27-mers were shown to be
poorly dispersed and effectively uncorrelated with native state
topology. Zhou et al. employed an all-atom off-lattice model of
the fragment B of staphylococcal protein A to suggest that a large
well-packed solid core is the origin of the folding cooperativity of
proteins.567 Thirumalai and co-workers have also probed into the
effect of finite size on cooperativity and the rates of protein
folding using lattice models with side chains, off-lattice Go̅
models, and the available experimental data.568,569
A few recent experimental studies570−573 considering
cooperativity of protein folding are discussed below. Dobson
and co-workers employed hydrogen-exchange experiments
monitored by NMR and mass spectroscopy to reveal the impact
of a specific mutation in human lysozyme, in terms of its ability to
reduce the stability of the beta domain and an adjacent C-helix in
the native structure.571 Further, mass spectroscopy data revealed
the high degree of cooperativity involved in the transient folding
of these regions. Clarke and co-workers have addressed the
apparent cooperativity in the folding of multidomain proteins, in
particular that of pairs of three-helix bundle spectrin domains and
found that it depends on the relative rates of folding of the
constituent domains.572 Equilibrium studies done in the study
indicate that equilibrium data alone are insufficient to describe
the folding of multidomain proteins and to quantify the effects
that one domain can have on its neighbor. Shank and co-workers
have used a single molecule optical tweezers approach to induce
the selective unfolding of particular regions of T4 lysozyme to
investigate how the topological organization of a protein affects
the coupling and folding cooperativity between its domains.573
The study showed that the topological organization of the
polypeptide chain critically determines the folding cooperativity
between domains. Proteins may have evolved to select certain
topologies that increase coupling between regions to avoid areas
of the landscape that lead to misfolding. Gellman and co-workers
have described a 20-residue peptide that adopts a triple-stranded
antiparallel β-sheet conformation in aqueous solution.574 This
model system was used to show that antiparallel β -sheet
formation is cooperative, perpendicular to the strand direction
based on site-specific conformational data from NMR spectros-
copy. Indeed peptide β-sheet systems have emerged as context
independent models for probing secondary structure propen-
sities and aspects of cooperativity both parallel and perpendicular
to the strand direction.575,576 Simmerling and co-workers
performed microseconds of standard- and replica-exchange
MD simulations on designed three-stranded β-sheet structures
to understand cooperativity in their folding.577 Using MD
simulations, Hills et al. demonstrated that the hydrophobic
cooperativity seen in the self-association of a model amyloido-
genic peptide STVIYE was sufficient to allow for nucleation-
dependent polymerization with a pentamer critical nucleus.578
Findings of possible noncooperative, folding have also been
reported.582−585 Two types of downhill folding, one where
certain mutants of λ-repressor behave in a two-state manner near
their transition midpoint and under mildly folding conditions,
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but they can fold downhill under strongly folding conditions, and
second where some proteins can undergo global downhill
folding, which means that the protein always behaves in a one-
state manner for the entire range of experimental conditions,
have been reported.561 The results of a more recent study of a
model oligomer of human islet amyloid polypeptide (hIAPP)
segments explored by means of all-atom MD simulations under
different force fields supports a picture of downhill-like
cooperative assembly of β strands during the fibrillation
process.586 Diehl et al. have developed a biosynthetic approach
to control and probe cooperativity in multiunit biomotor
assemblies by linking molecular motors to artificial protein
scaffolds.587 Cooperative interactions between monomeric
kinesin-1 motors attached to protein scaffolds were shown to
enhance hydrolysis activity and microtubule gliding velocity.
Thus, cooperativity in protein folding has been addressed in
varying model systems of interest.55,162,547−597
9.5. Transcription
Transcription regulation in prokaryotes and eukaryotes is known
to occur through the coordinated action of transcription factors
and DNA.524,598−608 The role of cooperativity in this process has
been investigated by several studies, some of which are
mentioned below. Hammer and co-workers have investigated
the long-range cooperativity between gene regulatory sequences
in prokaryote by reporting that transcription initiation can be
regulated from an operator site placed one to five kilobases
downstream of the promoter and the transcribed gene.601 Zhang
and co-workers developed a method which integrates genome-
wide gene expression data and chromatin immunoprecipitation
(ChIP-chip) data to discover biologically relevant synergistic
interactions between different transcription factors.602 Given any
pair of transcription factors, a novel measure of cooperativity
between two transcription factors based on the expression
patterns of sets of target genes was developed.
9.6. DNA/RNA
Although there has been a substantial emphasis on under-
standing cooperativity in proteins with regard to structure,
stability, and also their binding with other molecules, the extent
of cooperativity both in DNA and RNA molecules has been
analyzed to a much lesser extent.609−620 The binding of
surfactant ions to DNA macromolecules is highly cooperative
due to a hydrophobic effect.609 Mel’nikov et al. have shown on
the level of individual DNAs, that salt-induced unfolding
transition of the globules is largely discrete.609 For the ensemble
average of the DNAs, the transition is discrete with
acetyltrimethylammonium bromide but is continuous with
another cationic surfactant distearyldimethylammonium bro-
mide. The discreteness for the coil−globule transition in the
ensemble of DNAs complexed with the first surfactant is
attributed to the existence of the phase transition in whole over
the bulk solution. The cooperativity of assembly of two nucleic
acid strands is determined by the stacking interactions of
consecutively formed base pairs and by the nature and
conformational properties of the sugar−phosphate backbone.
Leumann and co-workers investigated the dependence of duplex
melting cooperativity between two double helical domains on the
length and the conformational properties of the intervening
sugar−phosphate backbone in a model system.610 They found
that structural communication between two double helical
domains is transferred along the DNA backbone over the
equivalent of about 12−20 backbone units, based on whether
there is a symmetric or asymmetric distribution of the
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anucleosidic units on both strands. Deyà and co-workers
computed the cooperativity energies in two models of Z-
DNA.611 The first model demonstrated how the lone pair−π
interaction and hydrogen bonding reinforce between guanine
and ether, whereas a second model studied the influence of
stacking interaction between the cytosine bases upon the
hydrogen bonds and vice versa. Marek and co-workers
investigated structural and energetic features of model guanine
and xanthine containing DNA quadruplexes.612 Emphasizing the
physicochemical nature of the noncovalent interactions involved,
they established that hydrogen bonding makes the greatest
contribution to the internal stability of the DNA quadruplexes,
whereas the aromatic base stacking and ion coordination terms
which are similar account for the rest. EDA analysis also revealed
how guanine containing structures seemed to benefit from a high
degree of hydrogen bond cooperativity, whereas xanthine-
containing models appeared to be characterized by a more
favorable and cooperative π−π stacking. In a summary on the
design and development of a class of molecular duplexes with
programmable hydrogen-bonding sequences and adjustable
stabilities, Gong has emphasized cooperativity of multiple
hydrogen bonding as one of the most important features
associated with the self-assembly of DNA.613 In a recent study on
DNA-based nanostructures built on a long single-stranded DNA
scaffold known as DNA origamis, an attempt was made to model
the annealing and melting properties of DNA constructions.614
Cooperativity between staples was shown to be critical to
quantitatively explain the folding process of DNA origamis.
Oddershede and co-workers have recently demonstrated the
importance of DNA supercoiling as a factor to enhanced
cooperativity and efficiency of an epigenetic switch operating in
bacteriophage λ.615
Herschlag and co-workers report a direct quantitative measure
of tertiary contact cooperativity in a folded RNA.616 The stability
of an independently folding P4−P6 domain from the
Tetrahymena thermophila group I intron was measured by single
molecule fluorescence resonance energy transfer. An enhance-
ment of P4−P6 stability by 3.2 ± 0.2 kcal/mol as a consequence
of cooperativity between the two tertiary contacts was reported
by them. Strobel and cowokers employed nucleotide analog
interference mapping and mutagenesis to determine the possible
sites for glycine binding and tertiary cooperativity in case of the
glycine riboswitch.617
Chance and co-workers have addressed questions related to
RNA structure by combining chemical denaturation and
hydroxyl radical footprinting methods.579 They determined
unfolding isotherms for each of 26 discrete sites of protection
located throughout the Tetrahymena thermophila group I
ribozyme and showed how intradomain contact and three
interdomain contacts show high cooperativity, indicating that
these contacts exhibit global cooperativity in their folding
behavior. Bevilaqua and co-workers found that the small DNA
hairpins fold in a highly cooperative manner with indirect
coupling, while their RNA counterparts fold in a much less
cooperative fashion and display direct coupling.580 The study
also indicated that folding cooperativity in RNA and DNA is
dependent on position in the helix. Brooks and co-workers have
also shown cooperative and directional folding in the case of
preQ1 Riboswitch aptamer domain using an all atom Go̅ model
simulation.581
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10. ANTICOOPERATIVITY
There are several examples of anticooperative binding in proteins
and in materials.621−630 A combined thermodynamic, kinetic,
and X-ray crystallographic study on ligand-binding properties of
recombinant ferric vitreoscilla homodimeric hemoglobin helped
to establish anticooperative ligand-binding behavior in sol-
ution.621 Anticooperativity was reflected by a 300-fold decrease
in the second-order rate constant for cyanide and imidazole
binding to the monoligated ferric vitreoscilla hemoglobin with
respect to that for ligand association to the ligand free
homodimer in solution. Doig and co-workers studied Glu-Lys
and Lys-Glu salt bridges formed when the residues are spaced i, i
+ 4 in an isolated α-helix in aqueous solution.622 When the side
chains were spaced i, i + 4, i + 8, forming a Glu-Lys-Glu triplet,
the second salt bridge provided no additional stabilization to the
helix. They suggested that the triplet may be less stabilizing than
the sum of the two individual interactions, giving rise to
anticooperativity.
In a study modeling the antigen−antibody encounter, a
formula that enables one to calculate the anticooperativity as a
function of the size of the binding site for any values of the
separation between the two active lobes and of the antigen size
was proposed.623 Liang and co-workers introduced a geometric
model for quantifying 3-body interactions in native proteins.624
The study defined a nonadditive coefficient that characterized
cooperativity and anticooperativity of residue interactions in
native proteins by measuring the deviation of 3-body interactions
from 3 independent pairwise interactions. While comparing the
3-body propensity value from what would be expected if only
pairwise interactions were considered, the study revealed how
hydrophobic interactions and hydrogen-bonding interactions
make nonadditive contributions to protein stability. The
nonadditive nature was shown to depend on whether such
interactions were located in the protein interior or on the protein
surface. In order to explain multibody effects in hydrophobic
association on a molecular level, Czaplewski et al. showed that
the three-methane potential of mean force (PMF) in water at 298
K for their system (i.e., the trimer case with isosceles-triangle
geometry) is anticooperative at the contact minimum.625
Nonadditivity properties of hydrophobic interactions were
shown to be temperature-dependent by Chan and co-work-
ers.55,626 Kudrev developed a method for the mathematical
processing of experimental titration curves of a homogeneous
one-dimensional polynucleotide.627 This method helps in
calculation of the cooperativity and anticooperativity parameters
of the interaction of a ligand with an infinite homogeneous
polymer.
Negative cooperativity has been reported in studies on
regulatory enzymes several decades ago.631−637 While elucidat-
ing negative cooperativity in the case of CTP synthetase, an
allosteric enzyme, Levitzki et al. gave strong support for the
sequential model of subunit interactions which postulates that
ligand-induced conformational changes are responsible for
regulatory and cooperative phenomena in enzymes.631 DeMeyts
et al. reported the characterization of negative cooperativity in
site−site interactions of insulin receptor.632 Crystal structures of
the negatively cooperative aspartate receptor caught at
intermediate stages in the binding process were studied by
Koshland.633 On the basis of frequency of occurrence of
negatively cooperative proteins studied, sequential changes in
binding patterns were shown to be extensive not only in positive
as well as in negatively cooperative proteins but also in those with
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no cooperativity. Employing kinetic analyses and surface
plasmon resonance detection, studies on regulation of tyrosine
hydroxylase by the concentration of tetrahydrobiopterin cofactor
have shown a presence of negative cooperativity in their
binding.634 Using NMR, Stevens et al. report a case of strong
negative cooperativity by delineation of the allosteric mechanism
of a dimeric cytidylyltransferase enzyme between the first and
second binding of its substrate, CTP.635 A role for prion protein
in the function of cell protection by scavenging excess copper has
been suggested by Millhauser and co-workers based on electron
paramagnetic resonance and fluorescence quenching experi-
ments to determine the copper affinity to an N-terminal
octarepeat domain of the protein.636 Decomposition of the
EPR spectra revealed the proportions of all coordination species
throughout the copper concentration range and identified
significant populations of intermediates, consistent with negative
cooperativity. Thus, several salient aspects of cooperativity in
biochemistry have been addressed.
11. MANIFESTATION OF COOPERATIVITY
11. 1. Self-Assembly
Consequences of cooperativity in supramolecular systems have
been exploited for template-directed molecular synthesis,
development of methods to probe weak supramolecular
interactions besides assessing cooperativity in self-assembly
processes.638−689 Meijer and co-workers have studied the role of
cooperativity in supramolecular polymers.640−647 Spectroscopi-
cally monitoring the nucleation process in chemical self-assembly
of π-conjugated molecules leading to formation of helical
supramolecular fibrillar structures revealed the presence of a
remarkably high degree of cooperativity.641 The study also
elucidated a significant role for organized shell of solvent
molecules in rigidifying the aggregates and guiding them toward
further assembly into bundles and gels. In another study, they
demonstrated a balancing out of attractive forces based on dipole
interactions, π−π stacking, solvophobic effects, with electrostatic
repulsive interactions, in the process of self-assembly of discotic
amphiphiles into helical columnar aggregates of controlled
length.642 The presence or absence of cooperativity in the self-
assembly mechanism was determined to be a key feature in
manipulating the physical properties of synthetic supramolecular
polymers. Stoddart and co-workers have assessed the impact of
multivalency and cooperativity in the context of self-assembling
both as models for biological processes and to get a handle on
how to order molecules into complex nanoarchitectures.648,649 In
a recent study on extended π···π stacking between contiguous
arene units in the rings of a series of oligorotaxanes, progressively
enhanced molecular recognition and increased positive cooper-
ativity were shown to be important.649 Studies on m-phenyl-
eneethynylene oligomers demonstrate how critical chain length
phenomena mark the onset of cooperativity in a macromolecule
and indeed how the supramolecular polymerization mechanism
is sensitive to length of the starting oligomer and geometry of the
monomer units.650,651
DFT studies by de Greef and co-workers rationalized
experimentally observed cooperative growth of C3-symmetrical
trialkylbenzene-1,3,5-tricarboxamide supramolecular polymers
that self-assemble into ordered 1D structures through hydrogen
bonding.652 Cooperative growth of these structures was shown
to be due to electrostatic interactions and nonadditive effects
emanating from redistribution of the electron density along the
aggregate length. Hanke and co-workers report an investigation
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of the cooperative effects that control the synthesis of a graphene
nanoribbon on the Au(111) surface starting from an anthracene
polymer while considering the associated van der Waals
interactions using DFT calculations.653 Cooperativity in self-
assembled complexes of twenty-nine homo and hetero metallic
polynuclear triple-stranded helicates is explained by a combina-
tion of experimental synthesis and a simple point-charge model
which fine-tunes the balancing between electrostatic repulsion
and solvation energies. 654 A combined theoretical and
experimental approach to probe weak supramolecular inter-
actions in bisurea solution focuses on evolving a supramolecular
platform that presents a cooperative transition, so that a
perturbation of such a transition can be monitored by a
temperature scanning experiment.655
Waters and co-workers pursued mutagenesis studies in [2]-
catenanes which mimic numerous key properties of large protein
systems.656 Expounding on the role of multivalency and
cooperativity on the structure and stability of these systems
where multiple noncovalent interactions create a web of
interdependent interactions, they demonstrate how changes to
a component of the web leads to compensating effects in some of
the linked interactions. In others, the perturbations result in a
cascade of destabilizing interactions that lead to disproportionate
losses in stability. Ercolani proposed a method to assess
cooperativity in self-assembly processes in the cases of self-
assembly of helicates and of porphyrin ladders and suggested in
contrast that positive cooperativity in artificial self-assembling
systems is probably much more rare than it was previously
thought to be.657 Cooperativity and multivalency have also been
implicated in the case of different kinds of materials like
multipolymers,658 polyethylenimine gels,650 etc. Prohens et al.
have worked on cooperativity in solid state squaramides where
hydrogen-bonded catemers play a crucial role in defining the
solid-state synthon of disecondary squaramides, overriding their
preferred association mode in solution.660 Zhao and co-workers
designed aromatically functionalized oligocholate pore-forming
materials in which the aromatic interactions and hydrophobic
interactions could work cooperatively.661
11. 2. Chelate Cooperativity
Several studies have emerged on the concept of chelate
cooperativity,690−694 which is essentially an increase in binding
affinity due to intramolecular interactions. Hunter et al. have
demonstrated the influence of hydrogen bond strength on
chelate cooperativity using the metalloporphyrin-ligand sys-
tem.690 A systematic survey of the relationship between chemical
structure and cooperativity to measure the free-energy
contributions due to intramolecular ether-phenol hydrogen
bonding in different supramolecular architectures using chemical
double mutant cycles in toluene has been reported. Emphasizing
the role of preorganization in porphyrin oligomer complexes,
Anderson and co-workers demonstrate how a highly cooperative
two-state model describes stabilities of the studied systems.691
Denaturation titrations of complexes of cyclic and linear zinc-
porphyrin hexamer with multidentate ligands reveal that the
stepwise effective molarities for the third through sixth
intramolecular coordination events with the cyclic hexamer are
extremely high compared to linear porphyrin oligomers. Schalley
and co-workers have recently reported the effects of chelate
cooperativity and spacer length on the assembly, thermody-
namics, and kinetics of divalent pseudorotaxanes.692 These
studies indicate how very subtle changes in the spacer length
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cause substantial changes in the magnitude of cooperative
binding as expressed in the large differences in effective molarity.
11. 3. Catalysis
Enzyme catalysis and associated cooperativity has served as an
inspiration for the design of new chemical reactions that proceed
with efficiency, high selectivity, and minimal waste.499,503,695
Recent studies reveal cooperative effects with organocatalysts
used in a wide variety of chemical transformations.696−727 The
emphasis in these studies lies in the demonstration of the precise
control of a cooperatively catalyzed reaction with noncovalent
interactions alone.
Schreiner and co-workers presented a mild and efficient
method for the completely regioselective alcoholysis of styrene
oxides.722 This study suggested a hydrogen-bonding mediated
cooperative Brønsted-acid catalysis mechanism for a system
consisting of a thiourea derivative and mandelic acid. In
subsequent studies, Schreiner and co-workers reported a
thiourea−Brønsted acid cooperative catalytic system for the
enantioselective cyanosilylation of aldehydes.720 Combined
experimental and computational investigations showed that the
key catalytic species resulted from the cooperative interaction of
bifunctional thioureas and an achiral acid that formed well-
defined chiral hydrogen-bonding environments. Jacobsen and
co-workers have conducted extensive studies on the cooperative
mechanisms responsible for stereoinduction in highly enantio-
selective reactions such as the Claisen rearrangement, cationic
polycyclizations, and Strecker reaction promoted by noncovalent
catalysts.696 They also showed how creating cooperative catalysts
lies in controlling the competition of the two catalysts for the
reactants as well as their mutual interaction through the Povarov
reaction using urea and thiourea derivatives.698 Krautwald et al.
have reported studies on α-allylation of branched aldehydes
where two independent catalysts working synergistically allow
the controlled synthesis of all four stereoisomers in a reaction
that forms carbon carbon bonds.699
Martiń and co-workers developed a simple synthetic receptor
that displays an enantioselective positive cooperativity between
intrareceptor interactions and guest binding leading to a
reinforcement of chiral recognition.700 The role of cooperativity
has also been addressed by several other studies on asymmetric
catalysis. Kanai et al. reported the development of Lewis acid
Lewis base bifunctional asymmetric catalysts with an emphasis
on cooperativity specifically for a wide range of enantioselective
reactions including cyanosilylation of aldehydes, Strecker
reaction of aldimines, Reissert reactions of quinolines, isoquino-
lines, and pyridines, cyanosilylation of ketones, and Strecker
reaction of ketoimines.701 Scheidt and co-workers have also
reported how precise orchestration of interactions to activate
reactants simultaneously or sequentially leads to cooperative
catalysis.702 This concept has been clearly shown through a study
on cooperative N-heterocyclic carbene/Lewis acid catalytic
system that promotes the addition of homoenolate equivalents
to hydrazones, generating highly substituted γ-lactams with a
high degree of diastereo- and enantioselectivity. Further studies
based on the approach of cooperative catalysis include a report by
Patil where merging metal and N-heterocyclic carbene catalysis
has been employed as a mode to explore enantioselective organic
transformations.703 Hapiot and co-workers have shown the
implication of cooperativity in explaining the catalytic perform-
ances of cyclodextrin-substituted polymers in aqueous rhodium-
catalyzed hydroformylation of 1-hexadecene.704
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Figure 16. Examples of interplay of noncovalent interactions in the field of material science: (a) in self-assembled nanotubes from flexible macrocycles,
ref 751, (b) in solid-state squaramides, ref 660, and in (c) oligophenyleneethynylene (OPE)-based supramolecular polymer, ref 749.
A recent review by Raynal et al. extensively focuses on
supramolecular catalysts for which the observed catalytic activity
and/or selectivity have been imputed to noncovalent interaction
between the reaction partners.719 Sunoj and co-workers have
explored the mechanistic insights on cooperative catalysis
through computational quantum chemical methods.718 Cooper-
ative catalysis addressed in this review cover multicatalytic
approaches under one pot reaction conditions, wherein the
complementary attributes of two or more catalysts are made to
work together. Metal−ligand cooperativity may lower kinetic
barriers and enable unique reaction chemistry specifically in the
case of cleavage of N−N bonds by soluble transition metal
complexes. On the basis of this concept, Chirik and co-workers
have prepared early transition metal analogs to exploit metal−
ligand cooperativity in reactions relevant to nitrogen fixation.705
Messerle and co-workers have reported studies on homobime-
tallic dirhodium and diiridium complexes as catalysts for the
intramolecular dihydroalkoxylation of a series of alkyne diol
substrates.706 The enhanced activity and selectivity of bimetallic
catalysts as against a single metal catalyst was attributed to
cooperativity between the metal pairs, and a bimetallic
intermediate for the reaction pathway is proposed. Motta et al.
have also reported the distinctive center-to-center cooperative
catalytic properties exhibited by bimetallic constrained geometry
catalysts (CGCs) and analyzed the impact of metal−metal
proximity effects on ethylene polymerization processes using
DFT calculations.707 Mankad and co-workers showed that
catalytic C−H borylation, a transformation that previously
required noble metal catalysts, could be achieved with base metal
catalysts by using a mechanistic paradigm that depends on
intimate cooperativity between two closely associated yet distinct
base metal sites.708,709
Besides, studies on a supramolecular system that is based on
cooperative self-assembled helicity, exhibiting strong chiral
amplification and having racemization and deracemization
processes in thermodynamic equilibrium have also been
reported.710 Fitz et al. have focused on the intermolecular
cooperativity of reactive polymers considering epoxy amine
model systems for their case study.711 The molecular level
characteristics that govern the intermolecular cooperativity of
these reactive systems were determined on one hand by
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Review
molecular symmetry, rigidity, and steric hindrance and on the
other by the type and concentration of all dielectrically active
species. Both molecular and dielectric architecture were observed
to vary in the course of the chemical reaction, with the overall
direction in which the cooperativity shifts being governed by the
interplay between these two phenomena. The role of interplay
between CH−π and CF−π interactions in determining the
structure of N-heterocyclic carbene (NHC) palladium com-
plexes proven to be effective catalysts in many important
reactions, especially cross-coupling reactions, was demonstrated
using 1H NMR spectroscopy, X-ray crystallography, and DFT
calculations.712 Thus, several studies performed in recent years
underline the contemporary relevance of cooperativity in the
design of catalysts whose mode of action is governed by
cooperativity.696−727
11. 4. Material Science
The impact of different noncovalent interactions on materials has
been highlighted through several recent studies.728−736 Some
examples of interplay of noncovalent interactions in the field of
material science are shown in Figure 16. Design of several
bioinspired novel materials in the recent years has emphasized
the role played by cooperativity of multiple noncovalent
interactions especially that of the hydrogen bond.737,738 Welland
and co-workers have shown a scalable self-assembly approach to
making free-standing films from amyloid protein fibrils, wherein
the films were well-ordered and highly rigid, with a Young’s
modulus which is comparable to the highest values for
proteinaceous materials found in nature.739 Buehler has
demonstrated how understanding self-assembly of amyloid
proteins can be exploited to make well-ordered and strong
functional macroscopic materials.740 The presence of hydrogen
bonds in β sheet structures under nanoconfinement shows how a
weakness can be turned into a strength. On the basis of a study of
the shearing deformation of hydrogen bonds within β-strands
and β-sheet nanocrystals applying an elastic structural model, the
number of hydrogen bonds that deform cooperatively was
identified. The studies of Buehler and co-workers740−745 further
emphasize how the intrinsic strength limitation of hydrogen
bonds can be overcome by the formation of a nanocomposite
structure of hydrogen bond clusters, thereby enabling the
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formation of larger and much stronger beta-sheet structures.741
Besides the nanoscale organization of hydrogen bonds was
shown to be critical for the mechanical behavior of protein
materials such as silk.742 More recently, they have also analyzed
the size of region in which hydrogen bond deformation in
functional groups attached to carbon nanotubes (CNT) is
cooperative, focusing specifically on CNTs functionalized with
carboxyl groups as a model system.743 These studies reveal that
the effect of structural organization of functional groups is
significant not only in very small diameter CNTs but also in
larger diameter CNTs which are most commonly used for
engineering applications. Larger diameter CNTs show a larger
cooperative deformation range, providing a good basis for further
improvement by adding structured functional groups. Tuning
the water content in graphene oxide paper nanocomposites was
shown to allow for the translation of the nanoscale hydrogen
bond network into macroscale mechanical properties.744 For
graphene oxide paper at an optimal concentration of water, the
degree of cooperative hydrogen bonding within the network
comprising adjacent nanosheets and water molecules was found
to enhance the modulus of the paper. Hu et al. have employed a
scalable strategy to produce biomimic continuous fibers with
brick and mortar structures of alternating graphene sheets and
hyperbranched polyglycerol (HPG) binders via wet-spinning
assembly technology.746 The resulting macroscopic supra-
molecular fibers exhibit excellent mechanical properties
comparable to bone or nacre. The study also provides evidence
of the role played by strong cooperative hydrogen bonding
among adjacent HPGs upon different thickness of HPG-
enveloped graphene sheets. A strategy based on the idea that
incorporation of a perfluorophenyl group as the end-capped π-
conjugated part, and a linking amino acid of phenylalanine with a
phenyl moiety in the side chain, forms a new intramolecular
building block in a peptide hydrogelator considering the efficient
formation of supramolecular nanofibers and hydrogels was
recently established.747
Yam and co-workers have employed a series of luminescent
metallogels of PtII terpyridyl complexes showing gelation
properties driven by an interplay between Pt···Pt and π−π
interactions in addition to hydrophobic−hydrophobic inter-
actions.396 Schneider and co-workers studied the impact of
cooperativity and selectivity in chemomechanical polyethyleni-
mine gels.659 The gel particles obtained from polyethylenimine
(PEI) cross-linked with 10% ethylene glycol diglycidyl ether
demonstrated a considerable selectivity in size changes on
exposure to solutions of different effector compounds. A striking
cooperativity was noted if aromatic compounds such as
naphthoic acid were used simultaneously with amino acids as
effectors. Miravet and co-workers highlighted the key role played
by solubility in influencing the gelation process.748 A model to
relate thermal stability and minimum gelation concentration
values of small-molecule gelation in terms of the solubility and
cooperative self-assembly of gelator building blocks was
developed.
Fernández and co-workers have recently reported an
oligophenyleneethynylene (OPE)-based amphiphilic PtII com-
plex that forms supramolecular polymeric structures in aqueous
and polarmedia driven by π−π and different weak C−H···X (X =
Cl, O) interactions involving chlorine atoms attached to the PtII
centers as well as oxygen atoms and polarized methylene groups
belonging to the peripheral glycol chains.749 By employing a
collection of experimental techniques, self-assembly and hydro-
gelation triggered by cooperative π−π and unconventional C−
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Review
H···X hydrogen-bonding interactions was demonstrated. A novel
method for fabricating tough hydrogels that are totally physically
cross-linked by cooperative hydrogen bonding between a pre-
existing polymer and an in situ polymerized polymer was recently
reported by Fang and co-workers.750 Comparative synthesis
experiments, DSC characterization, and molecular modeling
indicated that the formation of strong cooperative hydrogen
bonding between the pre-existing poly(N-vinylpyrrolidone) and
the in situ formed P-aqueous acrylamide chains contributes to
the gel formation and the toughening of the hydrogels.
Martiń and co-workers have reported crystal structures of self-
assembled nanotubes through stacking of macrocycles.751 A
combination of assembly driven by the propensity of the
macrocycles to create nearly flat structures displaying a void
space within them and the cooperativity of weak directional
interactions such as dipole−dipole interactions and CH···O
hydrogen bonds and nondirectional interactions such as van der
Waals contacts resulted in yielding unexpected self-assembled
nanotubes. Tokmachev et al. conducted an analysis of all
hydrogen bond networks for finite elements of ice nanotubes
formed by up to 32 water molecules.752 The hydrogen bonds in
the growing ice nanotubes were classified according to their
structural positions and significant dependencies on the
cooperativity energy, and bond lengths on the system’s
morphology were revealed. Ju and co-workers recently reported
the binding affinity and thermodynamic parameters between a
surfactant and carbon nanotube using flavin mononucleotide-
wrapped carbon nanotubes as model systems.753 The binding
affinity of metallic tubes was weaker than that of semiconducting
tubes, and equilibrium constant patterns from semiconducting
tubes showed a preference to certain SWNT chiralities and
surfactant-specific cooperativity according to nanotube chirality.
Jin et al. have reported the self-assembly of a gemini-shaped,
chiral amphiphilic hexa-perihexabenzocoronene having two
chiral oxyalkylene side chains, along with two lipophilic side
chains, yielding graphitic nanotubes with one-handed helical
chirality.754 A high level of chirality amplification observed
therein indicated a long-range cooperativity in the self-
assembling process.
The role of dipolar interactions and hydrogen-bonding
interactions in fine-tuning the linear and first nonlinear optical
(NLO) responses in molecular aggregates were investigated by
Pati and co-workers.755 The nonadditivity of optical properties in
their systems were shown to arise specifically due to cooperativity
of weak interactions. Calculations performed on model systems
starting from dimers to multiple aggregates provide insights into
the interaction mechanisms and strategies to enhance the first
hyperpolarizabilities of π-conjugated molecular assemblies.
Overney and co-workers have studied a second-order nonlinear
optical material of a class of self-assembling molecular glasses
involving quadrupolar phenyl-perfluorophenyl (Ph-PhF) inter-
actions by analyzing its molecular relaxation phenomena and
phase behavior using a nanoscale methodology based on
scanning probe microscopy.756 The mesoscale dynamics and
cooperativity involved in relaxation processes were captured and
quantified in terms of dynamic entropy and enthalpy. The
importance of entropic cooperativity in the design of novel
materials that entail a multitude of interactive constraints form
dipole field interactions to local dendritic bonding have also been
studied by analyzing a wide-range of dendritic organic NLO self-
assembly molecular glasses.757 Suponitsky et al. have explored
the effect of π···π stacking aggregation on hyperpolarizability in
the context of supramolecular design of NLO materials.758 They
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showed cases of positive cooperativity and more frequently cases
of negative cooperativity. A decomposition approach was
employed to analyze the reasons of deviation of aggregate
molecular hyperpolarizability from additivity as well as the
cooperative effect of intermolecular interactions on hyper-
polarizability for stacks of growing size. Mafé and co-workers
proposed a nanoscale switch, giving a nonlinear function with
two conductive states separated by a sharp transition region on
the basis of an array of molecular dipoles.759 Employing
theoretical calculations, they revealed that the local interactions
between dipoles result in cooperative phenomena that can
significantly improve the switching characteristics.
Pettersson and co-workers examined the balance of surface
bonding and hydrogen bonding in the mixed OH + H2O
overlayer on Pt(111), Cu(111), and Cu(110) using DFT
calculations.144 A cooperativity effect between surface bonding
and hydrogen bonding that underlies the stability of the mixed
phase at metal surfaces was noted. Water molecules become
more strongly bonded to the surface upon hydrogen bonding to
OH, while the OH surface bonding is instead weakened through
hydrogen bonding to water. Jones and co-workers have explored
mechanisms to tune cooperativity between aminoalkylsilanes
and silanols on a silica surface by varying the length of the alkyl
linker attaching the amine to the silica surface from methyl to
pentyl.760 The linker length was shown to strongly affect the
catalytic cooperativity of amines and silanols in aldol
condensations as well as the adsorptive cooperativity for CO2
capture. Bouteiller et al. studied the role played by high
cooperativity in the thickness transition of a rigid supramolecular
polymer made from low molecular weight bisurea.761 Self-
assembly by hydrogen bonding into two distinct high molecular
weight structures revealed the tunability of this transition. Jain
and co-workers have very recently found evidence of atomic level
cooperativity in an inorganic material.762 A thousand-atom
nanocrystal of the inorganic solid cadmium selenide exhibits
strong positive cooperativity in its reaction with copper ions. A
nanocrystal doped with a few copper impurities becomes highly
prone to be doped even further, as manifested by a strongly
sigmoidal response in optical spectroscopy and electron
diffraction measurements.
Wu and co-workers investigated the adsorption and surface
forces due to multivalent polymers based on coarse-grained
polymer models.658 Polymers with multiple binding segments
exhibit strong cooperativity by providing higher levels of surface
protection than those with only one binding site. Negative
cooperativity was observed for an architecture with weakly
attractive anchoring segments. Gröhn and co-workers have very
recently reported the formation of a new type of organic−
inorganic hybrid particle with tunability of particle size, through
self-assembly driven by the interplay of three noncovalent
interactions namely ionic, π−π, and Hamaker interactions.763
Hamaker interactions are van-der-Waals interactions on the
colloidal scale. This is a short-range force that in a diluted system
can only come into play once particles are brought close to each
other through other forces. Gibbs-Davis and co-workers have
studied the influence of gap length on cooperativity and rate of
association in DNA-modified gold nanoparticle aggregates.764
The flexibility in aggregates decreases the rate of aggregation as
well as the extent of cooperativity, suggesting implications in
genomic DNA detection. Thus, a substantial number of studies
including the above-mentioned specific examples clearly
illustrate the relevance and importance of cooperativity among
noncovalent interactions in wide-ranging novel materials.765−772
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12. PROSPECTS AND OUTLOOK
The current review on cooperativity in noncovalent interactions
elucidates the broad range of fields as diverse as structural
biology, supramolecular chemistry, and material science, etc. to
be influenced by the subtle modulation and amplification of
different noncovalent interactions. Indeed, the search for
quantitative aspects of cooperative effects have added a new
level of complexity and thus reactivated the well-developed field
of noncovalent interactions. We have attempted to show the
topological and structure-oriented factors considered in the
study of noncovalent interactions and also in analysis of
cooperativity as a function of interaction. Cooperativity and
anticooperativity in life sciences in general and in biochemistry in
particular is an old concept. However, there are several new
aspects of biology unfolding such as DNA origami, temporal
cooperativity, etc., and all of them have a role in which
noncovalent interactions influence each other. A number of
instances in catalysis and also materials where structure,
property, and function are critically dependent on the
cooperativity of noncovalent interactions have emerged.
The contribution of theoretical chemistry and electronic
structure theory are phenomenal in understanding the molecular
structure and function. Linking the molecules with the clusters of
various length scales all the way to bulk properties warrants a
detailed qualitative and quantitative understanding on the way in
which the noncovalent interactions manifest themselves. Thus,
in this direction, “How a pair of noncovalent interactions
mutually influence themselves?” remains a question of prime
significance. Such an understanding is necessary to develop
accurate methods to model macromolecular structures and
supramolecular assemblies, which are prevalent in both material
science and biology. Recent years have seen rapid experimental
advances in the design of supramolecular assemblies, smart
materials, catalysts, and biomolecules where noncovalent
interactions play a prominent role. Experiment and theory
have been the two important paradigms since the inception of
science. Upon the spectacular emergence of computer hardware
and software, equations based on theory, which are prohibitive to
solve manually, have given rise to computational sciences or
modeling, and this has become the third paradigm in science. In
the last couple of decades, data intensive research based on
informatics has gained outstanding significance and emerged as
the fourth paradigm of science.773−775 Thus, in contemporary
science, it has become indispensable to integrate the conven-
tional paradigms of “experiment” and “theory” with the modern
paradigms of “modeling” and “informatics” to solve problems in
chemistry along with its interdisciplinary subjects. Rigorous
theoretical understanding is needed also to develop more robust
multiscale modeling approaches. It appears that theoretical
understanding of how various noncovalent interactions manifest
themselves in supramolecular assemblies is rather vague. While
methods based on molecular dynamics give an excellent
dynamics picture it needs to be backed by highly reliable and
accurate first-principles computations. Cooperativity as a
concept is extensively employed across various disciplines and
in slightly varying contexts as has been explained in the review.
There is an underlying need to develop vigorous procedures to
quantitatively determine the extent of cooperativity. However,
quantitative estimation of coopeativity effect is challenging both
computationally and experimentally as the size of the system
increases. First priniciples calcualtions have limitations when the
size of the systems become more than a few hundred molecules,
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Chemical Reviews
and the empirical and other approximate methods are rather
unreliable. The qualitative models developed so far have
limitations to estimate the effect of cooperativity in multimeric
systems. Similarly, the terms anticooperativity and negative
cooperativity need to be used cautiously. We believe more
rigorous models need to be evolved and recommend the use of
anticooperativity in place of negative cooperativity in literature. It
is important to develop both qualitative and quantitative models
of cooperativity and anticoopertivity at the molecular level. As it
is apparent now, the number of empirical evidence emerging in
the areas of chemistry, material science, and biology based on
cooperativity is increasing at a rapid pace. This vast and varied
information coming out of a number of observations needs to be
put together and informatics based approaches need to be
employed in understanding and prediction of new materials.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gnsastry@gmail.com.
Notes
The authors declare no competing financial interest.
Biographies
A. Subha Mahadevi has obtained her Bachelor’s degree from Nizam
College, Osmania University, and her Masters degree in Biotechnology
from University of Hyderabad in 1998. After a gap of 9 years, she
pursued the advanced course in bioinformatics at CSIR-IICT,
Hyderabad, which triggered her interest in the field of computational
biology. She joined the Molecular Modeling Group at IICT in 2008 and
has been awarded the DST Woman Scientist Fellowship in 2010. She
has obtained her Ph.D in Bioinformatics under the guidance of Dr G. N.
Sastry. Her research interests include understanding the role of
noncovalent interactions such as cation-π, stacking and hydrogen
bonding in molecular clusters, supramolecular assemblies, and their
cooperativity.
G. Narahari Sastry has obtained his early education in Andhra Pradesh,
Bachelor’s and Master’s degrees from Osmania University before
obtaining his Ph.D. from the University of Hyderabad under the
supervision of Professor E. D. Jemmis. After a couple of post doctoral
stints with Professor Sason Shaik and Professor Thomas Bally, he started
his independent career in 1997 from Pondicherry University. In 2002, he
moved to the CSIR-IICT, Hyderabad, to head the Molecular Modeling
Group. He has wide ranging research interests in computational
chemistry and computational biology. The focus of the group currently
is on understanding the way in which nonbonding interactions operate
in chemical and biological systems with special attention to cation−π
and π−π interactions. He was awarded the Shanti Swarup Bhatnagar
Award in Chemical Sciences for the year 2011. He has published over
255 scientific papers and is a fellow of the Indian Academy of Sciences,
Andhra Pradesh Academy of Sciences, and also the National Academy of
Sciences, India. He is currently a J.C. Bose National Fellow.
ACKNOWLEDGMENTS
We acknowledge the liberal financial support from CSIR 12th
Five Year Plan, GENESIS, and INTELCOAT as well as from
DST, DBT, and DAE-BRNS. We also thank many of our co-
workers who participated in the studies related to noncovalent
interactions over many years.
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REFERENCES
(1) Pauling, L. The Nature of the Chemical Bond and the Structure of
Molecules and Crystals: An Introduction to Modern Structural Chemistry;
Cornell University Press: New York, 1960.
(2) van der Waals, J. D. Over de Continuı̈teit van den Gas- en
Vloeistoftoestand (On the continuity of the gaseous and liquid state).
Ph.D. Dissertation, University of Leiden, 1873.
(3) Kollman, P. A. Noncovalent Interactions. Acc. Chem. Res. 1977, 10,
365−371.
(4) Müller-Dethlefs, K.; Hobza, P. Noncovalent Interactions: A
Challenge for Experiment and Theory. Chem. Rev. 2000, 100, 143−167.
(5) Riley, K. E.; Pitoňaḱ , M.; Jurečka, P.; Hobza, P. Stabilization and
Structure Calculations for Noncovalent Interactions in Extended
Molecular Systems Based on Wave Function and Density Functional
Theories. Chem. Rev. 2010, 110, 5023−5063.
(6) Mati, I. K.; Cockroft, S. L. Molecular Balances for Quantifying
Noncovalent Interactions. Chem. Soc. Rev. 2010, 39, 4195−4205.
(7) Schalley, C. Analytical Methods in Supramolecular Chemistry; Wiley-
VCH: Weinheim, 2007; p 1.
(8) Atwood, J. L.; Barbour, L. J.; Jerga, A.; Schottel, B. L. Guest
Transport in a Nonporous Organic Solid via Dynamic van der Waals
Cooperativity. Science 2002, 298, 1000−1002.
(9) Wagner, J. P.; Schreiner, P. R. London Dispersion in Molecular
Chemistry-Reconsidering Steric Effects. Angew. Chem., Int. Ed. 2015, 54,
12274−12296.
(10) Frank, H. S.; Wen, W. Y. Structural Aspects of Ion-Solvent
Interaction in Aqueous Solutions: A Suggested Picture of Water
Structure. Discuss. Faraday Soc. 1957, 24, 133−140.
(11) Huyskens, P. L. Factors Governing the Influence of a First
Hydrogen Bond on the Formation of a Second One by the Same
Molecule or Ion. J. Am. Chem. Soc. 1977, 99, 2578−2582.
(12) Elrod, M. J.; Saykally, R. J. Many-Body Effects in Intermolecular
Forces. Chem. Rev. 1994, 94, 1975−1999.
(13) Prins, L. J.; Reinhoudt, D. N.; Timmerman, P. Noncovalent
Synthesis Using Hydrogen Bonding. Angew. Chem., Int. Ed. 2001, 40,
2382−2426.
(14) Mahadevi, A. S.; Sastry, G. N. Cation-π Interaction: Its Role and
Relevance in Chemistry, Biology, and Material Science. Chem. Rev.
2013, 113, 2100−2138.
(15) Ma, J. C.; Dougherty, D. A. The Cation-π Interaction. Chem. Rev.
1997, 97, 1303−1324.
(16) Reddy, A. S.; Sastry, G. N. Cation [M = H+, Li+, Na+, K+, Ca2+,
Mg2+, NH4+, and NMe4+] Interactions with the Aromatic Motifs of
Naturally Occurring Amino Acids: A Theoretical Study. J. Phys. Chem. A
2005, 109, 8893−8903.
(17) Reddy, A. S.; Sastry, G. M.; Sastry, G. N. Cation-Aromatic
Database. Proteins: Struct., Funct., Genet. 2007, 67, 1179−1184.
(18) Kim, K. S.; Tarakeshwar, P.; Lee, J. Y. Molecular Clusters of π-
Systems: Theoretical Studies of Structures, Spectra, and Origin of
Interaction Energies. Chem. Rev. 2000, 100, 4145−4185.
(19) Staffilani, M.; Hancock, K. S. B.; Steed, J. W.; Holman, K. T.;
Atwood, J. L.; Juneja, R. K.; Burkhalter, R. S. Anion Binding within the
Cavity of π-Metalated Calixarenes. J. Am. Chem. Soc. 1997, 119, 6324−
6335.
(20) Fairchild, R. M.; Holman, K. T. Selective Anion Encapsulation by
a Metalated Cryptophane with a π-Acidic Interior. J. Am. Chem. Soc.
2005, 127, 16364−16365.
(21) Schottel, B. L.; Chifotides, H. T.; Dunbar, K. R. Anion-π
interactions. Chem. Soc. Rev. 2008, 37, 68−83.
(22) Frontera, A.; Quiñonero, D.; Deyà, P. M. Cation−π and anion−π
interactions. WIREs Comput. Mol. Sci. 2011, 1, 440−459.
(23) Frontera, A.; Gamez, P.; Mascal, M.; Mooibroek, T. J.; Reedijk, J.
Putting Anion−π Interactions into Perspective. Angew. Chem., Int. Ed.
2011, 50, 9564−9583.
(24) Li, Q.; Li, R.; Liu, Z.; Li, W.; Cheng, J. Interplay between Halogen
Bond and Lithium Bond in MCN-LiCN-XCCH (M = H, Li, and Na; X =
Cl, Br, and I) Complex: The Enhancement of Halogen Bond by a
Lithium Bond. J. Comput. Chem. 2011, 32, 3296−3303.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(25) Lu, Y.; Liu, Y.; Li, H.; Zhu, X.; Liu, H.; Zhu, W. Energetic Effects
between Halogen Bonds and Anion-π or Lone Pair-π Interactions: A
Theoretical Study. J. Phys. Chem. A 2012, 116, 2591−2597.
(26) Hunter, C. A.; Anderson, H. L. What is Cooperativity? Angew.
Chem., Int. Ed. 2009, 48, 7488−7499.
(27) Hughes, A. D.; Anslyn, E. V. A Cationic Host Displaying Positive
Cooperativity in Water. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 6538−
6543.
(28) Williams, D. H.; Westwell, M. S. Aspects of Weak Interactions.
Chem. Soc. Rev. 1998, 27, 57−63.
(29) Williams, D. H.; Bardsley, B. Estimating Binding Constants − The
Hydrophobic Effect and Cooperativity. Perspect. Drug Discovery Des.
1999, 17, 43−59.
(30) Calderone, C. T.; Williams, D. H. An Enthalpic Component in
Cooperativity: The Relationship between Enthalpy, Entropy, and
Noncovalent Structure in Weak Associations. J. Am. Chem. Soc. 2001,
123, 6262−6267.
(31) Bissantz, C.; Kuhn, B.; Stahl, M. A Medicinal Chemist’s Guide to
Molecular Interactions. J. Med. Chem. 2010, 53, 5061−5084.
(32) Rodriguez-Docampo, Z.; Pascu, S. I.; Kubik, S.; Otto, S.
Noncovalent Interactions within a Synthetic Receptor Can Reinforce
Guest Binding. J. Am. Chem. Soc. 2006, 128, 11206−11210.
(33) Goyon, J.; Colin, A.; Ovarlez, G.; Ajdari, A.; Bocquet, L. Spatial
Cooperativity in Soft Glassy Flows. Nature 2008, 454, 84−87.
(34) Boyer, P. D. Energy, Life, and ATP. Angew. Chem., Int. Ed. 1998,
37, 2296−2307.
(35) Zhong, Z.; Li, X.; Zhao, Y. Enhancing Binding Affinity by the
Cooperativity between Host Conformation and Host-Guest Inter-
actions. J. Am. Chem. Soc. 2011, 133, 8862−8865.
(36) Carrillo, R.; Morales, E. Q.; Martín, V. S.; Martín, T. A Novel
Approach for the Evaluation of Positive Cooperative Guest Binding:
Kinetic Consequences of Structural Tightening. Chem. - Eur. J. 2013, 19,
7042−7048.
(37) Hasenknopf, B.; Lehn, J. M.; Kneisel, B. O.; Baum, G.; Fenske, D.
Self-Assembly of a Circular Double Helicate. Angew. Chem., Int. Ed. Engl.
1996, 35, 1838−1840.
(38) Lehn, J. M. Toward Complex Matter: Supramolecular Chemistry
and Self-organization. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 4763−
4768.
(39) Hussain, M. A.; Soujanya, Y.; Sastry, G. N. Evaluating the Efficacy
of Amino Acids as CO2 Capturing Agents: A First Principles
Investigation. Environ. Sci. Technol. 2011, 45, 8582−8588.
(40) Higashibayashi, S.; Onogi, S.; Srivastava, H. K.; Sastry, G. N.; Wu,
Y.-T.; Sakurai, H. Stereoelectronic Effect of Curved Aromatic
Structures: Favoring the Unexpected Endo Conformation of Benzylic-
Substituted Sumanene. Angew. Chem., Int. Ed. 2013, 52, 7314−7316.
(41) Umadevi, D.; Sastry, G. N. Molecular and Ionic Interaction with
Graphene Nanoflakes: A Computational Investigation of CO2, H2O, Li,
Mg, Li+, and Mg2+ Interaction with Polycyclic Aromatic Hydrocarbons.
J. Phys. Chem. C 2011, 115, 9656−9667.
(42) Schuster, P.; Wolschann, P. Hydrogen Bonding: From Small
Clusters to Biopolymers. Monatsh. Chem. 1999, 130, 947−960.
(43) Cruzan, J. D.; Braly, L. B.; Liu, K.; Brown, M. G.; Loeser, J. G.;
Saykally, R. J. Quantifying Hydrogen Bond Cooperativity in Water:
VRT Spectroscopy of the Water Tetramer. Science 1996, 271, 59−62.
(44) Stone, A. J. The Theory of Intermolecular Forces, 2 ed.; Oxford
University Press, 2013.
(45) Jorgensen, W. L.; Pranata, J. Importance of Secondary
Interactions in Triply Hydrogen Bonded Complexes: Guanine-Cytosine
vs Uracil-2,6-Diaminopyridine. J. Am. Chem. Soc. 1990, 112, 2008−
2010.
(46) Jorgensen, W. L.; Severance, D. L. Chemical Chameleons:
Hydrogen Bonding with Imides and Lactams in Chloroform. J. Am.
Chem. Soc. 1991, 113, 209−216.
(47) Pranata, J.; Wierschke, S. G.; Jorgensen, W. L. OPLS Potential
Functions for Nucleotide Bases. Relative Association Constants of
Hydrogen Bonded Base Pairs in Chloroform. J. Am. Chem. Soc. 1991,
113, 2810−2819.
2807
Review
(48) Uchimaru, T.; Korchowiec, J.; Tsuzuki, S.; Matsumura, K.;
Kawahara, S. Importance of Secondary Electrostatic Interactions in
Hydrogen-Bonding Complexes: An Investigation Using the Self-
Consistent Charge and Configuration Method for Subsystems. Chem.
Phys. Lett. 2000, 318, 203−209.
(49) Kawahara, S.; Taira, K.; Uchimaru, T. Hydrogen Bond
Cooperativity Derived from Neighboring Hydrogen Bond Formation:
Case Study in Three Iso-Complexes of C8H9N5O2. Chem. Phys. 2003,
290, 79−83.
(50) Jeong, K.-S.; Tjivikua, T.; Rebek, J., Jr. Relative Hydrogen-
Bonding Affinities of Imides and Lactams. J. Am. Chem. Soc. 1990, 112,
3215−3217.
(51) Clark, S. L.; Hammond, P. T. The Role of Secondary Interactions
in Selective Electrostatic Multilayer Deposition. Langmuir 2000, 16,
10206−10214.
(52) Searle, M. S.; Williams, D. H. The Cost of Conformational Order:
Entropy Changes in Molecular Associations. J. Am. Chem. Soc. 1992,
114, 10690−10697.
(53) Searle, M. S.; Sharman, G. J.; Groves, P.; Benhamu, B.;
Beauregard, D. A.; Westwell, M. S.; Dancer, R. J.; Maguire, A. J.; Try,
A. C.; Williams, D. H. Enthalpic (Electrostatic) Contribution to the
Chelate Effect: A Correlation between Ligand Binding Constant and a
Specific Hydrogen Bond Strength in Complexes of Glycopeptide
Antibiotics with Cell Wall Analogues. J. Chem. Soc., Perkin Trans. 1 1996,
1, 2781−2786.
(54) Murphy, K. P.; Xie, D.; Thompson, K. S.; Amzel, L. M.; Freire, E.
Entropy in Biological Binding Processes: Estimation of Translational
Entropy Loss. Proteins: Struct., Funct., Genet. 1994, 18, 63−67.
(55) Moghaddam, M. S.; Shimizu, S.; Chan, H. S. Temperature
Dependence of Three-Body Hydrophobic Interactions: Potential of
Mean Force, Enthalpy, Entropy, Heat Capacity, and Nonadditivity. J.
Am. Chem. Soc. 2005, 127, 303−316.
(56) Chandler, D. Interfaces and the Driving Force of Hydrophobic
Assembly. Nature 2005, 437, 640−647.
(57) Dill, K. A. Dominant Forces in Protein Folding. Biochemistry
1990, 29, 7133−7155.
(58) Ludwig, R. Water: From Clusters to the Bulk. Angew. Chem., Int.
Ed. 2001, 40, 1808−1827.
(59) Steiner, T. The Hydrogen Bond in the Solid State. Angew. Chem.,
Int. Ed. 2002, 41, 48−76.
(60) Grabowski, S. J. What Is the Covalency of Hydrogen Bonding?
Chem. Rev. 2011, 111, 2597−2625.
(61) Ball, P. Water as an Active Constituent in Cell Biology. Chem. Rev.
2008, 108, 74−108.
(62) Grabowski, S. J. Hydrogen Bonding. New Insights; Springer:
Heidelberg, 2006.
(63) Hobza, P.; Havlas, Z. Blue-Shifting Hydrogen Bonds. Chem. Rev.
2000, 100, 4253−4264.
(64) Mahadevi, A. S.; Sastry, G. N. Computational Approaches
Towards Modeling Finite Molecular Assemblies: Role of cation-π, π-π
and hydrogen bonding interactions. In Practical Aspects of Computational
Chemistry I: An Overview of the Last Two Decades and Current Trends;
Leszczynski, J., Shukla, M. K., de Rode, H., Eds.; Springer: The
Netherlands, 2012; p 517.
(65) Turi, L.; Dannenberg, J. J. Molecular Orbital Studies of Crystal
Formation: The Aggregation and Nucleation of 1, 3-Diones. J. Phys.
Chem. 1992, 96, 5819−5824.
(66) Turi, L.; Dannenberg, J. J. Molecular Orbital Study of Acetic Acid
Aggregation. 1. Monomers and Dimers. J. Phys. Chem. 1993, 97, 12197−
12204.
(67) Dannenberg, J. J.; Rios, R. Theoretical Study of the Enolic Forms
of Acetylacetone. How Strong Is the H-Bond? J. Phys. Chem. 1994, 98,
6714−6718.
(68) Morokuma, K.; Pedersen, L. Molecular-Orbital Studies of
Hydrogen Bonds. An Ab Initio Calculation for Dimeric H20. J. Chem.
Phys. 1968, 48, 3275−3282.
(69) Kollman, P. A.; Allen, L. C. Theory of the Hydrogen Bond:
Electronic Structure and Properties of the Water Dimer. J. Chem. Phys.
1969, 51, 3286−3293.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(70) Hankins, D.; Moskowitz, J. W.; Stillinger, F. H. Water Molecule
Interactions. J. Chem. Phys. 1970, 53, 4544−4554.
(71) Keutsch, F. N.; Cruzan, J. D.; Saykally, R. J. The Water Trimer.
Chem. Rev. 2003, 103, 2533−2577.
(72) Buck, U.; Ettischer, I.; Melzer, M.; Buch, V.; Sadlej, J. Structure
and Spectra of Three-Dimensional (H2O)n Clusters, n = 8, 9, 10. Phys.
Rev. Lett. 1998, 80, 2578−2581.
(73) Wernet, Ph.; Nordlund, D.; Bergmann, U.; Cavalleri, M.; Odelius,
M.; Ogasawara, H.; Näslund, L. Å.; Hirsch, T. K.; Ojamäe, L.; Glatzel, P.;
Pettersson, L. G. M.; Nilsson, A. The Structure of the First Coordination
Shell in Liquid Water. Science 2004, 304, 995−999.
(74) Head-Gordon, T.; Johnson, M. E. Tetrahedral Structure or
Chains for Liquid Water. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 7973−
7977.
(75) Pérez, C.; Zaleski, D. P.; Seifert, N. A.; Temelso, B.; Shields, G. C.;
Kisiel, Z.; Pate, B. H. Hydrogen Bond Cooperativity and the Three-
Dimensional Structures of Water Nonamers and Decamers. Angew.
Chem., Int. Ed. 2014, 53, 14368−14372.
(76) Schmidt, D. A.; Miki, K. Structural Correlations in Liquid Water:
A New Interpretation of IR Spectroscopy. J. Phys. Chem. A 2007, 111,
10119−10122.
(77) Maes, G.; Smets, J. Hydrogen Bond Cooperativity. A Quantitative
Study Using Matrix-Isolation m-IR Spectroscopy. J. Phys. Chem. 1993,
97, 1818−1825.
(78) Tse, Y.-C.; Newton, M. D. Theoretical Observations on the
Structural Consequences of Cooperativity in H–O Hydrogen Bonding.
J. Am. Chem. Soc. 1977, 99, 611−613.
(79) Koehler, J. E. H.; Saenger, W.; Lesyng, B. Cooperative Effects in
Extended Hydrogen Bonded Systems Involving O-H Groups. Ab Initio
Studies of the Cyclic S4 Water Tetramer. J. Comput. Chem. 1987, 8,
1090−1098.
(80) Suhai, S. Cooperative effects in hydrogen bonding: Fourth-order
many-body perturbation theory studies of water oligomers and of an
infinite water chain as a model for ice. J. Chem. Phys. 1994, 101, 9766−
9782.
(81) Xantheas, S. S. Cooperativity and hydrogen bonding network in
water clusters. Chem. Phys. 2000, 258, 225−231.
(82) Mó, O.; Yáñez, M.; Elguero, J. Cooperative (nonpairwise) effects
in water trimers: An ab initio molecular orbital study. J. Chem. Phys.
1992, 97, 6628−6638.
(83) Parthasarathi, R.; Subramanian, V.; Sathyamurthy, N. Hydrogen
Bonding in Phenol, Water, and Phenol-Water Clusters. J. Phys. Chem. A
2005, 109, 843−850.
(84) Neela, Y. I.; Mahadevi, A. S.; Sastry, G. N. Hydrogen Bonding in
Water Clusters and Their Ionized Counterparts. J. Phys. Chem. B 2010,
114, 17162−17171.
(85) Ohno, K.; Okimura, M.; Akai, N.; Katsumoto, Y. The effect of
cooperative hydrogen bonding on the OH stretching-band shift for
water clusters studied by matrix-isolation infrared spectroscopy and
density functional theory. Phys. Chem. Chem. Phys. 2005, 7, 3005−3014.
(86) Znamenskiy, V. S.; Green, M. E. Quantum Calculations on
Hydrogen Bonds in Certain Water Clusters Show Cooperative Effects. J.
Chem. Theory Comput. 2007, 3, 103−114.
(87) Ruckenstein, E.; Shulgin, I. L.; Shulgin, L. I. Cooperativity in
Ordinary Ice and Breaking of Hydrogen Bonds. J. Phys. Chem. B 2007,
111, 7114−7121.
(88) Stokely, K.; Mazza, M. G.; Stanley, H. E.; Franzese, G. Effect of
Hydrogen Bond Cooperativity on the Behavior of Water. Proc. Natl.
Acad. Sci. U. S. A. 2010, 107, 1301−1306.
(89) Albrecht, L.; Chowdhury, S.; Boyd, R. J. Hydrogen Bond
Cooperativity in Water Hexamers: Atomic Energy Perspective of Local
Stabilities. J. Phys. Chem. A 2013, 117, 10790−10799.
(90) Sciortino, F.; Fornili, S. L. Hydrogen Bond Cooperativity in
Simulated Water: Time Dependence Analysis of Pair Interactions. J.
Chem. Phys. 1989, 90, 2786−2792.
(91) Ojamaee, L.; Hermansson, K. Ab Initio Study of Cooperativity in
Water Chains: Binding Energies and Anharmonic Frequencies. J. Phys.
Chem. 1994, 98, 4271−4282.
2808
Review
(92) Luck, W. A. P. The Importance of Cooperativity for the Properties
of Liquid Water. J. Mol. Struct. 1998, 448, 131−142.
(93) Keutsch, F. N.; Saykally, R. J. Water Clusters: Untangling the
Mysteries of the Liquid, One Molecule at a Time. Proc. Natl. Acad. Sci. U.
S. A. 2001, 98, 10533−10540.
(94) Agmon, N. Liquid Water: From Symmetry Distortions to
Diffusive Motion. Acc. Chem. Res. 2012, 45, 63−73.
(95) Saha, S.; Sastry, G. N. Quantifying Cooperativity in Water
Clusters: An Attempt towards Obtaining a Generalized Equation. Mol.
Phys. 2015, 113, 3031−3041.
(96) Hannachi, Y.; Silvi, B.; Bouteiller, Y. Ab initio Study of the
Structure, Cooperativity, and Vibrational Properties of the H2O: (HF)2
Hydrogen Bonded Complex. J. Chem. Phys. 1992, 97, 1911−1918.
(97) González, L.; Mó, O.; Yáñez, M. High Level Ab Initio and Density
Functional Theory Studies on Methanol-Water Dimers and Cyclic
Methanol(water)2 Trimer. J. Chem. Phys. 1998, 109, 139−150.
(98) González, L.; Mó, O.; Yáñez, M. Density Functional Theory
Study on Ethanol Dimers and Cyclic Ethanol Trimers. J. Chem. Phys.
1999, 111, 3855−3861.
(99) Nagaraju, M.; Sastry, G. N. Comparative Study on Formamide-
Water Complex. Int. J. Quantum Chem. 2010, 110, 1994−2003.
(100) Nagaraju, M.; Sastry, G. N. Effect of Alkyl Substitution on H-
bond Strength of Substituted Amide-Alcohol Complexes. J. Mol. Model.
2011, 17, 1801−1816.
(101) Masunov, A.; Dannenberg, J. J. Theoretical Study of Urea and
Thiourea. 2. Chains and Ribbons. J. Phys. Chem. B 2000, 104, 806−810.
(102) Kobko, N.; Paraskevas, L.; del Rio, E.; Dannenberg, J. J.
Cooperativity in Amide Hydrogen Bonding Chains: Implications for
Protein-Folding Models. J. Am. Chem. Soc. 2001, 123, 4348−4349.
(103) Dannenberg, J. J. Cooperativity in hydrogen bonded aggregates.
Models for crystals and peptides. J. Mol. Struct. 2002, 615, 219−226.
(104) Kobko, N.; Dannenberg, J. J. Cooperativity in Amide Hydrogen
Bonding Chains. A Comparison between Vibrational Coupling through
Hydrogen Bonds and Covalent Bonds. Implications for Peptide
Vibrational Spectra. J. Phys. Chem. A 2003, 107, 6688−6697.
(105) Kobko, N.; Dannenberg, J. J. Cooperativity in Amide Hydrogen
Bonding Chains. Relation between Energy, Position, and H-Bond Chain
Length in Peptide and Protein Folding Models. J. Phys. Chem. A 2003,
107, 10389−10395.
(106) Asensio, A.; Kobko, N.; Dannenberg, J. J. Cooperative
Hydrogen-Bonding in Adenine-Thymine and Guanine-Cytosine Base
Pairs. Density Functional Theory and Møller-Plesset Molecular Orbital
Study. J. Phys. Chem. A 2003, 107, 6441−6443.
(107) Chen, Y.; Dannenberg, J. J. Cooperative 4-Pyridone H-Bonds
with Extraordinary Stability. A DFT Molecular Orbital Study. J. Am.
Chem. Soc. 2006, 128, 8100−8101.
(108) Mahadevi, A. S.; Neela, Y. I.; Sastry, G. N. A Theoretical Study
on Structural, Spectroscopic and Energetic Properties of Acetamide
Clusters [CH3CONH2] (n = 1−15). Phys. Chem. Chem. Phys. 2011, 13,
15211−15220.
(109) Mahadevi, A. S.; Neela, Y. I.; Sastry, G. N. Hydrogen Bonded
Networks in Formamide [HCONH2]n (n = 1 − 10) clusters: A
Computational Exploration of Preferred Aggregation Patterns. J. Chem.
Sci. 2012, 124, 35−42.
(110) Parra, R. D.; Bulusu, S.; Zeng, X. C. Cooperative Effects in One-
Dimensional Chains of Three-Center Hydrogen Bonding Interactions.
J. Chem. Phys. 2003, 118, 3499−3509.
(111) Parra, R. D.; Bulusu, S.; Zeng, X. C. Cooperative Effects in Two-
Dimensional Ring-Like Networks of Three-Center Hydrogen Bonding
Interactions. J. Chem. Phys. 2005, 122, 184325−8.
(112) Parra, R. D.; Ohlssen, J. Cooperativity in Intramolecular
Bifurcated Hydrogen Bonds: An Ab Initio Study. J. Phys. Chem. A 2008,
112, 3492−3498.
(113) Ludwig, R.; Weinhold, F.; Farrar, T. C. Structure of Liquid N-
Methylacetamide: Temperature Dependence of NMR Chemical Shifts
and Quadrupole Coupling Constants. J. Phys. Chem. A 1997, 101, 8861−
8870.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(114) King, B. F.; Weinhold, F. Structure and Spectroscopy of (HCN)n
Clusters: Cooperative and Electronic Delocalization Effects in C−HN
Hydrogen Bonding. J. Chem. Phys. 1995, 103, 333−347.
(115) Cabaleiro-Lago, E. M.; Ríos, M. A. Ab Initio Study of Interactions
in Hydrazine Clusters of One To Four Molecules: Cooperativity in the
Interaction. J. Phys. Chem. A 1999, 103, 6468−6474.
(116) van Mourik, T.; Dingley, A. J. Characterizing the Cooperativity
in H-Bonded Amino Structures. J. Phys. Chem. A 2007, 111, 11350−
11358.
(117) Jiang, X.; Wang, C. Rapid Prediction of the Hydrogen Bond
Cooperativity in N-methylacetamide Chains. ChemPhysChem 2009, 10,
3330−3336.
(118) Sun, C.; Wang, C. Cooperative Influence of Water Binding to
Peptides by N-H···OH2 and CO···HOH Hydrogen Bonds: Study by
Ab Initio Calculations. Int. J. Quantum Chem. 2012, 112, 2336−2341.
(119) Xia, Q. Y.; Xiao, H. M.; Ju, X. H.; Gong, X. D. DFT Study on
Cooperativity in the Interactions of Hydrazoic Acid Clusters. Int. J.
Quantum Chem. 2003, 94, 279−286.
(120) Kar, T.; Scheiner, S. Comparison of Cooperativity in CH···O
and OH···O Hydrogen Bonds. J. Phys. Chem. A 2004, 108, 9161−9168.
(121) Scheiner, S. Solvation of Hydrogen Bonded Systems: CH···O,
OH···O, and Cooperativity. In Solvation Effects On Molecules And
Biomolecules; Canuto, S., Ed; Springer: The Netherlands, 2008; p 407.
(122) Scheiner, S. Hydrogen Bonding: A Theoretical Perspective; Oxford
University Press: New York, 1997.
(123) Azofra, L. M.; Scheiner, S. Complexation of n SO2 Molecules (n
= 1, 2, 3) with Formaldehyde and Thioformaldehyde. J. Chem. Phys.
2014, 140, 034302−10.
(124) Azofra, L. M.; Scheiner, S. Tetrel, chalcogen, and CH··O
Hydrogen Bonds in Complexes Pairing Carbonyl-Containing Mole-
cules with 1, 2, and 3 molecules of CO2. J. Chem. Phys. 2015, 142,
034307.
(125) Li, Q.; An, X.; Gong, B.; Cheng, J. Cooperativity between OH···
O and CH···O Hydrogen Bonds Involving Dimethyl Sulfoxide-H2O-
H2O Complex. J. Phys. Chem. A 2007, 111, 10166−10169.
(126) Ziółkowski, M.; Grabowski, S. J.; Leszczynski, J. Cooperativity in
Hydrogen-Bonded Interactions: Ab Initio and “Atoms in Molecules”
Analyses. J. Phys. Chem. A 2006, 110, 6514−6521.
(127) Xu, W.; Li, X.; Tan, H.; Chen, G. Theoretical Study on Stabilities
of Multiple Hydrogen Bonded Dimers. Phys. Chem. Chem. Phys. 2006, 8,
4427−4433.
(128) Li, Q.; An, X.; Luan, F.; Li, W.; Gong, B.; Cheng, J.; Sun, J. The
Effect of Methyl Group on the Cooperativity between Three Types of
Hydrogen Bond: O-H···O, C-H···O, and O-H···π. Int. J. Quantum Chem.
2008, 108, 558−566.
(129) Esrafili, M. D.; Beheshtian, J.; Hadipour, N. L. Computational
Study on the Characteristics of the Interaction in Linear Urea Clusters.
Int. J. Quantum Chem. 2011, 111, 3184−3195.
(130) Khedkar, J. K.; Deshmukh, M. M.; Gadre, S. R.; Gejji, S. P.
Hydrogen Bond Energies and Cooperativity in Substituted Calix[n]-
arenes (n = 4, 5). J. Phys. Chem. A 2012, 116, 3739−3744.
(131) Mahadevi, A. S.; Sastry, G. N. Modulation of Hydrogen Bonding
upon Ion Binding: Insights into Cooperativity. Int. J. Quantum Chem.
2014, 114, 145−153.
(132) Zabardasti, A.; Kakanejadi, A.; Moosavi, S.; Bigleri, Z.;
Solimannejad, M. Anticooperativity in Dihydrogen Bonded Clusters
of Ammonia and BeH42‑. J. Mol. Struct.: THEOCHEM 2010, 945, 97−
100.
(133) Zabardasti, A.; Kakanejadi, A.; Ghenaatian, F.; Bigleri, Z. A
Theoretical Study of Cooperative and Anticooperative Effects on
Hydrogen-Bonded Clusters of Water and the Cyanuric Acid. Mol. Simul.
2010, 36, 960−968.
(134) Albrecht, L.; Boyd, R. J. Atomic Energy Analysis of
Cooperativity, Anticooperativity, and Noncooperativity in Small
Clusters of Methanol, Water, and Formaldehyde. Comput. Theor.
Chem. 2015, 1053, 328−336.
(135) Kleeberg, H.; Klein, D.; Luck, W. A. P. Quantitative Infrared
Spectroscopic Investigations of Hydrogen-Bond Cooperativity. J. Phys.
Chem. 1987, 91, 3200−3203.
2809
Review
(136) Guo, H.; Karplus, M. Ab Initio Studies of Hydrogen Bonding of
N-Methylacetamide: Structure, Cooperativity, and Internal Rotational
Barriers. J. Phys. Chem. 1992, 96, 7273−7287.
(137) Missopolinou, D.; Panayiotou, C. Hydrogen Bonding
Cooperativity and Competing Inter- and Intramolecular Associations:
A Unified Approach. J. Phys. Chem. A 1998, 102, 3574−3581.
(138) Dkhissi, A.; Ramaekers, R.; Houben, L.; Adamowicz, L.; Maes,
G. DFT/B3-LYP study of the hydrogen-bonding cooperativity:
application to (2-pyridone)2, 2-pyridone-H2O, 2-pyridone-CH3OH
and 2-pyridone-CH3OCH3. Chem. Phys. Lett. 2000, 331, 553−560.
(139) Sum, A. K.; Sandler, S. I. Ab Initio Calculations of Cooperativity
Effects on Clusters of Methanol, Ethanol, 1-Propanol, and Meth-
anethiol. J. Phys. Chem. A 2000, 104, 1121−1129.
(140) Zabardasti, A.; Amani, S.; Solimannejad, M.; Salehnassaj, M.
Theoretical Study and Atoms in Molecule Analysis of Hydrogen
Bonded Clusters of Ammonia and Isocyanic Acid. Struct. Chem. 2009,
20, 1087−1092.
(141) Mandal, A.; Prakash, M.; Kumar, R. M.; Parthasarathi, R.;
Subramanian, V. Ab Initio and DFT Studies on Methanol-Water
Clusters. J. Phys. Chem. A 2010, 114, 2250−2258.
(142) Li, Q.; Jiang, L.; Wang, X.; Li, W.; Cheng, J.; Sun, J. Ab Initio
Study of the Structure, Cooperativity, and Vibrational Properties in the
Mixed Hydrogen-Bonded Trimers of Hydrogen Isocyanide and Water.
Int. J. Quantum Chem. 2011, 111, 1072−1080.
(143) Albrecht, L.; Boyd, R. J. Visualizing Internal Stabilization in
Weakly Bound Systems Using Atomic Energies: Hydrogen Bonding in
Small Water Clusters. J. Phys. Chem. A 2012, 116, 3946−3951.
(144) Schiros, T.; Ogasawara, H.; Näslund, L.-Å.; Andersson, K. J.;
Ren, J.; Meng, S.; Karlberg, G. S.; Odelius, M.; Nilsson, A.; Pettersson, L.
G. M. Cooperativity in Surface Bonding and Hydrogen Bonding of
Water and Hydroxyl at Metal Surfaces. J. Phys. Chem. C 2010, 114,
10240−10248.
(145) Rincón, L.; Almeida, R.; Aldea, D. G. Many-Body Energy
Decomposition Analysis of Cooperativity in Hydrogen Fluoride
Clusters. Int. J. Quantum Chem. 2005, 102, 443−453.
(146) Li, Q.; Liu, Z.; Cheng, J.; Li, W.; Gong, B.; Sun, J. Theoretical
Study on the Cooperativity of Hydrogen Bonds in (HNC)2···HF
Complexes. J. Mol. Struct.: THEOCHEM 2009, 896, 112−115.
(147) Qi, H. W.; Leverentz, H. R.; Truhlar, D. G. Water 16-mers and
Hexamers: Assessment of the Three-Body and Electrostatically
Embedded Many-Body Approximations of the Correlation Energy or
the Nonlocal Energy As Ways to Include Cooperative Effects. J. Phys.
Chem. A 2013, 117, 4486−4499.
(148) Shibl, M. F.; Pietrzak, M.; Limbach, H.; Kühn, O. Geometric H/
D Isotope Effects and Cooperativity of the Hydrogen Bonds in
Porphycene. ChemPhysChem 2007, 8, 315−321.
(149) Li, Q.; An, X.; Luan, F.; Li, W.; Gong, B.; Cheng, J.; Sun, J.
Cooperativity between Two Types of Hydrogen Bond in H3C−HCN−
HCN and H3C−HNC−HNC Complexes. J. Chem. Phys. 2008, 128,
154102−6.
(150) Li, Q.; Hu, T.; An, X.; Gong, B.; Cheng, J. Cooperativity between
the Dihydrogen Bond and the N···HC Hydrogen Bond in LiH−
(HCN)n Complexes. ChemPhysChem 2008, 9, 1942−1946.
(151) Alkorta, I.; Blanco, F.; Elguero, J. Dihydrogen Bond
Cooperativity in Aza-borane Derivatives. J. Phys. Chem. A 2010, 114,
8457−8462.
(152) Latajka, Z.; Scheiner, S. Structure, Energetics and Vibrational
Spectra of Dimers, Trimers, and Tetramers of HX(X = C1, Br, I). Chem.
Phys. 1997, 216, 37−52.
(153) Rossetti, G.; Magistrato, A.; Pastore, A.; Carloni, P. Hydrogen
Bonding Cooperativity in polyQ β-Sheets from First Principle
Calculations. J. Chem. Theory Comput. 2010, 6, 1777−1782.
(154) Gung, B. W.; Zhu, Z.; Zou, D.; Everingham, B.; Oyeamalu, A.;
Crist, R. M.; Baudlier, J. Requirement for Hydrogen-Bonding
Cooperativity in Small Polyamides: A Combined VT-NMR and VT-
IR Investigation. J. Org. Chem. 1998, 63, 5750−5761.
(155) Knott, M.; Chan, H. S. Exploring the Effects of Hydrogen
Bonding and Hydrophobic Interactions on the Foldability and
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
Cooperativity of Helical Proteins Using a Simplified Atomic Model.
Chem. Phys. 2004, 307, 187−199.
(156) Wieczorek, R.; Dannenberg, J. J. Hydrogen Bond Cooperativity,
Vibrational Coupling, and Dependence of Helix Stability on Changes in
Amino Acid Sequence in Small 310-Helical Peptides. A Density
Functional Theory Study. J. Am. Chem. Soc. 2003, 125, 14065−14071.
(157) Wieczorek, R.; Dannenberg, J. J. H-Bonding Cooperativity and
Energetics of α-Helix Formation of Five 17-Amino Acid Peptides. J. Am.
Chem. Soc. 2003, 125, 8124−8129.
(158) Wieczorek, R.; Dannenberg, J. J. Comparison of Fully Optimized
α- and 310-Helices with Extended β-Strands. An ONIOM Density
Functional Theory Study. J. Am. Chem. Soc. 2004, 126, 14198−14205.
(159) Salvador, P.; Kobko, N.; Wieczorek, R.; Dannenberg, J. J.
Calculation of trans-Hydrogen-Bond 13C-15N Three-Bond and Other
Scalar J-Couplings in Cooperative Peptide Models. A Density
Functional Theory Study. J. Am. Chem. Soc. 2004, 126, 14190−14197.
(160) Sheridan, R. P.; Lee, R. H.; Peters, N.; Allen, L. C. Hydrogen-
Bond Cooperativity in Protein Secondary Structure. Biopolymers 1979,
18, 2451−2458.
(161) Van Duijnen, P. T.; Thole, B. T. Cooperative Effects in α-
Helices: An Ab Initio Molecular-Orbital Study. Biopolymers 1982, 21,
1749−1761.
(162) Kennedy, R. J.; Tsang, K.; Kemp, D. S. Consistent Helicities
from CD and Template t/c Data for N-Templated Polyalanines:
Progress toward Resolution of the Alanine Helicity Problem. J. Am.
Chem. Soc. 2002, 124, 934−944.
(163) Wu, Y.; Zhao, Y. A Theoretical Study on the Origin of
Cooperativity in the Formation of 310- and α-Helices. J. Am. Chem. Soc.
2001, 123, 5313−5319.
(164) Zhao, Y.; Wu, Y. A Theoretical Study of β-Sheet Models: Is the
Formation of Hydrogen-Bond Networks Cooperative? J. Am. Chem. Soc.
2002, 124, 1570−1571.
(165) Morozov, A. V.; Tsemekhman, K.; Baker, D. Electron Density
Redistribution Accounts for Half the Cooperativity of α Helix
Formation. J. Phys. Chem. B 2006, 110, 4503−4505.
(166) Tsemekhman, K.; Goldschmidt, L.; Eisenberg, D.; Baker, D.
Cooperative Hydrogen Bonding in Amyloid Formation. Protein Sci.
2007, 16, 761−764.
(167) Wieczorek, R.; Dannenberg, J. J. Amide I Vibrational
Frequencies of α-Helical Peptides Based upon ONIOM and Density
Functional Theory (DFT) Studies. J. Phys. Chem. B 2008, 112, 1320−
1328.
(168) Plumley, J. A.; Dannenberg, J. J. The Importance of Hydrogen
Bonding between the Glutamine Side Chains to the Formation of
Amyloid VQIVYK Parallel β-Sheets: An ONIOM DFT/AM1 Study. J.
Am. Chem. Soc. 2010, 132, 1758−1759.
(169) Ireta, J.; Neugebauer, J.; Scheffler, M.; Rojo, A.; Galván, M.
Density Functional Theory Study of the Cooperativity of Hydrogen
Bonds in Finite and Infinite α-Helices. J. Phys. Chem. B 2003, 107,
1432−1437.
(170) Parker, L. L.; Houk, A. R.; Jensen, J. H. Cooperative Hydrogen
Bonding Effects Are Key Determinants of Backbone Amide Proton
Chemical Shifts in Proteins. J. Am. Chem. Soc. 2006, 128, 9863−9872.
(171) Albeck, S.; Unger, R.; Schreiber, G. Evaluation of Direct and
Cooperative Contributions Towards the Strength of Buried Hydrogen
Bonds and Salt Bridges. J. Mol. Biol. 2000, 298, 503−520.
(172) Kung, V. M.; Cornilescu, G.; Gellman, S. H. Impact of Strand
Number on Parallel β-Sheet Stability. Angew. Chem., Int. Ed. 2015, 54,
14336.
(173) Nochebuena, J.; Ireta, J. On Cooperative Effects and
Aggregation of GNNQQNY and NNQQNY Peptides. J. Chem. Phys.
2015, 143, 135103.
(174) Dashnau, J. L.; Sharp, K. A.; Vanderkooi, J. M. Carbohydrate
Intramolecular Hydrogen Bonding Cooperativity and Its Effect on
Water Structure. J. Phys. Chem. B 2005, 109, 24152−24159.
(175) Deshmukh, M. M.; Bartolotti, L. J.; Gadre, S. R. Intramolecular
Hydrogen Bonding and Cooperative Interactions in Carbohydrates via
the Molecular Tailoring Approach. J. Phys. Chem. A 2008, 112, 312−
321.
2810
Review
(176) Vicente, V.; Martin, J.; Jiménez-Barbero, J.; Chiara, J. L.; Vicent,
C. Hydrogen-Bonding Cooperativity: Using an Intramolecular Hydro-
gen Bond To Design a Carbohydrate Derivative with a Cooperative
Hydrogen-Bond Donor Centre. Chem.−Eur. J. 2004, 10, 4240−4251.
(177) Gilli, G.; Bellucci, F.; Ferretti, V.; Bertolasi, V. Evidence for
Resonance-Assisted Hydrogen Bonding from Crystal-Structure Corre-
lations on the Enol Form of the β-Diketone Fragment. J. Am. Chem. Soc.
1989, 111, 1023−1028.
(178) Bertolasi, V.; Cilli, P.; Ferretti, V.; Gilli, G. Evidence for
Resonance-Assisted Hydrogen Bonding. 2.1 Intercorrelation between
Crystal Structure and Spectroscopic Parameters in Eight Intra-
molecularly Hydrogen Bonded 1,3-Diaryl-1,3-propanedione Enols. J.
Am. Chem. Soc. 1991, 113, 4917−4925.
(179) Bertolasi, V.; Pretto, L.; Gilli, G.; Gilli, P. π-Bond Cooperativity
and Anticooperativity Effects in Resonance-Assisted Hydrogen Bonds
(RAHBs). Acta Crystallogr., Sect. B: Struct. Sci. 2006, 62, 850−863.
(180) Mignon, P.; Loverix, S.; Steyaert, J.; Geerlings, P. Influence of the
π−π Interaction on the Hydrogen Bonding Capacity of Stacked DNA/
RNA Bases. Nucleic Acids Res. 2005, 33, 1779−1789.
(181) Vijay, D.; Zipse, H.; Sastry, G. N. On the Cooperativity of
Cation-π and Hydrogen Bonding Interactions. J. Phys. Chem. B 2008,
112, 8863−8867.
(182) Kruszynski, R.; Trzesowska-Kruszynska, A. Halogen, Hydrogen
and Electrostatic Interactions in 2-amino-5-chloro-1,3-benzoxazol-3-
ium nitrate and 2-amino-5-chloro-1,3-benzoxazol-3-ium perchlorate.
Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 2010, 66, o449−o454.
(183) Rieth, S.; Li, Z.; Hinkle, C. E.; Guzman, C. X.; Lee, J. J.; Nehme,
S. I.; Braunschweig, A. B. Superstructures of Diketopyrrolopyrrole
Donors and Perylenediimide Acceptors Formed by Hydrogen-Bonding
and π···π Stacking. J. Phys. Chem. C 2013, 117, 11347−11356.
(184) León, I.; Millán, J.; Cocinero, E. J.; Lesarri, A.; Fernández, J. A.
Shaping Micelles: The Interplay between Hydrogen Bonds and
Dispersive Interactions. Angew. Chem., Int. Ed. 2013, 52, 7772−7775.
(185) Seifert, N. A.; Steber, A. L.; Neill, J. L.; Pérez, C.; Zaleski, D. P.;
Pate, B. H.; Lesarri, A. The Interplay of Hydrogen Bonding and
Dispersion in Phenol Dimer and Trimer: Structures from Broadband
Rotational Spectroscopy. Phys. Chem. Chem. Phys. 2013, 15, 11468−
11477.
(186) Guo, J.; Shi, W.; Ren, F.; Cao, D.; Zhang, Y. A B3LYP and
MP2(full) Theoretical Investigation into the Cooperativity Effect
between Dihydrogen-Bonding and H−M•••π (M = Li, Na, K)
Interactions among HF, MH with the π-Electron Donor C2H2, C2H4 or
C6H6. J. Mol. Model. 2013, 19, 3153−3163.
(187) Alkorta, I.; Elguero, J.; Solimannejad, M.; Grabowski, S. J.
Dihydrogen Bonding vs Metal-σ Interaction in Complexes between H2
and Metal Hydride. J. Phys. Chem. A 2011, 115, 201−210.
(188) Kovács, A.; Varga, Z. Halogen Acceptors in Hydrogen Bonding.
Coord. Chem. Rev. 2006, 250, 710−727.
(189) Grabowski, S. J. Cooperativity of Hydrogen and Halogen Bond
Interactions. Theor. Chem. Acc. 2013, 132, 1347.
(190) Jing, B.; Li, Q.; Li, R.; Gong, B.; Liu, Z.; Li, W.; Cheng, J.; Sun, J.
Competition and Cooperativity between Hydrogen Bond and Halogen
Bond in HNC···(HOBr)n and (HNC)n···HOBr (n = 1 and 2) Systems.
Comput. Theor. Chem. 2011, 963, 417−421.
(191) Li, Q.; Lin, Q.; Li, W.; Cheng, J.; Gong, B.; Sun, J. Cooperativity
between the Halogen Bond and the Hydrogen Bond in H3N···XY···HF
Complexes (X, Y = F, Cl, Br). ChemPhysChem 2008, 9, 2265−2269.
(192) Li, Q.; Ma, S.; Liu, X.; Li, W.; Cheng, J. Cooperative and
Substitution Effects in Enhancing Strengths of Halogen Bonds in
FClCNX Complexes. J. Chem. Phys. 2012, 137, 084314−8.
(193) Wu, W.; Zeng, Y.; Li, X.; Zhang, X.; Zheng, S.; Meng, L. Interplay
between Halogen Bonds and Hydrogen Bonds in OH/SH···HOX···HY
(X = Cl, Br; Y = F, Cl, Br) Complexes. J. Mol. Model. 2013, 19, 1069−
1077.
(194) McDowell, S. A. C.; Yarde, H. K. Cooperative effects of
Hydrogen, Lithium and Halogen Bonding on F−H/Li···OH 2
Complexes. Phys. Chem. Chem. Phys. 2012, 14, 6883−6888.
(195) Domagała, M.; Palusiak, M. The Influence of Substituent Effect
on Noncovalent Interactions in Ternary Complexes Stabilized by
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
Hydrogen-Bonding and Halogen-Bonding. Comput. Theor. Chem. 2014,
1027, 173−178.
(196) Li, Q.; Hu, T.; An, X.; Li, W.; Cheng, J.; Gong, B.; Sun, J.
Theoretical Study of the Interplay between Lithium Bond and
Hydrogen Bond in Complexes Involved with HLi and HCN.
ChemPhysChem 2009, 10, 3310−3315.
(197) Albrecht, L.; Boyd, R. J.; Mó, O.; Yáñez, M. Cooperativity
between Hydrogen Bonds and Beryllium Bonds in (H2O)nBeX2 (n = 1−
3, X = H, F) Complexes. A New Perspective. Phys. Chem. Chem. Phys.
2012, 14, 14540−14547.
(198) Alberto, M. E.; Mazzone, G.; Russo, N.; Sicilia, E. The Mutual
Influence of Noncovalent Interactions in π-Electron Deficient Cavities:
The Case of Anion Recognition by Tetraoxacalix[2]arene[2]triazine.
Chem. Commun. 2010, 46, 5894−5896.
(199) Natale, D.; Mareque-Rivas, J. C. The Combination of Transition
Metal Ions and Hydrogen Bonding Interactions. Chem. Commun. 2008,
425−437.
(200) Seifert, N. A.; Zaleski, D. P.; Pérez, C.; Neill, J. L.; Pate, B. H.;
Vallejo-López, M.; Lesarri, A.; Cocinero, E. J.; Castaño, F.; Kleiner, I.
Probing the C-H···π Weak Hydrogen Bond in Anesthetic Binding: The
Sevoflurane−Benzene Cluster. Angew. Chem., Int. Ed. 2014, 53, 3210−
3213.
(201) Kobayashi, Y.; Saigo, K. Periodic Ab Initio Approach for the
Cooperative Effect of CH/π Interaction in Crystals: Relative Energy of
CH/π and Hydrogen-Bonding Interactions. J. Am. Chem. Soc. 2005, 127,
15054−15060.
(202) Li, Q.; Li, H.; Li, R.; Jing, B.; Liu, Z.; Li, W.; Luan, F.; Cheng, J.;
Gong, B.; Sun, J. Influence of Hybridization and Cooperativity on the
Properties of Au-Bonding Interaction: Comparison with Hydrogen
Bonds. J. Phys. Chem. A 2011, 115, 2853−2858.
(203) Grabowski, S. J.; Leszczynski, J. The Enhancement of X−H···π
Hydrogen Bond by Cooperativity Effects − Ab initio and QTAIM
calculations. Chem. Phys. 2009, 355, 169−176.
(204) Mo, Y. Can QTAIM Topological Parameters Be a Measure of
Hydrogen Bonding Strength? J. Phys. Chem. A 2012, 116, 5240−5246.
(205) Gholipour, A. R.; Saydi, H.; Neiband, M. S.; Neyband, R. S.
Simultaneous Interactions of Pyridine with Substituted Benzene Ring
and H−F in X-ben⊥pyr···H−F Complexes: A Cooperative Study. Struct.
Chem. 2012, 23, 367−373.
(206) Solimannejad, M.; Rezaei, Z.; Esrafili, M. D. Competition and
Interplay between the Lithium Bonding and Hydrogen Bonding: R3C···
HY···LiY and R3C···LiY···HY Triads as a Working Model (R = H, CH3;
Y = CN, NC). J. Mol. Model. 2013, 19, 5031−5035.
(207) Solimannejad, M.; Malekani, M.; Alkorta, I. Cooperativity
between the Hydrogen Bonding and Halogen Bonding in F3CX···
NCH(CNH)···NCH(CNH) complexes (X = Cl, Br). Mol. Phys. 2011,
109, 1641−1648.
(208) Tian, Q.; Wang, Y.; Shi, W.; Song, S.; Tang, H. A Theoretical
Investigation into the Cooperativity Effect between the H···O and H···
F−Interactions and Electrostatic Potential upon 1:2 (F − :N-
(Hydroxymethyl)acetamide) Ternary-System Formation. J. Mol.
Model. 2013, 19, 5171−5185.
(209) Kříž, J.; Dautzenberg, H. Cooperative Interactions of Unlike
Macromolecules 2: NMR and Theoretical Study of Electrostatic Binding
of Sodium Poly(styrenesulfonate)s to Copolymers with Variably
Distributed Cationic Groups. J. Phys. Chem. A 2001, 105, 3846−3854.
(210) Kříž, J.; Dybal, J. Cooperative Hydrogen Bonds of Macro-
molecules. 3. A Model Study of the Proximity Effect. J. Phys. Chem. B
2007, 111, 6118−6126.
(211) Remya, K.; Suresh, C. H. Cooperativity and Cluster Growth
Patterns in Acetonitrile: A DFT Study. J. Comput. Chem. 2014, 35, 910−
922.
(212) Mohan, N.; Suresh, C. H. Accurate Binding Energies of
Hydrogen, Halogen, and Dihydrogen Bonded Complexes and Cation
Enhanced Binding Strengths. Int. J. Quantum Chem. 2014, 114, 885−
894.
(213) Zhuo, H.; Li, Q.; Li, W.; Cheng, J. Non-additivity between
Substitution and Cooperative Effects in Enhancing Hydrogen Bonds. J.
Chem. Phys. 2014, 141, 244305.
2811
Review
(214) Anand, M.; Fernandez, I.; Schaefer, H. F., III; Wu, J. I. Hydrogen
Bond−Aromaticity Cooperativity in Self-Assembling 4-Pyridone
Chains. J. Comput. Chem. 2016, 37, 59.
(215) Axilrod, B. M.; Teller, E. Interaction of the van der Waals Type
between Three Atoms. J. Chem. Phys. 1943, 11, 299−300.
(216) Muto, Y. Force between Nonpolar Molecules. Proc. Phys.-Math
Soc. Jpn. 1943, 17, 629−631.
(217) Bates, D. M.; Smith, J. R.; Janowski, T.; Tschumper, G. S.
Development of a 3-Body: Many-Body Integrated Fragmentation
Method for Weakly Bound Clusters and Application to Water Clusters
(H2O)n=3−10, 16, 17. J. Chem. Phys. 2011, 135, 044123−8.
(218) Góra, U.; Podeszwa, R.; Cencek, W.; Szalewicz, K. Interaction
Energies of Large Clusters from Many-Body Expansion. J. Chem. Phys.
2011, 135, 224102.
(219) Shimizu, S.; Chan, H. S. AntiCooperativity and Cooperativity in
Hydrophobic Interactions: Three-Body Free Energy Landscapes and
Comparison with Implicit-Solvent Potential Functions for Proteins.
Proteins: Struct., Funct., Genet. 2002, 48, 15−30.
(220) Matsumoto, M. Four-Body Cooperativity in Hydrophonic
Association of Methane. J. Phys. Chem. Lett. 2010, 1, 1552−1556.
(221) von Lilienfeld, O. A.; Tkatchenko, A. Two- and Three-Body
Interatomic Dispersion Energy Contributions to Binding in Molecules
and Solids. J. Chem. Phys. 2010, 132, 234109−11.
(222) Wang, L.; Friesner, R. A.; Berne, B. J. Hydrophobic Interactions
in Model Enclosures from Small to Large Length Scales: Nonadditivity
in Explicit and Implicit Solvent Models. Faraday Discuss. 2010, 146,
247−262.
(223) Farina, C.; Santos, F. C.; Tort, A. C. A Simple Way of
Understanding the Nonadditivity of van der Waals Dispersion Forces.
Am. J. Phys. 1999, 67, 344−349.
(224) Sponer, J.; Gabb, H. A.; Leszczynski, J.; Hobza, P. Base-Base and
Deoxyribose-Base Stacking Interactions in B-DNA and Z-DNA: A
Quantum-Chemical Study. Biophys. J. 1997, 73, 76−87.
(225) Valiron, P.; Mayer, I. Hierarchy of Counterpoise Corrections for
N-body Clusters: Generalization of the Boys-Bernardi Scheme. Chem.
Phys. Lett. 1997, 275, 46−55.
(226) Tkatchenko, A.; von Lilienfeld, O. A. Popular Kohn-Sham
Density Functionals Strongly Overestimate Many-Body Interactions in
van der Waals Systems. Phys. Rev. B: Condens. Matter Mater. Phys. 2008,
78, 045116−6.
(227) Chmela, J.; Harding, M. E.; Matioszek, D.; Anson, C. E.; Breher,
F.; Klopper, W. Differential Many-Body Cooperativity in Electronic
Spectra of Oligonuclear Transition-Metal Complexes. ChemPhysChem
2015, DOI: 10.1002/cphc.201500626.
(228) Schreiber, G.; Fersht, A. R. Energetics of Protein-Protein
Interactions: Analysis of the Barnase-Barstar Interface by Single
Mutations and Double Mutant Cycles. J. Mol. Biol. 1995, 248, 478−486.
(229) Searle, M. S.; Griffiths-Jones, S. R.; Skinner-Smith, H. Energetics
of Weak Interactions in a β-hairpin Peptide: Electrostatic and
Hydrophobic Contributions to Stability from Lysine Salt Bridges. J.
Am. Chem. Soc. 1999, 121, 11615−11620.
(230) Ullmann, R. T.; Ullmann, G. M. Coupling of Protonation,
Reduction, and Conformational Change in Azurin from Pseudomonas
aeruginosa Investigated with Free Energy Measures of Cooperativity. J.
Phys. Chem. B 2011, 115, 10346−10359.
(231) Hunter, C. A.; Jones, P. S.; Tiger, P.; Tomas, S. Chemical Triple-
Mutant Boxes for Quantifying Cooperativity in Intermolecular
Interactions. Chem. - Eur. J. 2002, 8, 5435−5446.
(232) Hunter, C. A.; Tomas, S. Cooperativity, Partially Bound States,
and Enthalpy-Entropy Compensation. Chem. Biol. 2003, 10, 1023−
1032.
(233) Camara-Campos, A.; Musumeci, D.; Hunter, C. A.; Turega, S.
Chemical Double Mutant Cycles for the Quantification of Cooperativity
in H-Bonded Complexes. J. Am. Chem. Soc. 2009, 131, 18518−18524.
(234) Hunter, C. A.; Misuraca, M. C.; Turega, S. M. Solvent Effects on
Chelate Cooperativity. Chem. Sci. 2012, 3, 589−601.
(235) Acerenza, L.; Mizraji, E. Cooperativity: A Unified View. Biochim.
Biophys. Acta, Protein Struct. Mol. Enzymol. 1997, 1339, 155−166.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(236) Bloom, C. R.; Kaarsholm, N. C.; Ha, J.; Dunn, M. F. Half-Site
Reactivity, Negative Cooperativity, and Positive Cooperativity:
Quantitative Considerations of a Plausible Model. Biochemistry 1997,
36, 12759−12765.
(237) Andersen, P. S.; Schuck, P.; Sundberg, E. J.; Geisler, C.;
Karjalainen, K.; Mariuzza, R. A. Quantifying the Energetics of
Cooperativity in a Ternary Protein Complex. Biochemistry 2002, 41,
5177−5184.
(238) Ng, C. K. L.; Li, N. X.; Chee, S.; Prabhakar, S.; Kolatkar, P. R.;
Jauch, R. Deciphering the Sox-Oct Partner Code by Quantitative
Cooperativity Measurements. Nucleic Acids Res. 2012, 40, 4933−4941.
(239) Varfolomeev, M. A.; Klimovitskii, A. E.; Abaidullina, D. I.;
Madzhidov, T. I.; Solomonov, B. N. Additive” Cooperativity of
Hydrogen Bonds in Complexes of Catechol with Proton Acceptors in
the Gas Phase: FTIR Spectroscopy and Quantum Chemical
Calculations. Spectrochim. Acta, Part A 2012, 91, 75−82.
(240) Roubeau, O.; Castro, M.; Burriel, R.; Haasnoot, J. G.; Reedijk, J.
Calorimetric Investigation of Triazole-Bridged Fe(II) Spin-Crossover
One-Dimensional Materials: Measuring the Cooperativity. J. Phys.
Chem. B 2011, 115, 3003−3012.
(241) Garcés, J. L.; Acerenza, L.; Mizraji, E.; Mas, F. A Hierarchical
Approach to Cooperativity in Macromolecular and Self-Assembling
Binding Systems. J. Biol. Phys. 2008, 34, 213−235.
(242) Douglas, J. F.; Dudowicz, J.; Freed, K. F. Lattice Model of
Equilibrium Polymerization. VII. Understanding the Role of “Cooper-
ativity” in Self-Assembly. J. Chem. Phys. 2008, 128, 224901−17.
(243) Hamacek, J.; Borkovec, M.; Piguet, C. A Simple Thermodynamic
Model for Quantitatively Addressing Cooperativity in Multicomponent
Self-Assembly ProcessesPart 1: Theoretical Concepts and Applica-
tion to Monometallic Coordination Complexes and Bimetallic Helicates
Possessing Identical Binding Sites. Chem. - Eur. J. 2005, 11, 5217−5226.
(244) Douglass, E. F., Jr.; Miller, C. J.; Sparer, G.; Shapiro, H.; Spiegel,
D. A. A Comprehensive Mathematical Model for Three-Body Binding
Equilibria. J. Am. Chem. Soc. 2013, 135, 6092−6099.
(245) Wang, R.; Nganso, D. S.; Kaabouchi, E. A.; Wang, Q. A.
Investigation of an Energy Nonadditivity for Nonextensive Systems.
Chin. Sci. Bull. 2011, 56, 3661−3665.
(246) Kumar, R. M.; Vijay, D.; Sastry, G. N.; Subramanian, V.
Intermolecular Interactions through Energy Decomposition A Chem-
ists’ Perspective. In Concepts and Methods in Modern Theoretical
Chemistry; Ghosh, S. K., Chattaraj, P. K., Eds.; CRC Press, 2013; p 313.
(247) White, J. C.; Davidson, E. R. An Analysis of the Hydrogen Bond
in Ice. J. Chem. Phys. 1990, 93, 8029−8035.
(248) Vijay, D.; Sastry, G. N. The Cooperativity of Cation−π and π−π
Interactions. Chem. Phys. Lett. 2010, 485, 235−242.
(249) Li, Q.; Zhuo, H.; Yang, X.; Cheng, J.; Li, W.; Loffredo, R. E.
Cooperative and Diminutive Effects of Pnicogen Bonds and Cation−π
Interactions. ChemPhysChem 2014, 15, 500−506.
(250) Carrazana-García, J. A.; Rodríguez-Otero, J.; Cabaleiro-Lago, E.
M. A Computational Study of Anion-Modulated Cation−π Interactions.
J. Phys. Chem. B 2012, 116, 5860−5871.
(251) Antony, J.; Brüske, B.; Grimme, S. Cooperativity in Noncovalent
Interactions of Biologically Relevant Molecules. Phys. Chem. Chem. Phys.
2009, 11, 8440−8447.
(252) Mandal, T. K.; Samanta, S.; Chakraborty, S.; Datta, A. An
Interplay of Cooperativity between Cation···π, Anion···π and CH···
Anion Interactions. ChemPhysChem 2013, 14, 1149−1154.
(253) Liu, X.; Li, Q.; Cheng, J.; Li, W. Influence of Cooperativity on the
Frequency Shift of the Ar−H Stretch Vibration in HArF Complexes.
Mol. Phys. 2013, 111, 497−504.
(254) Li, Q.; Zhu, H.; An, X.; Gong, B.; Cheng, J. Nonadditivity of
Methyl Group in Single-Electron Hydrogen Bond of Methyl Radical-
Water Complex. Int. J. Quantum Chem. 2009, 109, 605−611.
(255) Vijay, D.; Sakurai, H.; Subramanian, V.; Sastry, G. N. Where to
Bind in Buckybowls? The Dilemma of a Metal Ion. Phys. Chem. Chem.
Phys. 2012, 14, 3057−3065.
(256) Premkumar, J. R.; Vijay, D.; Sastry, G. N. The Significance of the
Alkene Size and the Nature of the Metal Ion in Metal−Alkene
Complexes: A Theoretical Study. Dalton Trans. 2012, 41, 4965−4975.
2812
Review
(257) Mahadevi, A. S.; Sastry, G. N. A Theoretical Study on Interaction
of Cyclopentadienyl Ligand with Alkali and Alkaline Earth Metals. J.
Phys. Chem. B 2011, 115, 703−710.
(258) Vijay, D.; Sastry, G. N. Exploring the Size Dependence of Cyclic
and Acyclic π-Systems on Cation−π Binding. Phys. Chem. Chem. Phys.
2008, 10, 582−590.
(259) Vijay, D.; Sastry, G. N. A Computational Study on π and σ
Modes of Metal Ion Binding to Heteroaromatics (CH)5‑mXm and
(CH)6‑mXm (X = N and P): Contrasting Preferences between Nitrogen
and Phosphorous-Substituted Rings. J. Phys. Chem. A 2006, 110,
10148−10154.
(260) Sharma, B.; Umadevi, D.; Sastry, G. N. Contrasting Preferences
of N and P Substituted Heteroaromatics Towards Metal Binding:
Probing the Regioselectivity of Li+ and Mg2+ binding to (CH)6‑m‑nNmPn.
Phys. Chem. Chem. Phys. 2012, 14, 13922−13932.
(261) Priyakumar, U. D.; Punnagai, M.; Krishna Mohan, G. P.; Sastry,
G. N. A Computational Study of Cation−π Interactions in Polycyclic
Systems: Exploring the Dependence on the Curvature and Electronic
Factors. Tetrahedron 2004, 60, 3037−3043.
(262) Priyakumar, U. D.; Sastry, G. N. Cation-π Interactions of Curved
Polycyclic Systems: M+ (M = Li and Na) Ion Complexation with
Buckybowls. Tetrahedron Lett. 2003, 44, 6043−6046.
(263) Priyakumar, U. D.; Sastry, G. N. Structures, Energetics, Relative
Stabilities, and Out-of-Plane Distortivities of Skeletally Disubstituted
Benzenes, (CH)4X2 (X = N, P, C−, Si−, O+, and S+): An Ab Initio and
DFT Study. J. Am. Chem. Soc. 2000, 122, 11173−11181.
(264) Priyakumar, U. D.; Sastry, G. N. Heterobuckybowls: A
Theoretical Study on the Structure, Bowl-to-Bowl Inversion Barrier,
Bond Length Alternation, Structure-Inversion Barrier Relationship,
Stability, and Synthetic Feasibility. J. Org. Chem. 2001, 66, 6523−6530.
(265) Priyakumar, U. D.; Sastry, G. N. First Ab Initio and Density
Functional Study on the Structure, Bowl-to-Bowl Inversion Barrier, and
Vibrational Spectra of the Elusive C3v-Symmetric Buckybowl:
Sumanene, C21H12. J. Phys. Chem. A 2001, 105, 4488−4494.
(266) Rao, J. S.; Sastry, G. N. Structural and Energetic Preferences of π,
σ, and Bidentate Cation Binding (Li+, Na+, and Mg2+) to Aromatic
Amines (Ph-(CH2)n-NH2, n = 2−5): A Theoretical Study. J. Phys. Chem.
A 2009, 113, 5446−5454.
(267) Srivastava, H. K.; Sastry, G. N. Viability of Clathrate Hydrates as
CO2 Capturing Agents: A Theoretical Study. J. Phys. Chem. A 2011, 115,
7633−7637.
(268) Dinadayalane, T. C.; Sastry, G. N.; Leszczynski, J.
Comprehensive Theoretical Study Towards the Accurate Proton
Affinity Values of Naturally Occurring Amino Acids. Int. J. Quantum
Chem. 2006, 106, 2920−2933.
(269) Kumar, M. K.; Rao, J. S.; Prabhakar, S.; Vairamani, M.; Sastry, G.
N. The Effect of Spacer Chain Length on Ion Binding to Bidentate α, ω-
diamines: Contrasting Ordering for H+ and Li+ ion affinities. Chem.
Commun. 2005, 1420−1422.
(270) Reddy, A. S.; Vijay, D.; Sastry, G. M.; Sastry, G. N. From Subtle
to Substantial: Role of Metal Ions on π-π Interactions. J. Phys. Chem. B
2006, 110, 2479−2481.
(271) Reddy, A. S.; Vijay, D.; Sastry, G. M.; Sastry, G. N. Reply to
“Comment on ‘From Subtle to Substantial: Role of Metal Ions on π-π
Interactions’. J. Phys. Chem. B 2006, 110, 10206−10207.
(272) Purushotham, U.; Sastry, G. N. A Comprehensive Conforma-
tional Analysis of Tryptophan, its Ionic and Dimeric Forms. J. Comput.
Chem. 2014, 35, 595−610.
(273) Purushotham, U.; Sastry, G. N. Exploration of Conformations
and Quantum Chemical Investigation of L-Tyrosine Dimers, Anions,
Cations and Zwitterions: a DFT study. Theor. Chem. Acc. 2012, 131,
1093−14.
(274) Purushotham, U.; Vijay, D.; Sastry, G. N. A Computational
Investigation and the Conformational Analysis of Dimers, Anions,
Cations, and Zwitterions of L-Phenylalanine. J. Comput. Chem. 2012, 33,
44−59.
(275) Saha, S.; Sastry, G. N. Cooperative or Anticooperative: How
Non-covalent Interactions Influence Each Other. J. Phys. Chem. B 2015,
119, 11121−11135.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(276) Sharma, B.; Srivastava, H. K.; Gayatri, G.; Sastry, G. N. Energy
Decomposition Analysis of Cation-π, Metal Ion-Lone Pair, Hydrogen
Bonded, Charge Assisted Hydrogen Bonded and π-π Interactions. J.
Comput. Chem. 2015, 36, 529−538.
(277) Hussain, M. A.; Mahadevi, A. S.; Sastry, G. N. Estimating the
Binding Ability of Onium Ions with CO2 and π Systems: A
Computational Investigation. Phys. Chem. Chem. Phys. 2015, 17,
1763−1775.
(278) Neela, Y. I.; Sastry, G. N. Theoretical Investigation of Anion (F−,
Cl−) and Cation (Na+) Interactions with Substituted Benzene
[C6H6‑nYn (Y = -F, -CN, -NO2; n = 1−6)]. Mol. Phys. 2015, 113,
137−148.
(279) Biot, C.; Wintjens, R.; Rooman, M. Stair Motifs at Protein-DNA
Interfaces: Nonadditivity of H-Bond, Stacking, and Cation-π
Interactions. J. Am. Chem. Soc. 2004, 126, 6220−6221.
(280) Perraud, O.; Robert, V.; Gornitzka, H.; Martinez, A.; Dutasta, J.
Combined Cation−π and Anion−π Interactions for Zwitterion
Recognition. Angew. Chem., Int. Ed. 2012, 51, 504−508.
(281) Li, R.; Li, Q.; Cheng, J.; Liu, Z.; Li, W. The Prominent Enhancing
Effect of the Cation−π Interaction on the Halogen−Hydride Halogen
Bond in M1···C6H5X···HM2. ChemPhysChem 2011, 12, 2289−2295.
(282) Li, Q.; Li, W.; Cheng, J.; Gong, B.; Sun, J. Effect of Methyl Group
on the Cooperativity between Cation−π Interaction and NH···O
Hydrogen Bonding. J. Mol. Struct.: THEOCHEM 2008, 867, 107−110.
(283) Li, Q.; Li, R.; Liu, X.; Cheng, J.; Li, W. Ab initio Study of
Synergetic Effects of Two Strong Interactions of Cation−π Interaction
and Lithium Bond in M+ ··· Phenyl Lithium ··· N (M = Li, Na, K; N =
H2O and NH3) Complex. Mol. Phys. 2012, 110, 457−465.
(284) Lu, Y.; Liu, Y.; Li, H.; Zhu, X.; Liu, H.; Zhu, W. Mutual Influence
between Halogen Bonds and Cation−π Interactions: A Theoretical
Study. ChemPhysChem 2012, 13, 2154−2161.
(285) Duan, M.; Song, B.; Shi, G.; Li, H.; Ji, G.; Hu, J.; Chen, X.; Fang,
H. Cation⊗3π: Cooperative Interaction of a Cation and Three
Benzenes with an Anomalous Order in Binding Energy. J. Am. Chem.
Soc. 2012, 134, 12104−12109.
(286) Estarellas, C.; Frontera, A.; Quiñonero, D.; Deyà, P. M. Interplay
between Cation−π and Hydrogen Bonding Interactions: Are Non-
Additivity Effects Additive? Chem. Phys. Lett. 2009, 479, 316−320.
(287) Estarellas, C.; Frontera, A.; Quiñonero, D.; Deyà, P. M. Can
Lone Pair-π and Cation-π Interactions Coexist? A Theoretical Study.
Cent. Eur. J. Chem. 2011, 9, 25−34.
(288) Yan, Y.; Shi, W.; Feng, G.; Ren, F.; Wang, Y. A B3LYP and
MP2(full) Theoretical Investigation on the Cooperativity Effect
between Cation−Molecule and Hydrogen-Bonding Interactions in the
O-Cresol Complex with Na+. Comput. Theor. Chem. 2012, 996, 91−102.
(289) Li, B.; Shi, W.; Ren, F. A B3LYP and MP2 Theoretical
Investigation on the Cooperativity Effect between the XH···HM
(X = F, Cl, Br; M = Li, Na, K) Dihydrogen-Bonding and HM···π
Interactions Involving C6H6. Comput. Theor. Chem. 2013, 1020, 81−90.
(290) Zeng, Y.; Wu, W.; Li, X.; Zheng, S.; Meng, L. Influence of the
Li···π Interaction on the H/X···π Interactions in HOLi···C6H6···HOX/
XOH (X = F, Cl, Br, I) Complexes. ChemPhysChem 2013, 14, 1591−
1600.
(291) Ebrahimi, A.; Masoodi, H. R.; Khorassani, M. H.; Ghaleno, M. H.
The Influence of Cation-π and Anion-π Interactions on the Strength and
Nature of N···H Hydrogen Bond. Comput. Theor. Chem. 2012, 988, 48−
55.
(292) Esrafili, M. D.; Esmailpour, P.; Mohammadian-Sabet, F.;
Solimannejad, M. Theoretical Study of the Interplay between Halogen
Bond and Lithium−π Interactions: Cooperative and Diminutive Effects.
Chem. Phys. Lett. 2013, 588, 47−50.
(293) Frontera, A.; Quiñonero, D.; Garau, C.; Costa, A.; Ballester, P.;
Deyà, P. M. MP2 Study of Cation−(π)n−π Interactions (n = 1−4). J.
Phys. Chem. A 2006, 110, 9307−9309.
(294) Frontera, A.; Quiñonero, D.; Costa, A.; Ballester, P.; Deyá, P. M.
MP2 Study of Cooperative Effects between Cation−π, Anion−π and
π−π interactions. New J. Chem. 2007, 31, 556−560.
(295) Vasudevan, D.; Arey, T. A.; Dickstein, D. R.; Newman, M. H.;
Zhang, T. Y.; Kinnear, H. M.; Bader, M. M. Nonlinearity of Cationic
2813
Review
Aromatic Amine Sorption to Aluminosilicates and Soils: Role of
Intermolecular Cation−π Interactions. Environ. Sci. Technol. 2013, 47,
14119−14127.
(296) Song, J.; Ng, S. C.; Tompa, P.; Lee, K. A. W.; Chan, H. S.
Polycation-π Interactions Are a Driving Force for Molecular
Recognition by an Intrinsically Disordered Oncoprotein Family. PLoS
Comput. Biol. 2013, 9, e1003239−12.
(297) Dimitrijević, B. P.; Borozan, S. Z.; Stojanović, S. Đ. π−π and
Cation−π Interactions in Protein−Porphyrin Complex Crystal
Structures. RSC Adv. 2012, 2, 12963−12972.
(298) Francisco, V.; Basílio, N.; García-Río, L. Ionic Exchange in p-
Sulfonatocalix[4]arene-Mediated Formation of Metal−Ligand Com-
plexes. J. Phys. Chem. B 2014, 118, 4710−4716.
(299) Feng, G.; Qi, T.; Shi, W.; Guo, Y.; Zhang, Y.; Guo, J.; Kang, L. A
B3LYP and MP2(full) Theoretical Investigation on the Cooperativity
Effect between Hydrogen-Bonding and Cation-Molecule Interactions
and Thermodynamic Property in the 1:2 (Na+:N-(Hydroxymethyl)-
acetamide) Ternary Complex. J. Mol. Model. 2014, 20, 2154.
(300) Zhang, D.; Chatelet, B.; Serrano, E.; Perraud, O.; Dutasta, J.;
Robert, V.; Martinez, A. Insights into the Complexity of Weak
Intermolecular Interactions Interfering in Host−Guest Systems.
ChemPhysChem 2015, 16, 2931−2935.
(301) Li, Y.; Pink, M.; Karty, J. A.; Flood, A. H. Dipole-Promoted and
Size-Dependent Cooperativity between Pyridyl-Containing Triazolo-
phanes and Halides Leads to Persistent Sandwich Complexes with
Iodide. J. Am. Chem. Soc. 2008, 130, 17293−17295.
(302) Hall, B. R.; Manck, L. E.; Tidmarsh, I. S.; Stephenson, A.; Taylor,
B. F.; Blaikie, E. J.; Griend, D. A. V.; Ward, M. D. Structures, Host−
Guest Chemistry and Mechanism of Stepwise Self-Assembly of M4L6
Tetrahedral Cage Complexes. Dalton Trans. 2011, 40, 12132−12145.
(303) Quiñonero, D.; Deyà, P. M.; Carranza, M. P.; Rodríguez, A. M.;
Jalón, F. A.; Manzano, B. R. Experimental and Computational Study of
the Interplay between C−H/π and Anion−π Interactions. Dalton Trans.
2010, 39, 794−806.
(304) Notash, B.; Safari, N.; Khavasi, H. R. Anion-Controlled
Structural Motif in One-Dimensional Coordination Networks via
Cooperative Weak Noncovalent Interactions. CrystEngComm 2012, 14,
6788−6796.
(305) Arcus, V.; Bernstein, D.; Crombie, C.; Saunders, G. Infinite
Stacking of Alternating Polyfluoroaryl Rings and Bromide Anions.
CrystEngComm 2013, 15, 9841−9843.
(306) Hay, B. P.; Bryantsev, V. S. Anion−Arene Adducts: C−H
Hydrogen Bonding, Anion−π Interaction, and Carbon Bonding Motifs.
Chem. Commun. 2008, 2417−2428.
(307) Manzano, B. R.; Jalón, F. A.; Ortiz, I. M.; Soriano, M. L.; de la
Torre, F. G.; Elguero, J.; Maestro, M. A.; Mereiter, K.; Claridge, T. D. W.
Self-Assembly of Ligands Designed for the Building of a New Type of [2
× 2] Metallic Grid. Anion Encapsulation and Diffusion NMR
Spectroscopy. Inorg. Chem. 2008, 47, 413−428.
(308) Garcia-Raso, A.; Albertí, F. M.; Fiol, J. J.; Tasada, A.; Barceló-
Oliver, M.; Molins, E.; Escudero, D.; Frontera, A.; Quiñonero, D.; Deyà,
P. M. Anion-π Interactions in Bisadenine Derivatives: A Combined
Crystallographic and Theoretical Study. Inorg. Chem. 2007, 46, 10724−
10735.
(309) Berryman, O. B.; Johnson, D. W. Experimental Evidence for
Interactions between Anions and Electron-Deficient Aromatic Rings.
Chem. Commun. 2009, 3143−3153.
(310) Berryman, O. B.; Hof, F.; Hynes, M. J.; Johnson, D. W. Anion−π
Interaction Augments Halide Binding in Solution. Chem. Commun.
2006, 506−508.
(311) Jentzsch, A. V.; Emery, D.; Mareda, J.; Metrangolo, P.; Resnati,
G.; Matile, S. Ditopic Ion Transport Systems: Anion−π Interactions and
Halogen Bonds at Work. Angew. Chem., Int. Ed. 2011, 50, 11675−11678.
(312) Giese, M.; Albrecht, M.; Krappitz, T.; Peters, M.; Gossen, V.;
Raabe, G.; Valkonen, A.; Rissanen, K. Cooperativity of H-bonding and
Anion−π Interaction in the Binding of Anions with Neutral π-
Acceptors. Chem. Commun. 2012, 48, 9983−9985.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(313) Zaccheddu, M.; Filippi, C.; Buda, F. Anion-π and π-π
Cooperative Interactions Regulating the Self-Assembly of Nitrate-
Triazine-Triazine Complexes. J. Phys. Chem. A 2008, 112, 1627−1632.
(314) Gural’skiy, I. A.; Escudero, D.; Frontera, A.; Solntsev, P. V.;
Rusanov, E. B.; Chernega, A. N.; Krautscheid, H.; Domasevitch, K. V.
1,2,4,5-Tetrazine: An Unprecedented μ4-Coordination that Enhances
Ability for Anion···π Interactions. Dalton Trans. 2009, 2856−2864.
(315) Quiñonero, D.; Frontera, A.; Garau, C.; Ballester, P.; Costa, A.;
Deyá, P. M. Interplay Between Cation−π, Anion− π and π−π
Interactions. ChemPhysChem 2006, 7, 2487−2491.
(316) Lucas, X.; Estarellas, C.; Escudero, D.; Frontera, A.; Quiñonero,
D.; Deyà, P. M. Very Long-Range Effects: Cooperativity between
Anion−π and Hydrogen-Bonding Interactions. ChemPhysChem 2009,
10, 2256−2264.
(317) Estarellas, C.; Frontera, A.; Quiñonero, D.; Deyà, P. M.
Theoretical Study on Cooperativity Effects between Anion−π and
Halogen-Bonding Interactions. ChemPhysChem 2011, 12, 2742−2750.
(318) Estarellas, C.; Frontera, A.; Quiñonero, D.; Deyà, P. M.
Unexpected Nonadditivity Effects in Anionπ Complexes. J. Phys.
Chem. A 2011, 115, 7849−7857.
(319) Estarellas, C.; Frontera, A.; Quiñonero, D.; Alkorta, I.; Deyà, P.
M.; Elguero, J. Energetic vs Synergetic Stability: A Theoretical Study. J.
Phys. Chem. A 2009, 113, 3266−3273.
(320) Alkorta, I.; Blanco, F.; Elguero, J. Simultaneous Interaction of
Tetrafluoroethene with Anions and Hydrogen-Bond Donors: A
Cooperativity Study. J. Chem. Theory Comput. 2009, 5, 1186−1194.
(321) Alkorta, I.; Blanco, F.; Deyá, P. M.; Elguero, J.; Estarellas, C.;
Frontera, A.; Quiñonero, D. Cooperativity in Multiple Unusual Weak
Bonds. Theor. Chem. Acc. 2010, 126, 1−14.
(322) Escudero, D.; Frontera, A.; Quiñonero, D.; Deyà, P. M. Interplay
between Anion-π and Hydrogen Bonding Interactions. J. Comput. Chem.
2009, 30, 75−82.
(323) Kumbhar, S.; Jana, S.; Anoop, A.; Waller, M. P. Cooperativity in
Bimetallic Glutathione Complexes. J. Mol. Graphics Modell. 2015, 62, 1−
10.
(324) Zeng, Y.; Hao, J.; Zheng, S.; Meng, L. Cooperativity between
S···π and Rg···π in the OCS···C6H6···Rg (Rg = He, Ne, Ar, and Kr) van
der Waals Complexes. J. Phys. Chem. A 2011, 115, 11057−11066.
(325) Hua, S.; Xu, L.; Li, W.; Li, S. Cooperativity in Long α- and 310-
Helical Polyalanines: Both Electrostatic and van der Waals Interactions
Are Essential. J. Phys. Chem. B 2011, 115, 11462−11469.
(326) Mück-Lichtenfeld, C.; Grimme, S. Theoretical Analysis of
Cooperative Effects of Small Molecule Activation by Frustrated Lewis
Pairs. Dalton Trans. 2012, 41, 9111−9118.
(327) Solimannejad, M.; Ghafari, S.; Esrafili, M. D. Theoretical Insight
into Cooperativity in Lithium-Bonded Complexes: Linear Clusters of
LiCN and LiNC. Chem. Phys. Lett. 2013, 577, 6−10.
(328) Alkorta, I.; Blanco, F.; Elguero, J. A Computational Study of the
Cooperativity in Clusters of Interhalogen Derivatives. Struct. Chem.
2009, 20, 63−71.
(329) Ghoshal, D.; Maji, T. K. Fabrication of Supramolecular
Frameworks by Tuning the Binding Site of a Tripodal Ligand with d10
Metal Ions: Interplay of Covalent and Noncovalent Interactions in
Solid-State Structure. J. Chem. Sci. 2010, 122, 801−806.
(330) Lv, H.; Zhuo, H.; Li, Q.; Yang, X.; Li, W.; Cheng, J. Mutual
Influence between Covalent and Noncovalent Interactions in H3N−
MCN−XF (X = H, Li, Cl, Br; M = Ag, Cu, Au). Mol. Phys. 2014, 112,
1081−1088.
(331) Esrafili, M. D.; Esmailpour, P.; Mohammadian-Sabet, F.;
Solimannejad, M. Substituent Effects on Cooperativity between Lithium
Bonds. Int. J. Quantum Chem. 2014, 114, 295−301.
(332) Esrafili, M. D.; Fatehi, P.; Solimannejad, M. Mutual Influence
between Conventional and Unconventional Lithium Bonds. J. Mol.
Graphics Modell. 2014, 49, 129−137.
(333) Esrafili, M. D.; Vakili, M. Halogen Bonds Enhanced by σ-hole
and π-hole Interactions: A Comparative Study on Cooperativity and
Competition Effects between X···N and S···N Interactions in H3N···
XCN···SF2 and H3N···XCN···SO2 Complexes (X = F, Cl, Br and I). J.
Mol. Model. 2014, 20, 1−9.
2814
Review
(334) Solimannejad, M.; Malekani, M.; Alkorta, I. Cooperative and
Diminutive Unusual Weak Bonding In F3CX···HMgH···Y and F3CX···
Y···HMgH Trimers (X = Cl, Br; Y = HCN, and HNC). J. Phys. Chem. A
2010, 114, 12106−12111.
(335) Zhao, Q.; Feng, D.; Hao, J. The Cooperativity between
Hydrogen and Halogen Bond in the XY···HNC···XY (X, Y = F, Cl, Br)
complexes. J. Mol. Model. 2011, 17, 2817−2823.
(336) McDowell, S. A. C.; Joseph, J. A. Cooperative Effects of
Noncovalent Bonds to the Br Atom of Halogen-Bonded H3N···BrZ and
HCN···BrZ (Z = F, Br) Complexes. J. Chem. Phys. 2012, 137, 074310−8.
(337) McDowell, S. A. C.; Joseph, J. A. Cooperative Effects in Novel
LiF/HFLiFXF (X = F, Cl, Br) Clusters. J. Chem. Phys. 2013, 138,
164313−5.
(338) Wu, W.; Lu, Y.; Liu, Y.; Li, H.; Peng, C.; Liu, H.; Zhu, W. Weak
Energetic Effects between X−π and X−N Halogen Bonds: CSD Search
and Theoretical Study. Chem. Phys. Lett. 2013, 582, 49−55.
(339) Mitra, M.; Manna, P.; Seth, S. K.; Das, A.; Meredith, J.; Helliwell,
M.; Bauzá, A.; Choudhury, S. R.; Frontera, A.; Mukhopadhyay, S. Salt-
bridge−π (sb−π) Interactions at Work: Associative Interactions of
sb−π, π−π and Anion−π in Cu(II)-malonate−2-aminopyridine−
hexafluoridophosphate Ternary System. CrystEngComm 2013, 15,
686−696.
(340) Albrecht, L.; Boyd, R. J.; Mó, O.; Yáñez, M. Changing Weak
Halogen Bonds into Strong Ones through Cooperativity with Beryllium
Bonds. J. Phys. Chem. A 2014, 118, 4205−4213.
(341) An, X.; Li, R.; Li, Q.; Liu, X.; Li, W.; Cheng, J. Substitution,
Cooperative, and Solvent Effects on π Pnicogen Bonds in the FH2P and
FH2As Complexes. J. Mol. Model. 2012, 18, 4325−4332.
(342) Li, Q.; Sun, L.; Liu, X.; Li, W.; Cheng, J.; Zeng, Y. Enhancement
of Iodine−Hydride Interaction by Substitution and Cooperative Effects
in NCX−NCI−HMY Complexes. ChemPhysChem 2012, 13, 3997−
4002.
(343) Suresh, C. H.; Mohan, N.; Vijayalakshmi, K. P.; George, R.;
Mathew, J. M. Typical Aromatic Noncovalent Interactions in Proteins:
A Theoretical Study Using Phenylalanine. J. Comput. Chem. 2009, 30,
1392−1404.
(344) Podgornik, R.; French, R. H.; Parsegian, V. A. Nonadditivity in
van der Waals Interactions within Multilayers. J. Chem. Phys. 2006, 124,
044709.
(345) Alkorta, I.; Elguero, J.; Yáñez, M.; Mó, O. Cooperativity in
Beryllium Bonds. Phys. Chem. Chem. Phys. 2014, 16, 4305−4312.
(346) Xu, T.; Chen, E. Y. -X. Probing Site Cooperativity of Frustrated
Phosphine/Borane Lewis Pairs by a Polymerization Study. J. Am. Chem.
Soc. 2014, 136, 1774−1777.
(347) Malenov, D. P.; Janjić, G. V.; Veljković, D. Ž .; Zarić, S. D. Mutual
Influence of Parallel, CH/O, OH/π and Lone Pair/π Interactions in
Water/Benzene/Water System. Comput. Theor. Chem. 2013, 1018, 59−
65.
(348) Wang, Y.; Wu, W.; Liu, Y.; Lu, Y. Influence of Transition Metal
Coordination on Halogen Bonding: CSD Survey and Theoretical Study.
Chem. Phys. Lett. 2013, 578, 38−42.
(349) Campo-Cacharrón, A.; Cabaleiro-Lago, E. M.; Carrazana-
García, J. A.; Rodríguez-Otero, J. Interaction of Aromatic Units of
Amino Acids with Guanidinium Cation: The Interplay of π···π, X
H···π, and M+···π Contacts. J. Comput. Chem. 2014, 35, 1290−1301.
(350) Yu, G.; Hua, B.; Han, C. Proton Transfer in Host−Guest
Complexation between a Difunctional Pillar[5]arene and Alkyldi-
amines. Org. Lett. 2014, 16, 2486−2489.
(351) George, J.; Deringer, V. L.; Dronskowski, R. Cooperativity of
Halogen, Chalcogen, and Pnictogen Bonds in Infinite Molecular Chains
by Electronic Structure Theory. J. Phys. Chem. A 2014, 118, 3193−3200.
(352) Gunning, P. T. Positive Ion Pair Cooperativity Exhibited for the
Binding of Phosphate under Physiological Conditions. Org. Biomol.
Chem. 2005, 3, 3877−3879.
(353) Burress, C. N.; Bodine, M. I.; Elbjeirami, O.; Reibenspies, J. H.;
Omary, M. A.; Gabbaï, F. P. Enhancement of External Spin-Orbit
Coupling Effects Caused by Metal-Metal Cooperativity. Inorg. Chem.
2007, 46, 1388−1395.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(354) Kuriakose, N.; Kadam, S.; Vanka, K. A Theoretical Study of
Metal−Metal Cooperativity in the Homogeneous Water Gas Shift
Reaction. Inorg. Chem. 2012, 51, 377−385.
(355) Medel, R.; Heger, M.; Suhm, M. A. Molecular Docking via
Olefinic OH···π Interactions: A Bulky Alkene Model System and Its
Cooperativity. J. Phys. Chem. A 2015, 119, 1723−1730.
(356) Marín-Luna, M.; Alkorta, I.; Elguero, J.; Mó, O.; Yáñez, M.
Interplay between Beryllium Bonds and Anion-π Interactions in
BeR2:C6X6:Y− Complexes (R = H, F and Cl, X = H and F, and Y =
Cl and Br). Molecules 2015, 20, 9961−9976.
(357) Guo, X.; An, X.; Li, Q. Se···N Chalcogen Bond and Se···X
Halogen Bond Involving F2CSe: Influence of Hybridization,
Substitution, and Cooperativity. J. Phys. Chem. A 2015, 119, 3518−3527.
(358) Gao, M.; Cheng, J.; Yang, X.; Li, W.; Xiao, B.; Li, Q. Influence of
Substituents on the Nature of Metal···π Interaction and its
Cooperativity with Halogen Bond. J. Chem. Phys. 2015, 143, 054308−7.
(359) Ghafari, S.; Gholipour, A. Simultaneous Interactions of
Pyrimidine Ring with BeF2 and BF3 in BeF2···X−Pyr···BF3 Complexes:
Non-cooperativity. J. Mol. Model. 2015, 21, 253.
(360) Marín-Luna, M.; Alkorta, I.; Elguero, J.; Mó, O.; Yáñez, M.
Simultaneous Aromatic−Beryllium Bonds and Aromatic−Anion
Interactions: Naphthalene and Pyrene as Models of Fullerenes, Carbon
Single-Walled Nanotubes, and Graphene. ChemPhysChem 2015, 16,
2680−2686.
(361) Varadwaj, P. R.; Varadwaj, A.; Jin, B. Unusual Bonding Modes of
Perfluorobenzene in its Polymeric (Dimeric, Trimeric and Tetrameric)
Forms: Entirely Negative Fluorine Interacting Cooperatively with
Entirely Negative Fluorine. Phys. Chem. Chem. Phys. 2015, 17, 31624.
(362) Fokin, A. A.; Gerbig, D.; Schreiner, P. R. σ/σ- and π/π-
Interactions Are Equally Important: Multilayered Graphanes. J. Am.
Chem. Soc. 2011, 133, 20036−20039.
(363) Schreiner, P. R.; Chernish, L. V.; Gunchenko, P. A.; Tikhonchuk,
E. Y.; Hausmann, H.; Serafin, M.; Schlecht, S.; Dahl, J. E. P.; Carlson, R.
M. K.; Fokin, A. A. Overcoming Lability of Extremely Long Alkane
Carbon−Carbon Bonds through Dispersion Forces. Nature 2011, 477,
308−312.
(364) Alonso, M.; Woller, T.; Martin-Martinez, F. J.; Contreras-García,
J.; Geerlings, P.; De Proft, F. Understanding the Fundamental Role of π/
π, σ/σ, and σ/π Dispersion Interactions in Shaping Carbon-Based
Materials. Chem. - Eur. J. 2014, 20, 4931−4941.
(365) Kemnitz, C. R.; Mackey, J. L.; Loewen, M. J.; Hargrove, J. L.;
Lewis, J. L.; Hawkins, W. E.; Nielsen, A. F. Origin of Stability in
Branched Alkanes. Chem. - Eur. J. 2010, 16, 6942−6949.
(366) Wodrich, M. D.; Wannere, C. S.; Mo, Y.; Jarowski, P. D.; Houk,
K. N.; von Rague Schleyer, P. The Concept of Protobranching and Its
Many Paradigm Shifting Implications for Energy Evaluations. Chem. -
Eur. J. 2007, 13, 7731−7744.
(367) Janowski, T.; Pulay, P. A Benchmark Comparison of σ/σ and π/
π Dispersion: The Dimers of Naphthalene and Decalin, and Coronene
and Perhydrocoronene. J. Am. Chem. Soc. 2012, 134, 17520−17525.
(368) Gonthier, J. F.; Wodrich, M. D.; Steinmann, S. N.; Corminboeuf,
C. Branched Alkanes Have Contrasting Stabilities. Org. Lett. 2010, 12,
3070−3073.
(369) Jiemchooroj, A.; Sernelius, B. E.; Norman, P. C6 Dipole-Dipole
Dispersion Coefficients for the n-Alkanes: Test of an Additivity
Procedure. Phys. Rev. A: At., Mol., Opt. Phys. 2004, 69, 044701.
(370) Hatano, B.; Aikawa, A.; Tagaya, H.; Takahashi, H. New
Approach for the Recovery of Bisphenol A from Water Using Inclusion
Complex with Quinoline Derivatives. Chem. Lett. 2004, 33, 1276−1277.
(371) Bourne, S. A.; Corin, K. C.; Nassimbeni, L. R.; Toda, F. Selective
Enclathration of Picolines. Cryst. Growth Des. 2005, 5, 379−382.
(372) Stoll, I.; Brodbeck, R.; Neumann, B.; Stammler, H.; Mattay, J.
Controlling the Self Assembly of Arene Functionalised 2-amino-
pyrimidines by arene-perfluoroarene Interaction and by Silver(I)
Complex Formation. CrystEngComm 2009, 11, 306−317.
(373) Fu, X.; Li, J.; Simpson, J. Non-Covalent Interactions in the
Crystal Structure of Methyl 4-Hydroxy-3-Nitrobenzoate. Crystals 2012,
2, 669−674.
2815
Review
(374) Dey, S. K.; Das, G. Selective inclusion of PO43− within Persistent
Dimeric Capsules of a Tris(thiourea) Receptor and Evidence of Cation/
Solvent Sealed Unimolecular Capsules. Dalton Trans. 2012, 41, 8960−
8972.
(375) Zaman, I. G.; Delibas, N. C.; Necefoğlu, H.; Hökelek, T. trans-
Tetraaquabis(isonicotinamide-κN1)zinc bis(3-hydroxybenzoate) tetra-
hydrate. Acta Crystallogr., Sect. E: Struct. Rep. Online 2013, 69, m198−
m199.
(376) Al-Mawsawi, L. Q.; Hombrouck, A.; Dayam, R.; Debyser, Z.;
Neamati, N. Four-Tiered π Interaction at the Dimeric Interface of HIV-
1 Integrase Critical for DNA Integration and Viral Infectivity. Virology
2008, 377, 355−363.
(377) Degtyarenko, A. S.; Domasevitch, K. V. Cadmium(II) Iodide
and Thiocyanate Complexes Adopted by Polycyclic 1,4-bis(pyridazin-4-
yl)benzene: Interplay of Coordination and π−π Stacking Interactions.
Acta Crystallogr., Sect. C: Cryst. Struct. Commun. 2013, 69, 219−224.
(378) Walter, S. M.; Sarwar, M. G.; Chudzinski, M. G.; Herdtweck, E.;
Lough, A. J.; Huber, S. M.; Taylor, M. S. Halogen Bonding and π−π
Interactions in the Solid-State Structure of a Butadiynylene-Linked
Bis(iodoperfluoroarene). CrystEngComm 2013, 15, 3097−3101.
(379) Shishkin, O. V.; Medvediev, V. V.; Zubatyuk, R. I. Supra-
molecular Architecture of Molecular Crystals Possessing Shearing
Mechanical Properties: Columns versus Layers. CrystEngComm 2013,
15, 160−167.
(380) Chen, J.; Lai, Y.; Wan, D.; Jin, M.; Pu, H. Cooperative
Entrapment of Xanthene Dyes by a Core-Engineered Unimolecular
Micelle. Macromol. Chem. Phys. 2013, 214, 1817−1828.
(381) Eryazici, I.; Moorefield, C. N.; Durmus, S.; Newkome, G. R.
Synthesis and Single-Crystal X-ray Characterization of 4,4″-Function-
alized 4′-(4-Bromophenyl)-2,2′:6′,2″-terpyridines. J. Org. Chem. 2006,
71, 1009−1014.
(382) Britton, D. o-Chloro- and o-bromobenzo-nitrile: Pseudosym-
metry and Pseudo-Isostructural Packing. Acta Crystallogr., Sect. C: Cryst.
Struct. Commun. 2007, 63, o14−o16.
(383) Vijay, D.; Sakurai, H.; Sastry, G. N. The Impact of Basis Set
Superposition Error on the Structure of π-π Dimers. Int. J. Quantum
Chem. 2011, 111, 1893−1901.
(384) Mignon, P.; Loverix, S.; De Proft, F.; Geerlings, P. Influence of
Stacking on Hydrogen Bonding: Quantum Chemical Study on Pyridine-
Benzene Model Complexes. J. Phys. Chem. A 2004, 108, 6038−6044.
(385) Gray, M.; Goodman, A. J.; Carroll, J. B.; Bardon, K.; Markey, M.;
Cooke, G.; Rotello, V. M. Model Systems for Flavoenzyme Activity:
Interplay of Hydrogen Bonding and Aromatic Stacking in Cofactor
Redox Modulation. Org. Lett. 2004, 6, 385−388.
(386) Hesselmann, A.; Jansen, G.; Schütz, M. Interaction Energy
Contributions of H-Bonded and Stacked Structures of the AT and GC
DNA Base Pairs from the Combined Density Functional Theory and
Intermolecular Perturbation Theory Approach. J. Am. Chem. Soc. 2006,
128, 11730−11731.
(387) Santos, J.; Grimm, B.; Illescas, B. M.; Guldi, D. M.; Martín, N.
Cooperativity between π-π and H-Bonding Interactions−A Supra-
molecular Complex Formed by C60 and exTTF. Chem. Commun. 2008,
5993−5995.
(388) Escudero, D.; Frontera, A.; Quiñonero, D.; Deya, P. M. Interplay
between Edge-to-Face Aromatic and Hydrogen-Bonding Interactions. J.
Phys. Chem. A 2008, 112, 6017−6022.
(389) Quiñonero, D.; Frontera, A.; Escudero, D.; Ballester, P.; Costa,
A.; Deyà, P. M. MP2 Study of Synergistic Effects between X−H/π (X =
C,N,O) and π−π Interactions. Theor. Chem. Acc. 2008, 120, 385−393.
(390) Estarellas, C.; Escudero, D.; Frontera, A.; Quiñonero, D.; Deya,
P. M. Theoretical Ab Initio Study of the Interplay between Hydrogen
Bonding, Cation−π and π−π Interactions. Theor. Chem. Acc. 2009, 122,
325−332.
(391) Ebrahimi, A.; Habibi, M.; Neyband, R. S.; Gholipour, A. R.
Cooperativity of π-Stacking and Hydrogen Bonding Interactions and
Substituent Effects on X-ben∥pyr···H−F Complexes. Phys. Chem. Chem.
Phys. 2009, 11, 11424−11431.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(392) Kulkarni, C.; Reddy, S. K.; George, S. J.; Balasubramanian, S.
Cooperativity in the Stacking of Benzene-1, 3, 5-Tricarboxamide: The
Role of Dispersion. Chem. Phys. Lett. 2011, 515, 226−230.
(393) Ninković, D. B.; Janjić, G. V.; Zarić, S. D. Crystallographic and
Ab Initio Study of Pyridine Stacking Interactions. Local Nature of
Hydrogen Bond Effect in Stacking Interactions. Cryst. Growth Des. 2012,
12, 1060−1063.
(394) Li, H.; Lu, Y.; Liu, Y.; Zhu, X.; Liu, H.; Zhu, W. Interplay
between Halogen Bonds and π−π Stacking Interactions: CSD Search
and Theoretical Study. Phys. Chem. Chem. Phys. 2012, 14, 9948−9955.
(395) Muzangwa, L.; Nyambo, S.; Uhler, B.; Reid, S. A. On π-Stacking,
C-H/π, and Halogen Bonding Interactions in Halobenzene Clusters:
Resonant Two-Photon Ionization Studies of Chlorobenzene. J. Chem.
Phys. 2012, 137, 184307−9.
(396) Tam, A. Y.; Wong, K. M.; Wang, G.; Yam, V. W. Luminescent
Metallogels of Platinum(II) Terpyridyl Complexes: Interplay of
Metal···Metal, π−π and Hydrophobic−Hydrophobic Interactions on
Gel Formation. Chem. Commun. 2007, 20, 2028−2030.
(397) Tsuzuki, S.; Honda, K.; Uchimaru, T.; Mikami, M.; Tanabe, K.
Origin of Attraction and Directionality of the π/π Interaction: Model
Chemistry Calculations of Benzene Dimer Interaction. J. Am. Chem. Soc.
2002, 124, 104−112.
(398) Sinnokrot, M. O.; Sherrill, C. D. High-Accuracy Quantum
Mechanical Studies of π-π Interactions in Benzene Dimers. J. Phys.
Chem. A 2006, 110, 10656−10668.
(399) Tauer, T. P.; Sherrill, C. D. Beyond the Benzene Dimer: An
Investigation of the Additivity of π-π Interactions. J. Phys. Chem. A 2005,
109, 10475−10478.
(400) Gonzalez, C.; Lim, E. C. Ab Initio Study of the Intermolecular
Interactions in Small Benzene Clusters: The Equilibrium Structures of
Trimer, Tetramer, and Pentamer. J. Phys. Chem. A 2001, 105, 1904−
1908.
(401) Gonzalez, C.; Allison, T. C.; Lim, E. C. Hartree-Fock Dispersion
Probe of the Equilibrium Structures of Small Microclusters of Benzene
and Naphthalene: Comparison with Second-Order MØeller-Plesset
Geometries. J. Phys. Chem. A 2001, 105, 10583−10587.
(402) Ye, X.; Li, Z.; Wang, W.; Fan, K.; Xu, W.; Hua, Z. The Parallel
π−π Stacking: A Model Study with MP2 and DFT Methods. Chem. Phys.
Lett. 2004, 397, 56−61.
(403) Swart, M.; van der Wijst, T.; Fonseca Guerra, C.; Bickelhaupt, F.
M. π-π Stacking Tackled with Density Functional Theory. J. Mol. Model.
2007, 13, 1245−1257.
(404) Pullan, W. J. Structure Prediction of Benzene Clusters Using a
Genetic Algorithm. J. Chem. Inf. Model. 1997, 37, 1189−1193.
(405) Takeuchi, H. Novel Method for Geometry Optimization of
Molecular Clusters: Application to Benzene Clusters. J. Chem. Inf.
Model. 2007, 47, 104−109.
(406) Mahadevi, A. S.; Rahalkar, A.; Gadre, S. R.; Sastry, G. N. Ab Initio
Investigation of Benzene Clusters: Molecular Tailoring Approach. J.
Chem. Phys. 2010, 133, 164308−12.
(407) Chourasia, M.; Sastry, G. M.; Sastry, G. N. Aromatic−Aromatic
Interactions Database, A2ID: An Analysis of Aromatic π-Networks in
Proteins. Int. J. Biol. Macromol. 2011, 48, 540−552.
(408) Reid, S. A.; Nyambo, S.; Muzangwa, L.; Uhler, B. π-Stacking, C−
H/π, and Halogen Bonding Interactions in Bromobenzene and Mixed
Bromobenzene−Benzene Clusters. J. Phys. Chem. A 2013, 117, 13556−
13563.
(409) Yang, J.; Waller, M. P. A Systematic Approach to Identify
Cooperatively Bound Homotrimers. J. Phys. Chem. A 2013, 117, 174−
182.
(410) Rutledge, L. R.; Churchill, C. D. M.; Wetmore, S. D. A
Preliminary Investigation of the Additivity of π-π or π+-π Stacking and T-
Shaped Interactions between Natural or Damaged DNA Nucleobases
and Histidine. J. Phys. Chem. B 2010, 114, 3355−3367.
(411) Churchill, C. D. M.; Rutledge, L. R.; Wetmore, S. D. Effects of
the Biological Backbone on Stacking Interactions at DNA−Protein
Interfaces: The Interplay between the Backbone··· π and π··· π
Components. Phys. Chem. Chem. Phys. 2010, 12, 14515−14526.
2816
Review
(412) Meyer, M.; Albrecht-Gary, A.; Dietrich-Buchecker, C. O.;
Sauvage, J. π-π Stacking-Induced Cooperativity in Copper(I)
Complexes with Phenanthroline Ligands. Inorg. Chem. 1999, 38,
2279−2287.
(413) Engkvist, O.; Hobza, P.; Selzle, H. L.; Schlag, E. W. Benzene
Trimer and Benzene Tetramer: Structures and Properties Determined
by the Nonempirical Model (NEMO) Potential Calibrated from the
CCSD(T) Benzene Dimer Energies. J. Chem. Phys. 1999, 110, 5758−
5762.
(414) Iimori, T.; Ohshima, Y. S1−S0 Vibronic Spectra of Benzene
Clusters Revisited. I. The Tetramer. J. Chem. Phys. 2002, 117, 3656−
3674.
(415) Wolfenden, R.; Liang, Y.; Matthews, M.; Williams, R.
Cooperativity and Anticooperativity in Solvation by Water: Imidazoles,
Quinones, Nitrophenols, Nitrophenolate, and Nitrothiophenolate Ions.
J. Am. Chem. Soc. 1987, 109, 463−467.
(416) Lucht, B. L.; Collum, D. B. Lithium Ion Solvation: Amine and
Unsaturated Hydrocarbon Solvates of Lithium Hexamethyldisilazide
(LiHMDS). J. Am. Chem. Soc. 1996, 118, 2217−2225.
(417) Czaplewski, C.; Ripoll, D. R.; Liwo, A.; Rodziewicz-Motowidło,
S.; Wawak, R. J.; Scheraga, H. A. Can Cooperativity in Hydrophobic
Association Be Reproduced Correctly by Implicit Solvation Models? Int.
J. Quantum Chem. 2002, 88, 41−55.
(418) Robertson, W. H.; Karapetian, K.; Ayotte, P.; Jordan, K. D.;
Johnson, M. A. Infrared Predissociation Spectroscopy of I−.(CH3OH)n,
n = 1,2: Cooperativity in Asymmetric Solvation. J. Chem. Phys. 2002,
116, 4853−4857.
(419) Kar, T.; Scheiner, S. Cooperativity of Conventional and
Unconventional Hydrogen Bonds Involving Imidazole. Int. J. Quantum
Chem. 2006, 106, 843−851.
(420) Tarbuck, T. L.; Ota, S. T.; Richmond, G. L. Spectroscopic
Studies of Solvated Hydrogen and Hydroxide Ions at Aqueous Surfaces.
J. Am. Chem. Soc. 2006, 128, 14519−14527.
(421) Reddy, A. S.; Zipse, H.; Sastry, G. N. Cation-π Interactions of
Bare and Coordinatively Saturated Metal Ions: Contrasting Structural
and Energetic Characteristics. J. Phys. Chem. B 2007, 111, 11546−
11553.
(422) Rao, J. S.; Zipse, H.; Sastry, G. N. Explicit Solvent Effect on
Cation-π Interactions: A First Principle Investigation. J. Phys. Chem. B
2009, 113, 7225−7236.
(423) Rao, J. S.; Dinadayalane, T. C.; Sastry, G. N.; Leszczynski, J.
Comprehensive Study on the Solvation of Mono- and Divalent Metal
Cations: Li+, Na+, K+, Be2+, Mg2+ and Ca2+. J. Phys. Chem. A 2008, 112,
12944−12953.
(424) Neela, Y. I.; Mahadevi, A. S.; Sastry, G. N. First Principles Study
and Database Analyses of Structural Preferences for Sodium ion (Na+)
Solvation and Coordination. Struct. Chem. 2013, 24, 67−79.
(425) Neela, Y. I.; Mahadevi, A. S.; Sastry, G. N. Analyzing
Coordination Preferences of Mg2+ Complexes: Insights from Computa-
tional and Database Study. Struct. Chem. 2013, 24, 637−650.
(426) Bing, D.; Hamashima, T.; Fujii, A.; Kuo, J. Anticooperative Effect
Induced by Mixed Solvation in H+(CH3OH)m(H2O)n (m + n = 5 and
6): A Theoretical and Infrared Spectroscopic Study. J. Phys. Chem. A
2010, 114, 8170−8177.
(427) Tielrooij, K. J.; Garcia-Araez, N.; Bonn, M.; Bakker, H. J.
Cooperativity in Ion Hydration. Science 2010, 328, 1006−1009.
(428) Angelina, E. L.; Peruchena, N. M. Strength and Nature of
Hydrogen Bonding Interactions in Mono- and Di-Hydrated Formamide
Complexes. J. Phys. Chem. A 2011, 115, 4701−4710.
(429) Gao, Y. Q. Simple Theoretical Model for Ion Cooperativity in
Aqueous Solutions of Simple Inorganic Salts and Its Effect on Water
Surface Tension. J. Phys. Chem. B 2011, 115, 12466−12472.
(430) Li, Q.; Li, R.; Zhou, Z.; Li, W.; Cheng, J. S···X Halogen Bonds and
H···X Hydrogen Bonds in H2CS−XY (XY = FF, ClF, ClCl, BrF, BrCl,
and BrBr) Complexes: Cooperativity and Solvent Effect. J. Chem. Phys.
2012, 136, 014302−8.
(431) Sharma, B.; Rao, J. S.; Sastry, G. N. Effect of Solvation on Ion
Binding to Imidazole and Methylimidazole. J. Phys. Chem. A 2011, 115,
1971−1984.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(432) Miller, D. J.; Lisy, J. M. Entropic Effects on Hydrated Alkali-
Metal Cations: Infrared Spectroscopy and ab Initio Calculations of
M+(H2O)x=2−5 Cluster Ions for M = Li, Na, K, and Cs. J. Am. Chem. Soc.
2008, 130, 15393−15404.
(433) Prell, J. S.; O’Brien, J. T.; Williams, E. R. Structural and Electric
Field Effects of Ions in Aqueous Nanodrops. J. Am. Chem. Soc. 2011,
133, 4810−4818.
(434) Hishida, M.; Tanaka, K.; Yamamura, Y.; Saito, K. Cooperativity
between Water and Lipids in Lamellar to Inverted-Hexagonal Phase
Transition. J. Phys. Soc. Jpn. 2014, 83, 044801−8.
(435) Whitty, A. Cooperativity and Biological Complexity. Nat. Chem.
Biol. 2008, 4, 435−439.
(436) Editorial. Capturing Cooperativity. Nat. Chem. Biol. 2008, 4, 433.
(437) Williamson, J. R. Cooperativity in Macromolecular Assembly.
Nat. Chem. Biol. 2008, 4, 458−465.
(438) Eaton, W. A.; Henry, E. R.; Hofrichter, J.; Mozzarelli, A. Is
Cooperative Oxygen Binding by Hemoglobin Really Understood? Nat.
Struct. Biol. 1999, 6, 351−358.
(439) Hill, A. V. The Possible Effects of the Aggregation of the
Molecules of Haemoglobin on its Dissociation Curves. Proc. Physiol. Soc.
1910, 40, iv−vii.
(440) Haber, J. E.; Koshland, D. E., Jr. Relation of Protein Subunit
Interactions to the Molecular Species Observed During Cooperative
Binding Of Ligands. Proc. Natl. Acad. Sci. U. S. A. 1967, 58, 2087−2093.
(441) Ogata, R. T.; McConnell, H. M. Mechanism of Cooperative
Oxygen Binding to Hemoglobin. Proc. Natl. Acad. Sci. U. S. A. 1972, 69,
335−339.
(442) Lee, A. W.; Karplus, M. Structure-Specific Model of Hemoglobin
Cooperativity. Proc. Natl. Acad. Sci. U. S. A. 1983, 80, 7055−7059.
(443) Perutz, M. F. Mechanisms of cooperativity and allosteric
regulation in proteins. Q. Rev. Biophys. 1989, 22, 139−236.
(444) Monod, J.; Wyman, J.; Changeux, J. P. On the Nature of
Allosteric Transitions: A Plausible Model. J. Mol. Biol. 1965, 12, 88−118.
(445) Perutz, M. F. Stereochemistry of Cooperative Effects in
Haemoglobin. Nature 1970, 228, 726−734.
(446) Szabo, A.; Karplus, M. A Mathematical Model for Structure-
Function Relations in Hemoglobin. J. Mol. Biol. 1972, 72, 163−197.
(447) Ackers, G. K.; Doyle, M. L.; Myers, D.; Daugherty, M. A.
Molecular Code for Cooperativity in Hemoglobin. Science 1992, 255,
54−63.
(448) Changeux, J.; Thiéry, J.; Tung, Y.; Kittel, C. On the
Cooperativity of Biological Membranes. Proc. Natl. Acad. Sci. U. S. A.
1967, 57, 335−341.
(449) Hill, T. L. Electric Fields and the Cooperativity of Biological
Membranes. Proc. Natl. Acad. Sci. U. S. A. 1967, 58, 111−114.
(450) Rebek, J., Jr.; Wattley, R. V.; Costello, T.; Gadwood, R.;
Marshall, L. Allosteric Effects: Binding Cooperativity in a Subunit
Model. Angew. Chem., Int. Ed. Engl. 1981, 20, 605−606.
(451) Di Cera, E.; Gill, S. J.; Wyman, J. Binding Capacity:
Cooperativity and Buffering in Biopolymers. Proc. Natl. Acad. Sci. U. S.
A. 1988, 85, 449−452.
(452) Di Cera, E. Site-Specific Thermodynamics: Understanding
Cooperativity in Molecular Recognition. Chem. Rev. 1998, 98, 1563−
1592.
(453) Cui, Q.; Karplus, M. Allostery and Cooperativity Revisited.
Protein Sci. 2008, 17, 1295−1307.
(454) Cárdenas, M. L. Michaelis and Menten and the Long Road to the
Discovery of Cooperativity. FEBS Lett. 2013, 587, 2767−2771.
(455) Huang, H. W. Molecular Mechanism of Antimicrobial Peptides:
The Origin of Cooperativity. Biochim. Biophys. Acta, Biomembr. 2006,
1758, 1292−1302.
(456) Edelstein, S. A Novel Equation for Cooperativity of the
Allosteric State Function. J. Mol. Biol. 2014, 426, 39−42.
(457) Jencks, W. P. On the Attribution and Additivity of Binding
Energies. Proc. Natl. Acad. Sci. U. S. A. 1981, 78, 4046−4050.
(458) Tsai, C.; Nussinov, R. A Unified View of ‘‘How Allostery
Works’’. PLoS Comput. Biol. 2014, 10, e1003394−12.
(459) Bouhaddou, M.; Birtwistle, M. R. Dimerization-Based Control of
Cooperativity. Mol. BioSyst. 2014, 10, 1824−1832.
2817
Review
(460) Huma, Z. E.; Ludeman, J. P.; Wilkinson, B. L.; Payne, R. J.;
Stone, M. J. NMR Characterization of Cooperativity: Fast Ligand
Binding Coupled to Slow Protein Dimerization. Chem. Sci. 2014, 5,
2783−2788.
(461) Spassov, V.; Bashford, D. Electrostatic Coupling to pH-Titrating
Sites as a Source of Cooperativity in Protein-Ligand Binding. Protein Sci.
1998, 7, 2012−2025.
(462) Harris, S. A.; Gavathiotis, E.; Searle, M. S.; Orozco, M.;
Laughton, C. A. Cooperativity in Drug-DNA Recognition: A Molecular
Dynamics Study. J. Am. Chem. Soc. 2001, 123, 12658−12663.
(463) Jusuf, S.; Loll, P. J.; Axelsen, P. H. Configurational Entropy and
Cooperativity between Ligand Binding and Dimerization in Glycopep-
tide Antibiotics. J. Am. Chem. Soc. 2003, 125, 3988−3994.
(464) Jusuf, S.; Loll, P. J.; Axelsen, P. H. The Role of Configurational
Entropy in Biochemical Cooperativity. J. Am. Chem. Soc. 2002, 124,
3490−3491.
(465) Kawai, H.; Katoono, R.; Nishimura, K.; Matsuda, S.; Fujiwara,
K.; Tsuji, T.; Suzuki, T. Positive Homotropic Allosteric Binding of
Benzenediols in a Hydrindacene-Based Exoditopic Receptor: Cooper-
ativity in Amide Hydrogen Bonding. J. Am. Chem. Soc. 2004, 126, 5034−
5035.
(466) Schmuck, C.; Geiger, L. Efficient Complexation of N-Acetyl
Amino Acid Carboxylates in Water by an Artificial Receptor:
Unexpected Cooperativity in the Binding of Glutamate but Not
Aspartate. J. Am. Chem. Soc. 2005, 127, 10486−10487.
(467) Liu, T.; Whitten, S. T.; Hilser, V. J. Functional Residues Serve a
Dominant Role in Mediating the Cooperativity of the Protein Ensemble.
Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 4347−4352.
(468) Rieth, S.; Miner, M. R.; Chang, C. M.; Hurlocker, B.;
Braunschweig, A. B. Saccharide Receptor Achieves Concentration
Dependent Mannoside Selectivity through Two Distinct Cooperative
Binding Pathways. Chem. Sci. 2013, 4, 357−367.
(469) Goodey, N. M.; Benkovic, S. J. Allosteric Regulation and
Catalysis Emerge via a Common Route. Nat. Chem. Biol. 2008, 4, 474−
482.
(470) Masterson, L. R.; Mascioni, A.; Traaseth, N. J.; Taylor, S. S.;
Veglia, G. Allosteric Cooperativity in Protein Kinase A. Proc. Natl. Acad.
Sci. U. S. A. 2008, 105, 506−511.
(471) Li, G.; Srivastava, A. K.; Kim, J.; Taylor, S. S.; Veglia, G. Mapping
the Hydrogen Bond Networks in the Catalytic Subunit of Protein Kinase
A using H/D Fractionation Factors. Biochemistry 2015, 54, 4042−4049.
(472) Kremer, C.; Lützen, A. Artificial Allosteric Receptors. Chem. -
Eur. J. 2013, 19, 6162−6196.
(473) Dutta, S.; Weiner, L.; Sheves, M. Cation Binding to
Halorhodopsin. Biochemistry 2015, 54, 3164−3172.
(474) Yifrach, O.; Horovitz, A. Nested Cooperativity in the ATPase
Activity of the Oligomeric Chaperonin GroEL. Biochemistry 1995, 34,
5303−5308.
(475) Mammen, M.; Choi, S.; Whitesides, G. M. Polyvalent
Interactions in Biological Systems: Implications for Design and Use of
Multivalent Ligands and Inhibitors. Angew. Chem., Int. Ed. 1998, 37,
2754−2794.
(476) Falke, J. J. Cooperativity between Bacterial Chemotaxis
Receptors. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 6530−6532.
(477) Bialek, W.; Setayeshgar, S. Cooperativity, Sensitivity, and Noise
in Biochemical Signaling. Phys. Rev. Lett. 2008, 100, No. 258101.
(478) Chabre, M.; Deterre, P.; Antonny, B. The Apparent
Cooperativity of Some GPCRs Does Not Necessarily Imply
Dimerization. Trends Pharmacol. Sci. 2009, 30, 182−187.
(479) Sleat, D. E.; Wiseman, J. A.; El-Banna, M.; Price, S. M.; Verot, L.;
Shen, M. M.; Tint, G. S.; Vanier, M. T.; Walkley, S. U.; Lobel, P. Genetic
Evidence for Nonredundant Functional Cooperativity between NPC1
and NPC2 in Lipid Transport. Proc. Natl. Acad. Sci. U. S. A. 2004, 101,
5886−5891.
(480) Zandany, N.; Ovadia, M.; Orr, I.; Yifrach, O. Direct Analysis of
Cooperativity in Multisubunit Allosteric Proteins. Proc. Natl. Acad. Sci.
U. S. A. 2008, 105, 11697.
(481) Arnett, K. L.; Hass, M.; McArthur, D. G.; Ilagan, M. X. G.; Aster,
J. C.; Kopan, R.; Blacklow, S. C. Structural and Mechanistic Insights into
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
Cooperative Assembly of Dimeric Notch Transcription Complexes.
Nat. Struct. Mol. Biol. 2010, 17, 1312−1318.
(482) Patlak, J. B. Cooperating to Unlock the Voltage-dependent K
Channel. J. Gen. Physiol. 1999, 113, 385−387.
(483) Oana Popa, M.; Alekov, A. K.; Bail, S.; Lehmann-Horn, F.;
Lerche, H. Cooperative Effect of S4-S5 Loops in Domains D3 and D4
on Fast Inactivation of the Na+ Channel. J. Physiol. 2004, 561, 39−51.
(484) Pathak, M.; Kurtz, L.; Tombola, F.; Isacoff, E. The Cooperative
Voltage Sensor Motion that Gates a Potassium Channel. J. Gen. Physiol.
2004, 125, 57−69.
(485) Sack, J. T.; Aldrich, R. W. Binding of a Gating Modifier Toxin
Induces Intersubunit Cooperativity Early in the Shaker K Channel’s
Activation Pathway. J. Gen. Physiol. 2006, 128, 119−132.
(486) Nekouzadeh, A.; Silva, J. R.; Rudy, Y. Modeling Subunit
Cooperativity in Opening of Tetrameric Ion Channels. Biophys. J. 2008,
95, 3510−3520.
(487) Richards, M. J.; Gordon, S. E. Cooperativity and Cooperation in
Cyclic Nucleotide-Gated Ion Channels. Biochemistry 2000, 39, 14003−
14011.
(488) Meyer, T.; Holowka, D.; Stryer, L. Highly Cooperative Opening
of Calcium Channels by Inositol 1, 4, 5-Trisphosphate. Science 1988,
240, 653−656.
(489) Qian, X.; Niu, X.; Magleby, K. L. Intra- and Intersubunit
Cooperativity in Activation of BK Channels by Ca2+. J. Gen. Physiol.
2006, 128, 389−404.
(490) Smith-Maxwell, C. J.; Ledwell, J. L.; Aldrich, R. W. Role of the S4
in Cooperativity of Voltage-Dependent Potassium Channel Activation.
J. Gen. Physiol. 1998, 111, 399−420.
(491) Tombola, F.; Ulbrich, M. H.; Kohout, S. C.; Isacoff, E. Y. The
Opening of the Two Pores of the Hv1 Voltage-Gated Proton Channel is
Tuned by Cooperativity. Nat. Struct. Mol. Biol. 2010, 17, 44−50.
(492) Zhou, L. Ion Channels: Cooperativity in Twin Gatings. Nat.
Chem. Biol. 2012, 8, 136−137.
(493) Fujiwara, Y.; Kurokawa, T.; Takeshita, K.; Kobayashi, M.;
Okochi, Y.; Nakagawa, A.; Okamura, Y. The Cytoplasmic Coiled-Coil
Mediates Cooperative Gating Temperature Sensitivity in the Voltage-
Gated H+ Channel Hv1. Nat. Commun. 2012, 3, 816−11.
(494) Saito, M. Subunit Cooperativity in the Action of Lactate
Dehydrogenase. Biochim. Biophys. Acta 1972, 258, 17−26.
(495) Koshland, D. E., Jr.; Hamadani, K. Proteomics and Models for
Enzyme Cooperativity. J. Biol. Chem. 2002, 277, 46841−46844.
(496) Qian, H. Cooperativity and Specificity in Enzyme Kinetics: A
Single-Molecule Time-Based Perspective. Biophys. J. 2008, 95, 10−17.
(497) Levin, M. K.; Wang, Y.; Patel, S. S. The Functional Interaction of
the Hepatitis C Virus Helicase Molecules is Responsible for Unwinding
Processivity. J. Biol. Chem. 2004, 279, 26005−26012.
(498) Sikora, B.; Eoff, R. L.; Matson, S. W.; Raney, K. D. DNA
Unwinding by Escherichia coli DNA Helicase I (TraI) Provides
Evidence for a Processive Monomeric Molecular Motor. J. Biol. Chem.
2006, 281, 36110−36116.
(499) Guo, H.; Salahub, D. R. Cooperative Hydrogen Bonding and
Enzyme Catalysis. Angew. Chem., Int. Ed. 1998, 37, 2985−2990.
(500) Liu, J. Q.; Wulff, G. Functional Mimicry of the Active Site of
Carboxypeptidase A by a Molecular Imprinting Strategy: Cooperativity
of an Amidinium and a Copper Ion in a Transition-State Imprinted
Cavity Giving Rise to High Catalytic Activity. J. Am. Chem. Soc. 2004,
126, 7452−7453.
(501) van Oijen, A. M. Cutting the Forest to See a Single Tree? Nat.
Chem. Biol. 2008, 4, 440−443.
(502) Bonivento, D.; Milczek, E. M.; McDonald, G. R.; Binda, C.; Holt,
A.; Edmondson, D. E.; Mattevi, A. Potentiation of Ligand Binding
through Cooperative Effects in Monoamine Oxidase B. J. Biol. Chem.
2010, 285, 36849−36856.
(503) Hammes, G. G.; Benkovic, S. J.; Hammes-Schiffer, S. Flexibility,
Diversity, and Cooperativity: Pillars of Enzyme Catalysis. Biochemistry
2011, 50, 10422−10430.
(504) Denisov, I. G.; Frank, D. J.; Sligar, S. G. Cooperative Properties
of Cytochromes P450. Pharmacol. Ther. 2009, 124, 151−167.
2818
Review
(505) Ueng, Y. F.; Kuwabara, T.; Chun, Y. J.; Guengerich, F. P.
Cooperativity in Oxidations Catalyzed by Cytochrome P450 3A4.
Biochemistry 1997, 36, 370−381.
(506) Harlow, G. R.; Halpert, J. R. Analysis of Human Cytochrome
P450 3A4 Cooperativity: Construction and Characterization of a Site-
Directed Mutant that Displays Hyperbolic Steroid Hydroxylation
Kinetics. Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 6636−6641.
(507) Bren, U.; Oostenbrink, C. Cytochrome P450 3A4 Inhibition by
Ketoconazole: Tackling the Problem of Ligand Cooperativity Using
Molecular Dynamics Simulations and Free-Energy Calculations. J.
Chem. Inf. Model. 2012, 52, 1573−1582.
(508) Qian, H. Thermodynamic and Kinetic Analysis of Sensitivity
Amplification in Biological Signal Transduction. Biophys. Chem. 2003,
105, 585−593.
(509) Qian, H.; Cooper, J. A. Temporal Cooperativity and Sensitivity
Amplification in Biological Signal Transduction. Biochemistry 2008, 47,
2211−2220.
(510) DeChancie, J.; Houk, K. N. The Origins of Femtomolar Protein-
Ligand Binding: Hydrogen-Bond Cooperativity and Desolvation
Energetics in the Biotin-(Strept)Avidin Binding Site. J. Am. Chem. Soc.
2007, 129, 5419−5429.
(511) Van Roey, K.; Orchard, S.; Kerrien, S.; Dumousseau, M.; Ricard-
Blum, S.; Hermjakob, H.; Gibson, T. J. Capturing Cooperative
Interactions with the PSI-MI Format. Database 2013, 2013, bat066.
(512) Clausen, T.; Kaiser, M.; Huber, R.; Ehrmann, M. HTRA
Proteases: Regulated Proteolysis in Protein Quality Control. Nat. Rev.
Mol. Cell Biol. 2011, 12, 152−162.
(513) Di Cera, E. Serine Proteases. IUBMB Life 2009, 61, 510−515.
(514) Gohara, D. W.; Di Cera, E. Allostery in Trypsin-like Proteases
Suggests New Therapeutic Strategies. Trends Biotechnol. 2011, 29, 577−
585.
(515) Warshel, A.; Sharma, P. K.; Kato, M.; Xiang, Y.; Liu, H.; Olsson,
M. H. M. Electrostatic Basis for Enzyme Catalysis. Chem. Rev. 2006, 106,
3210−3235.
(516) Sohn, J.; Grant, R. A.; Sauer, R. T. Allostery is an Intrinsic
Property of the Protease Domain of DegS. J. Biol. Chem. 2010, 285,
34039−34047.
(517) Polgár, L. The Catalytic Triad of Serine Peptidases. Cell. Mol. Life
Sci. 2005, 62, 2161−2172.
(518) Lee, G. M.; Shahian, T.; Baharuddin, A.; Gable, J. E.; Craik, C. S.
Enzyme Inhibition by Allosteric Capture of an Inactive Conformation. J.
Mol. Biol. 2011, 411, 999−1016.
(519) Chen, H.; Zhou, X.; Ou-Yang, Z.-C. Classification of Amino
Acids Based On Statistical Results of Known Structures and
Cooperativity of Protein Folding. Phys. Rev. E Stat. Nonlin. Soft Matter
Phys. 2002, 65, 061907.
(520) Koch, O.; Bocola, M.; Klebe, G. Cooperative Effects in
Hydrogen-Bonding of Protein Secondary Structure Elements: A
Systematic Analysis of Crystal Data Using Secbase. Proteins: Struct.,
Funct., Genet. 2005, 61, 310−317.
(521) Cho, Y. R.; Maguire, A. J.; Try, A. C.; Westwell, M. S.; Groves, P.;
Williams, D. H. Cooperativity and AntiCooperativity between Ligand
Binding and the Dimerization of Ristocetin A: Asymmetry of a
Homodimer Complex and Implications for Signal Transduction. Chem.
Biol. 1996, 3, 207−215.
(522) Williams, D. H.; Stephens, E.; O’Brien, D. P.; Zhou, M.
Understanding Noncovalent Interactions: Ligand Binding Energy and
Catalytic Efficiency from Ligand-Induced Reductions in Motion within
Receptors and Enzymes. Angew. Chem., Int. Ed. 2004, 43, 6596−6616.
(523) Williams, D. H.; Maguire, A. J.; Tsuzuki, W.; Westwell, M. S. An
Analysis of the Origins of a Cooperative Binding Energy of
Dimerization. Science 1998, 280, 711−714.
(524) Williams, D. H.; Davies, N. L.; Zerella, R.; Bardsley, B.
Noncovalent Interactions: Defining Cooperativity. Ligand Binding
Aided by Reduced Dynamic Behavior of Receptors. Binding of Bacterial
Cell Wall Analogues to Ristocetin. A. J. Am. Chem. Soc. 2004, 126,
2042−2049.
(525) Baum, B.; Muley, L.; Smolinski, M.; Heine, A.; Hangauer, D.;
Klebe, G. Non-Additivity of Functional Group Contributions in
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
Protein−Ligand Binding: A Comprehensive Study by Crystallography
and Isothermal Titration Calorimetry. J. Mol. Biol. 2010, 397, 1042−
1054.
(526) Muley, L.; Baum, B.; Smolinski, M.; Freindorf, M.; Heine, A.;
Klebe, G.; Hangauer, D. G. Enhancement of Hydrophobic Interactions
and Hydrogen Bond Strength by Cooperativity: Synthesis, Modeling,
and Molecular Dynamics Simulations of a Congeneric Series of
Thrombin Inhibitors. J. Med. Chem. 2010, 53, 2126−2135.
(527) Nasief, N. N.; Tan, H.; Kong, J.; Hangauer, D. Water Mediated
Ligand Functional Group Cooperativity: The Contribution of a Methyl
Group to Binding Affinity is Enhanced by a COO− Group Through
Changes in the Structure and Thermodynamics of the Hydration Waters
of Ligand−Thermolysin Complexes. J. Med. Chem. 2012, 55, 8283−
8302.
(528) Biela, A.; Betz, M.; Heine, A.; Klebe, G. Water Makes the
Difference: Rearrangement of Water Solvation Layer Triggers Non-
additivity of Functional Group Contributions in Protein−Ligand
Binding. ChemMedChem 2012, 7, 1423−1434.
(529) Kuhn, B.; Fuchs, J. E.; Reutlinger, M.; Stahl, M.; Taylor, N. R.
Rationalizing Tight Ligand Binding through Cooperative Interaction
Networks. J. Chem. Inf. Model. 2011, 51, 3180−3198.
(530) Houk, K. N.; Leach, A. G.; Kim, S. P.; Zhang, X. Binding
Affinities of Host−Guest, Protein−Ligand, and Protein−Transition-
State Complexes. Angew. Chem., Int. Ed. 2003, 42, 4872−4897.
(531) Said, A. M.; Hangauer, D. G. Binding Cooperativity Between a
Ligand Carbonyl Group and a Hydrophobic Side Chain Can be
Enhanced by Additional H-Bonds in a Distance Dependent Manner: A
Case Study with Thrombin Inhibitors. Eur. J. Med. Chem. 2015, 96,
405−424.
(532) Nasief, N. N.; Hangauer, D. Additivity or Cooperativity: Which
Model Can Predict the Influence of Simultaneous Incorporation of Two
or More Functionalities in a Ligand Molecule? Eur. J. Med. Chem. 2015,
90, 897−915.
(533) Janardhan, S.; Srivani, P.; Sastry, G. N. Choline Kinase: An
Important Target for Cancer. Curr. Med. Chem. 2006, 13, 1169−1189.
(534) Janardhan, S.; Srivani, P.; Sastry, G. N. 2D and 3D Quantitative
Structure-Activity Relationship Studies on a Series of bis-Pyridinium
Compounds as Choline Kinase Inhibitors. QSAR Comb. Sci. 2006, 25,
860−872.
(535) Srivani, P.; Sastry, G. N. Potential Choline Kinase Inhibitors: A
Molecular Modeling Study of bis-Quinolinium Compounds. J. Mol.
Graphics Modell. 2009, 27, 676−688.
(536) Kulkarni, R.; Achaiah, G.; Sastry, G. N. Novel Targets for Anti-
Inflammatory and Anti-Arthritic Agents. Curr. Pharm. Des. 2006, 12,
2437−2454.
(537) Badrinarayan, P.; Sastry, G. N. Specificity Rendering ‘Hot-Spots’
for Aurora Kinase Inhibitor Design: The Role of Non-Covalent
Interactions and Conformational Transitions. PLoS One 2014, 9,
e113773.
(538) Badrinarayan, P.; Sastry, G. N. Sequence, Analysis of p38 MAP
Kinase: Exploiting DFG-Out Conformation as a Strategy to Design New
Type II leads. J. Chem. Inf. Model. 2011, 51, 115−129.
(539) Badrinarayan, P.; Sastry, G. N. Virtual Screening Filters for the
Design of Type II p38 MAP Kinase Inhibitors: A Fragment Based
Library Generation Approach. J. Mol. Graphics Modell. 2012, 34, 89−
100.
(540) Badrinarayan, P.; Sastry, G. N. Rational Approaches towards
Lead Optimization of Kinase Inhibitors: The Issue of Specificity. Curr.
Pharm. Des. 2013, 19, 4714−4738.
(541) Choudhury, C.; Priyakumar, U. D.; Sastry, G. N. Dynamics
Based Pharmacophore Models for Screening Potential Inhibitors of
Mycobacterial Cyclopropane Synthase. J. Chem. Inf. Model. 2015, 55,
848−860.
(542) Reddy, A. S.; Pati, S. P.; Kumar, P. P.; Pradeep, H. N.; Sastry, G.
N. Virtual Screening in Drug Discovery − A Computational Perspective.
Curr. Protein Pept. Sci. 2007, 8, 329−351.
(543) Srivastava, H. K.; Sastry, G. N. A Molecular Dynamics
Investigation on a Series of HIV Protease Inhibitors: Assessing the
2819
Review
Performance of MM-PBSA and MM-GBSA Approaches. J. Chem. Inf.
Model. 2012, 52, 3088−3098.
(544) Srivastava, H. K.; Chourasia, M.; Kumar, D.; Sastry, G. N.
Comparison of Computational Methods to Model DNA Minor Groove
Binders. J. Chem. Inf. Model. 2011, 51, 558−571.
(545) Bindu, P. H.; Sastry, G. M.; Sastry, G. N. Characterization of
Calcium and Magnesium Binding Domains of Human5-Lipoxygenase.
Biochem. Biophys. Res. Commun. 2004, 320, 461−467.
(546) Chourasia, M.; Sastry, G. M.; Sastry, G. N. Proton Binding Sites
and Conformational Analysis of H+K+-ATPase. Biochem. Biophys. Res.
Commun. 2005, 336, 961−966.
(547) Levinthal, C. Are there Pathways for Protein Folding? J. Chim.
Phys. 1968, 65, 44−45.
(548) Karplus, M.; Weaver, D. L. Protein-Folding Dynamics. Nature
1976, 260, 404−406.
(549) Kim, P. S.; Baldwin, R. L. Specific Intermediates in the Folding
Reactions of Small Proteins and the Mechanism of Protein Folding.
Annu. Rev. Biochem. 1982, 51, 459−489.
(550) Bryngelson, J. D.; Onuchic, J. N.; Socci, N. D.; Wolynes, P. G.
Funnels, Pathways, and the Energy Landscape of Protein Folding: A
Synthesis. Proteins: Struct., Funct., Genet. 1995, 21, 167−195.
(551) Radford, S. E.; Dobson, C. M.; Evans, P. A. The Folding of Hen
Lysozyme Involves Partially Structured Intermediates and Multiple
Pathways. Nature 1992, 358, 302−307.
(552) Freire, E.; Murphy, K. P.; Sanchez-Ruiz, J. M.; Galisteo, M. L.;
Privalov, P. L. The Molecular Basis of Cooperativity in Protein Folding.
Thermodynamic Dissection of Interdomain Interactions in Phospho-
glycerate Kinase. Biochemistry 1992, 31, 250−256.
(553) Staniforth, R. A.; Burston, S. G.; Smith, C. J.; Jackson, G. S.;
Badcoe, I. G.; Atkinson, T.; Holbrook, J. J.; Clarke, A. R. The Energetics
and Cooperativity of Protein Folding: A Simple Experimental Analysis
based upon the Solvation of Internal Residues. Biochemistry 1993, 32,
3842−3851.
(554) Udgaonkar, J. B.; Baldwin, R. L. NMR Evidence for an Early
Framework Intermediate on the Folding Pathway of Ribonuclease A.
Nature 1988, 335, 694−699.
(555) Baker, D. A Surprising Simplicity to Protein Folding. Nature
2000, 405, 39−42.
(556) Kuwajima, K. The Molten Globule State as a Clue for
Understanding the Folding and Cooperativity of Globular-Protein
Structure. Proteins: Struct., Funct., Genet. 1989, 6, 87−103.
(557) Dill, K. A.; Fiebig, K. M.; Chan, H. S. Cooperativity in Protein-
Folding Kinetics. Proc. Natl. Acad. Sci. U. S. A. 1993, 90, 1942−1946.
(558) Ghosh, K.; Dill, K. A. Theory for Protein Folding Cooperativity:
Helix Bundles. J. Am. Chem. Soc. 2009, 131, 2306−2312.
(559) Chan, H. S. Modeling Protein Density of States: Additive
Hydrophobic Effects Are Insufficient for Calorimetric Two-State
Cooperativity. Proteins: Struct., Funct., Genet. 2000, 40, 543−571.
(560) Kaya, H.; Chan, H. S. Towards a Consistent Modeling of Protein
Thermodynamic and Kinetic Cooperativity: How Applicable is the
Transition State Picture to Folding and Unfolding? J. Mol. Biol. 2002,
315, 899−909.
(561) Badasyan, A.; Liu, Z.; Chan, H. S. Interplaying Roles of Native
Topology and Chain Length in Marginally Cooperative and Non-
cooperative Folding of Small Protein Fragments. Int. J. Quantum Chem.
2009, 109, 3482−3499.
(562) Scalley-Kim, M.; Baker, D. Characterization of the Folding
Energy Landscapes of Computer Generated Proteins Suggests High
Folding Free Energy Barriers and Cooperativity may be Consequences
of Natural Selection. J. Mol. Biol. 2004, 338, 573−583.
(563) Watters, A. L.; Deka, P.; Corrent, C.; Callender, D.; Varani, G.;
Sosnick, T.; Baker, D. The Highly Cooperative Folding of Small
Naturally Occurring Proteins is likely the Result of Natural Selection.
Cell 2007, 128, 613−624.
(564) Plaxco, K. W.; Simons, K. T.; Baker, D. Contact Order,
Transition State Placement and the Refolding Rates of Single Domain
Proteins. J. Mol. Biol. 1998, 277, 985−994.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(565) Jewett, A. I.; Pande, V. S.; Plaxco, K. W. Cooperativity, Smooth
Energy Landscapes and the Origins of Topology-Dependent Protein
Folding Rates. J. Mol. Biol. 2003, 326, 247−253.
(566) Faísca, P. F. N.; Plaxco, K. W. Cooperativity and the Origins of
Rapid, Single-Exponential Kinetics in Protein Folding. Protein Sci. 2006,
15, 1608−1618.
(567) Zhou, Y.; Linhananta, A. Thermodynamics of an All-Atom Off-
Lattice Model of the Fragment B of Staphylococcal Protein A:
Implication for the Origin of the Cooperativity of Protein Folding. J.
Phys. Chem. B 2002, 106, 1481−1485.
(568) Klimov, D. K.; Thirumalai, D. Cooperativity in Protein Folding:
From Lattice Models with Sidechains to Real Proteins. Folding Des.
1998, 3, 127−139.
(569) Kouza, M.; Li, M. S.; O’Brien, E. P., Jr.; Hu, C.; Thirumalai, D.
Effect of Finite Size on Cooperativity and Rates of Protein Folding. J.
Phys. Chem. A 2006, 110, 671−676.
(570) Yang, X.; Kathuria, S. V.; Vadrevu, R.; Matthews, C. R. PLoS One
2009, 4, e7179−9.
(571) Canet, D.; Last, A. M.; Tito, P.; Sunde, M.; Spencer, A.; Archer,
D. B.; Redfield, C.; Robinson, C. V.; Dobson, C. M. Local Cooperativity
in the Unfolding of an Amyloidogenic Variant of Human Lysozyme.
Nat. Struct. Biol. 2002, 9, 308−315.
(572) Batey, S.; Clarke, J. Apparent Cooperativity in the Folding of
Multidomain Proteins Depends on the Relative Rates of Folding of the
Constituent Domains. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 18113−
18118.
(573) Shank, E. A.; Cecconi, C.; Dill, J. W.; Marqusee, S.; Bustamante,
C. The Folding Cooperativity of a Protein is Controlled by its Chain
Topology. Nature 2010, 465, 637−640.
(574) Schenck, H. L.; Gellman, S. H. Use of a Designed Triple-
Stranded Antiparallel β-Sheet to Probe β-Sheet Cooperativity in
Aqueous Solution. J. Am. Chem. Soc. 1998, 120, 4869−4870.
(575) Searle, M. S.; Ciani, B. Design of β-Sheet Systems for
Understanding the Thermodynamics and Kinetics of Protein Folding.
Curr. Opin. Struct. Biol. 2004, 14, 458−464.
(576) Xu, Y.; Bunagan, M. R.; Tang, J.; Gai, F. Probing the Kinetic
Cooperativity of β-Sheet Folding Perpendicular to the Strand Direction.
Biochemistry 2008, 47, 2064.
(577) Roe, D. R.; Hornak, V.; Simmerling, C. Folding Cooperativity in
a Three-Stranded β-Sheet Model. J. Mol. Biol. 2005, 352, 370−381.
(578) Hills, R. D., Jr.; Brooks, C. L., III Hydrophobic Cooperativity as a
Mechanism for Amyloid Nucleation. J. Mol. Biol. 2007, 368, 894−901.
(579) Ralston, C. Y.; He, Q.; Brenowitz, M.; Chance, M. R. Stability
and Cooperativity of Individual Tertiary Contacts in RNA Revealed
through Chemical Denaturation. Nat. Struct. Biol. 2000, 7, 371−374.
(580) Siegfried, N. A.; Metzger, S. L.; Bevilacqua, P. C. Folding
Cooperativity in RNA and DNA is Dependent on Position in the Helix.
Biochemistry 2007, 46, 172−181.
(581) Feng, J.; Walter, N. G.; Brooks, C. L. Cooperative and
Directional Folding of the preQ1 Riboswitch Aptamer Domain. J. Am.
Chem. Soc. 2011, 133, 4196−4199.
(582) Zuo, G.; Wang, J.; Wang, W. Folding with Downhill Behavior
and Low Cooperativity of Proteins. Proteins: Struct., Funct., Genet. 2006,
63, 165−173.
(583) Zhou, Z.; Bai, Y. Structural Biology: Analysis of Protein-Folding
Cooperativity. Nature 2007, 445, E16−E17.
(584) Sadqi, M.; Fushman, D.; Muñoz, V. Atom-by-Atom Analysis of
Global Downhill Protein Folding. Nature 2006, 442, 317−321.
(585) Ferguson, N.; Sharpe, T. D.; Johnson, C. M.; Schartau, P. J.;
Fersht, A. R. Structural Biology: Analysis of ’Downhill’ Protein Folding.
Nature 2007, 445, E14−E15.
(586) Li, Y.; Ji, C.; Xu, W.; Zhang, J. Z. H. Dynamical Stability and
Assembly Cooperativity of β-Sheet Amyloid Oligomers − Effect of
Polarization. J. Phys. Chem. B 2012, 116, 13368−13373.
(587) Diehl, M. R.; Zhang, K.; Lee, H. J.; Tirrell, D. A. Engineering
Cooperativity in Biomotor-Protein Assemblies. Science 2006, 311,
1468−1471.
2820
Review
(588) Orlova, A.; Prochniewicz, E.; Egelman, E. H. Structural
Dynamics of F-Actin: II. Cooperativity in Structural Transitions. J.
Mol. Biol. 1995, 245, 598−607.
(589) Kolinski, A.; Galazka, W.; Skolnick, J. On the Origin of the
Cooperativity of Protein Folding: Implications from Model Simulations.
Proteins: Struct., Funct., Genet. 1996, 26, 271−287.
(590) Luo, Y.; Kay, M. S.; Baldwin, R. L. Cooperativity of Folding of
the Apomyoglobin pH4 Intermediate Studied by Glycine and Proline
Mutations. Nat. Struct. Biol. 1997, 4, 925−930.
(591) Fernandez, A.; Colubri, A.; Berry, R. S. Three-body Correlations
in Protein Folding: The Origin of Cooperativity. Phys. A 2002, 307,
235−259.
(592) Keskin, O.; Ma, B.; Rogale, K.; Gunasekaran, K.; Nussinov, R.
Protein−Protein Interactions: Organization, Cooperativity and Map-
ping in a Bottom-Up Systems Biology Approach. Phys. Biol. 2005, 2,
S24−S35.
(593) Kloss, E.; Courtemanche, N.; Barrick, D. Repeat-Protein
Folding: New Insights into Origins of Cooperativity, Stability, and
Topology. Arch. Biochem. Biophys. 2008, 469, 83−99.
(594) Yang, L.; Song, G.; Jernigan, R. L. Protein Elastic Network
Models and the Ranges of Cooperativity. Proc. Natl. Acad. Sci. U. S. A.
2009, 106, 12347−12352.
(595) Sengupta, D.; Kundu, S. Role of Long- and Short-Range
Hydrophobic, Hydrophilic and Charged Residues Contact Network in
Protein’s Structural Organization. BMC Bioinf. 2012, 13, 142−14.
(596) Gruszka, D. T.; Whelan, F.; Farrance, O. E.; Fung, H. K.; Paci, E.;
Jeffries, C. M.; Svergun, D. I.; Baldock, C.; Baumann, C. G.; Brockwell,
D. J.; Potts, J. R.; Clarke, J. Cooperative Folding of Intrinsically
Disordered Domains Drives Assembly of a Strong Elongated Protein.
Nat. Commun. 2015, 6, 7271−7279.
(597) Malhotra, P.; Udgaonkar, J. B. Tuning Cooperativity on the Free
Energy Landscape of Protein Folding. Biochemistry 2015, 54, 3431−
3441.
(598) Schüle, R.; Muller, M.; Otsuka-Murakami, H.; Renkawitz, R.
Cooperativity of the Glucocorticoid Receptor and the CACCC-Box
Binding Factor. Nature 1988, 332, 87−90.
(599) Ogata, K.; Sato, K.; Tahirov, T. H. Eukaryotic Transcriptional
Regulatory Complexes: Cooperativity from Near and Afar. Curr. Opin.
Struct. Biol. 2003, 13, 40−48.
(600) Dodd, I. B.; Shearwin, K. E.; Perkins, A. J.; Burr, T.; Hochschild,
A.; Egan, J. B. Cooperativity in Long-Range Gene Regulation by the λ CI
Repressor. Genes Dev. 2004, 18, 344−354.
(601) Dandanell, G.; Valentin-Hansen, P.; Larsen, J. E.; Hammer, K.
Long-Range Cooperativity between Gene Regulatory Sequences in a
Prokaryote. Nature 1987, 325, 823−826.
(602) Banerjee, N.; Zhang, M. Q. Identifying Cooperativity among
Transcription Factors Controlling the Cell Cycle in Yeast. Nucleic Acids
Res. 2003, 31, 7024−7031.
(603) Dehner, A.; Klein, C.; Hansen, S.; Müller, L.; Buchner, J.;
Schwaiger, M.; Kessler, H. Cooperative Binding of p53 to DNA:
Regulation by Protein−Protein Interactions through a Double Salt
Bridge. Angew. Chem., Int. Ed. 2005, 44, 5247−5251.
(604) Krell, T.; Terán, W.; Mayorga, O. L.; Rivas, G.; Jiménez, M.;
Daniels, C.; Molina-Henares, A. J.; Martínez-Bueno, M.; Gallegos, M.
T.; Ramos, J. L. Optimization of the Palindromic Order of the TtgR
Operator Enhances Binding Cooperativity. J. Mol. Biol. 2007, 369,
1188−1199.
(605) King, J. C.; Xu, J.; Wongvipat, J.; Hieronymus, H.; Carver, B. S.;
Leung, D. H.; Taylor, B. S.; Sander, C.; Cardiff, R. D.; Couto, S. S.;
Gerald, W. L.; Sawyers, C. L. Cooperativity of TMPRSS2-ERG with PI3-
Kinase Pathway Activation in Prostate Oncogenesis. Nat. Genet. 2009,
41, 524−526.
(606) Mirny, L. A. Nucleosome-Mediated Cooperativity between
Transcription Factors. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 22534−
22539.
(607) Mekler, V.; Severinov, K. Cooperativity and Interaction Energy
Threshold Effects in Recognition of the − 10 Promoter Element by
Bacterial RNA Polymerase. Nucleic Acids Res. 2013, 41, 7276−7285.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(608) Kerppola, T. K.; Curran, T. Fos-Jun Heterodimers and Jun
Homodimers Bend DNA in Opposite Orientations: Implications for
Transcription Factor Cooperativity. Cell 1991, 66, 317−326.
(609) Mel’nikov, S. M.; Sergeyev, V. G.; Yoshikawa, K.; Takahashi, H.;
Hatta, I. Cooperativity or Phase Transition? Unfolding Transition of
DNA Cationic Surfactant Complex. J. Chem. Phys. 1997, 107, 6917−
6924.
(610) Becaud, J.; Pompizi, I.; Leumann, C. J. Propagation of Melting
Cooperativity along the Phosphodiester Backbone of DNA. J. Am.
Chem. Soc. 2003, 125, 15338−15342.
(611) Escudero, D.; Estarellas, C.; Frontera, A.; Quiñonero, D.; Deyà,
P. M. Cooperativity Effects between Noncovalent Interactions: Are they
important for Z-DNA Stability? Chem. Phys. Lett. 2010, 485, 221−225.
(612) Yurenko, Y. P.; Novotný, J.; Sklenár,̌ V.; Marek, R. Exploring
Noncovalent Interactions in Guanine- and Xanthine-Based Model DNA
Quadruplex Structures: A Comprehensive Quantum Chemical
Approach. Phys. Chem. Chem. Phys. 2014, 16, 2072−2084.
(613) Gong, B. Molecular Duplexes with Encoded Sequences and
Stabilities. Acc. Chem. Res. 2012, 45, 2077−2087.
(614) Arbona, J.; Aimé, J.; Elezgaray, J. Cooperativity in the Annealing
of DNA Origamis. J. Chem. Phys. 2013, 138, 015105−10.
(615) Norregaard, K.; Andersson, M.; Sneppen, K.; Nielsen, P. E.;
Brown, S.; Oddershede, L. B. DNA Supercoiling Enhances Coopera-
tivity and Efficiency of an Epigenetic Switch. Proc. Natl. Acad. Sci. U. S. A.
2013, 110, 17386−17391.
(616) Sattin, B. D.; Zhao, W.; Travers, K.; Chu, S.; Herschlag, D. Direct
Measurement of Tertiary Contact Cooperativity in RNA Folding. J. Am.
Chem. Soc. 2008, 130, 6085−6087.
(617) Kwon, M.; Strobel, S. A. Chemical Basis of Glycine Riboswitch
Cooperativity. RNA 2007, 14, 25−34.
(618) Overgaard, M.; Borch, J.; Jørgensen, M. G.; Gerdes, K.
Messenger RNA Interferase RelE Controls relBE Transcription by
Conditional Cooperativity. Mol. Microbiol. 2008, 69, 841−857.
(619) Said, H.; Schüller, V. J.; Eber, F. J.; Wege, C.; Liedl, T.; Richert,
C. M1.3 − A Small Scaffold for DNA Origami. Nanoscale 2013, 5, 284−
290.
(620) Ares, S.; Voulgarakis, N. K.; Rasmussen, K. Ø.; Bishop, A. R.
Bubble Nucleation and Cooperativity in DNA Melting. Phys. Rev. Lett.
2005, 94, No. 035504.
(621) Bolognesi, M.; Boffi, A.; Coletta, M.; Mozzarelli, A.; Pesce, A.;
Tarricone, C.; Ascenzi, P. Anticooperative Ligand Binding Properties of
Recombinant Ferric Vitreoscilla Homodimeric Hemoglobin: A
Thermodynamic, Kinetic and X-ray Crystallographic Study. J. Mol.
Biol. 1999, 291, 637−650.
(622) Iqbalsyah, T. M.; Doig, A. J. Anticooperativity in a Glu−Lys−
Glu Salt Bridge Triplet in an Isolated α-Helical Peptide. Biochemistry
2005, 44, 10449−10456.
(623) Piazza, F.; De Los Rios, P.; Fanelli, D.; Bongini, L.; Skoglund, U.
Anticooperativity in Diffusion-Controlled Reactions with Pairs of
Partially Absorbing Domains: A Model for the Antigen-Antibody
Encounter. Eur. Biophys. J. 2005, 34, 899−911.
(624) Li, X.; Liang, J. Geometric Cooperativity and Anticooperativity
of Three-Body Interactions in Native Proteins. Proteins: Struct., Funct.,
Genet. 2005, 60, 46−65.
(625) Czaplewski, C.; Liwo, A.; Ripoll, D. R.; Scheraga, H. A.
Molecular Origin of Anticooperativity in Hydrophobic Association. J.
Phys. Chem. B 2005, 109, 8108−8119.
(626) Shimizu, S.; Moghaddam, M. S.; Chan, H. S. Comment on
“Molecular Origin of Anticooperativity in Hydrophobic Association. J.
Phys. Chem. B 2005, 109, 21220−21221.
(627) Kudrev, A. G. Calculation of the Cooperativity and
Anticooperativity Parameters of the Interaction of a Ligand with an
Infinite Homogeneous Polymer. J. Anal. Chem. 2001, 56, 232−237.
(628) Cysewski, P. Non-Additive Interactions of Nucleobases in
Model Dinucleotide Steps Occurring in B-DNA Crystals. J. Mol. Model.
2010, 16, 1721−1729.
(629) Szczięśniak, M. M.; Ratajczak, H. Nonadditivity of the SCF
Interaction Energy in the (LiH)3 Complex. Int. J. Quantum Chem. 1980,
17, 1069−1074.
2821
Review
(630) Antony, J.; Grimme, S. Structures and Interaction Energies of
Stacked Graphene−Nucleobase Complexes. Phys. Chem. Chem. Phys.
2008, 10, 2722−2729.
(631) Levitzki, A.; Koshland, D. E., Jr. Negative Cooperativity in
Regulatory Enzymes. Proc. Natl. Acad. Sci. U. S. A. 1969, 62, 1121−1128.
(632) DeMeyts, P.; Bainco, A. R.; Roth, J. Site-Site Interactions among
Insulin Receptors. J. Biol. Chem. 1976, 251, 1877−1888.
(633) Koshland, D. E., Jr. The Structural Basis of Negative
Cooperativity: Receptors and Enzymes. Curr. Opin. Struct. Biol. 1996,
6, 757−761.
(634) Flatmark, T.; Almås, B.; Knappskog, P. M.; Berge, S. V.; Svebak,
R. M.; Chehin, R.; Muga, A.; Martínez, A. Tyrosine Hydroxylase Binds
Tetrahydrobiopterin Cofactor with Negative Cooperativity, as Shown
by Kinetic Analyses and Surface Plasmon Resonance Detection. Eur. J.
Biochem. 1999, 262, 840−849.
(635) Stevens, S. Y.; Sanker, S.; Kent, C.; Zuiderweg, E. R. Delineation
of the Allosteric Mechanism of a Cytidylyltransferase Exhibiting
Negative Cooperativity. Nat. Struct. Biol. 2001, 8, 947−952.
(636) Walter, E. D.; Chattopadhyay, M.; Millhauser, G. L. The Affinity
of Copper Binding to the Prion Protein Octarepeat Domain: Evidence
for Negative Cooperativity. Biochemistry 2006, 45, 13083−13092.
(637) Aramaki, H.; Kabata, H.; Takeda, S.; Itou, H.; Nakayama, H.;
Shimamoto, N. Formation of Repressor-Inducer-Operator Ternary
Complex: Negative Cooperativity of D-Camphor Binding to CamR.
Genes Cells. 2011, 16, 1200−1207.
(638) Wang, C.; Wang, Z.; Zhang, X. Amphiphilic Building Blocks for
Self-Assembly: From Amphiphiles to Supra-Amphiphiles. Acc. Chem.
Res. 2012, 45, 608−618.
(639) Mali, K. S.; Lava, K.; Binnemans, K.; De Feyter, S. Hydrogen
Bonding Versus van der Waals Interactions: Competitive Influence of
Noncovalent Interactions on 2D Self-Assembly at the Liquid−Solid
Interface. Chem. - Eur. J. 2010, 16, 14447−14458.
(640) Hoeben, F. J. M.; Jonkheijm, P.; Meijer, E. W.; Schenning, A. P.
H. J. About Supramolecular Assemblies of π-Conjugated Systems. Chem.
Rev. 2005, 105, 1491−1546.
(641) Jonkheijm, P.; van der Schoot, P.; Schenning, A. P. H. J.; Meijer,
E. W. Probing the Solvent-Assisted Nucleation Pathway in Chemical
Self-Assembly. Science 2006, 313, 80−83.
(642) Besenius, P.; Portale, G.; Bomans, P. H. H.; Janssen, H. M.;
Palmans, A. R. A.; Meijer, E. W. Controlling the Growth and Shape of
Chiral Supramolecular Polymers in Water. Proc. Natl. Acad. Sci. U. S. A.
2010, 107, 17888−17893.
(643) Markvoort, A. J.; ten Eikelder, H. M. M.; Hilbers, P. A. J.; de
Greef, T. F.A.; Meijer, E. W. Theoretical Models of Nonlinear Effects in
Two-Component Cooperative Supramolecular Copolymerizations.
Nat. Commun. 2011, 2, 509−9.
(644) García, F.; Korevaar, P. A.; Verlee, A.; Meijer, E. W.; Palmans, A.
R. A.; Sánchez, L. The Influence of π-Conjugated Moieties on the
Thermodynamics of Cooperatively Self-Assembling Tricarboxamides.
Chem. Commun. 2013, 49, 8674−8676.
(645) Smulders, M. M. J.; Schenning, A. P. H. J.; Meijer, E. W. Insight
into the Mechanisms of Cooperative Self-Assembly: The “Sergeants-
and-Soldiers” Principle of Chiral and Achiral C3-Symmetrical Discotic
Triamides. J. Am. Chem. Soc. 2008, 130, 606−611.
(646) van der Weegen, R.; Korevaar, P. A.; Voudouris, P.; Voets, I. K.;
de Greef, T. F.; Vekemans, J. A.; Meijer, E. W. Small Sized Perylene-
Bisimide Assemblies Controlled by Both Cooperative and AntiCooper-
ative Assembly Processes. Chem. Commun. 2013, 49, 5532−5534.
(647) Tian, Y.; Meijer, E. W.; Wang, F. Cooperative Self-Assembly of
Platinum(II) Acetylide Complexes. Chem. Commun. 2013, 49, 9197−
9199.
(648) Badjić, J. D.; Nelson, A.; Cantrill, S. J.; Turnbull, W. B.; Stoddart,
J. F. Multivalency and Cooperativity in Supramolecular Chemistry. Acc.
Chem. Res. 2005, 38, 723−732.
(649) Belowich, M. E.; Valente, C.; Smaldone, R. A.; Friedman, D. C.;
Thiel, J.; Cronin, L.; Stoddart, J. F. Positive Cooperativity in the
Template-Directed Synthesis of Monodisperse Macromolecules. J. Am.
Chem. Soc. 2012, 134, 5243−5261.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(650) Stone, M. T.; Heemstra, J. M.; Moore, J. S. The Chain-Length
Dependence Test. Acc. Chem. Res. 2006, 39, 11−20.
(651) Wackerly, J. W.; Moore, J. S. Cooperative Self-Assembly of
Oligo(m-phenyleneethynylenes) into Supramolecular Coordination
Polymers. Macromolecules 2006, 39, 7269−7276.
(652) Filot, I. A.W.; Palmans, A. R. A.; Hilbers, P. A. J.; van Santen, R.
A.; Pidko, E. A.; de Greef, T. F. A. Understanding Cooperativity in
Hydrogen-Bond-Induced Supramolecular Polymerization: A Density
Functional Theory Study. J. Phys. Chem. B 2010, 114, 13667−13674.
(653) Björk, J.; Stafström, S.; Hanke, F. Zipping Up: Cooperativity
Drives the Synthesis of Graphene Nanoribbons. J. Am. Chem. Soc. 2011,
133, 14884−14887.
(654) Riis-Johannessen, T.; Favera, N. D.; Todorova, T. K.; Huber, S.
M.; Gagliardi, L.; Piguet, C. Understanding, Controlling and
Programming Cooperativity in Self-Assembled Polynuclear Complexes
in Solution. Chem. - Eur. J. 2009, 15, 12702−12718.
(655) Roman, M.; Cannizzo, C.; Pinault, T.; Isare, B.; Andrioletti, B.;
van der Schoot, P.; Bouteiller, L. Supramolecular Balance: Using
Cooperativity To Amplify Weak Interactions. J. Am. Chem. Soc. 2010,
132, 16818−16824.
(656) Chung, M. K.; Lee, S. J.; Waters, M. L.; Gagné, M. R. Self-
Assembled Multi-Component Catenanes: The Effect of Multivalency
and Cooperativity on Structure and Stability. J. Am. Chem. Soc. 2012,
134, 11430−11443.
(657) Ercolani, G. Assessment of Cooperativity in Self-Assembly. J.
Am. Chem. Soc. 2003, 125, 16097−16103.
(658) Cao, D.; Wu, J. Theoretical Study of Cooperativity in
Multivalent Polymers for Colloidal Stabilization. Langmuir 2005, 21,
9786−9791.
(659) Kato, K.; Schneider, H. Cooperativity and Selectivity in
Chemomechanical Polyethylenimine Gels. Langmuir 2007, 23,
10741−10745.
(660) Prohens, R.; Portell, A.; Puigjaner, C.; Tomàs, S.; Fujii, K.;
Harris, K. D. M.; Alcobé, X.; Font-Bardia, M.; Barbas, R. Cooperativity
in Solid-State Squaramides. Cryst. Growth Des. 2011, 11, 3725−3730.
(661) Widanapathirana, L.; Zhao, Y. Aromatically Functionalized
Cyclic Tricholate Macrocycles: Aggregation, Transmembrane Pore
Formation, Flexibility, and Cooperativity. J. Org. Chem. 2012, 77, 4679−
4687.
(662) Rekharsky, M. V.; Yamamura, H.; Kawai, M.; Osaka, I.; Arakawa,
R.; Sato, A.; Ko, Y. H.; Selvapalam, N.; Kim, K.; Inoue, Y. Sequential
Formation of a Ternary Complex among Dihexylammonium,
Cucurbit[6]uril, and Cyclodextrin with Positive Cooperativity. Org.
Lett. 2006, 8, 815−818.
(663) Leclercq, L.; Noujeim, N.; Sanon, S. H.; Schmitzer, A. R. Study of
the Supramolecular Cooperativity in the Multirecognition Mechanism
of Cyclodextrins/Cucurbituril/Disubstituted Diimidazolium Bromides.
J. Phys. Chem. B 2008, 112, 14176−14184.
(664) Sato, H.; Tashiro, K.; Shinmori, H.; Osuka, A.; Murata, Y.;
Komatsu, K.; Aida, T. Positive Heterotropic Cooperativity for Selective
Guest Binding via Electronic Communications through a Fused Zinc
Porphyrin Array. J. Am. Chem. Soc. 2005, 127, 13086−13087.
(665) Ménand, M.; de Beaumais, S. A.; Chamoreau, L.; Derat, E.;
Blanchard, S.; Zhang, Y.; Bouteiller, L.; Sollogoub, M. Solid-State
Hierarchical Cyclodextrin-Based Supramolecular Polymer Constructed
by Primary, Secondary, and Tertiary Azido Interactions. Angew. Chem.,
Int. Ed. 2014, 53, 7238−7242.
(666) Howe, E. N. W.; Bhadbhade, M.; Thordarson, P. Cooperativity
and Complexity in the Binding of Anions and Cations to a Tetratopic
Ion-Pair Host. J. Am. Chem. Soc. 2014, 136, 7505−7516.
(667) Bejagam, K. K.; Fiorin, G.; Klein, M. L.; Balasubramanian, S.
Supramolecular Polymerization of Benzene-1, 3, 5-tricarboxamide: A
Molecular Dynamics Simulation Study. J. Phys. Chem. B 2014, 118,
5218−5228.
(668) Cheuk, K. K. L.; Lam, J. W. Y.; Lai, L. M.; Dong, Y.; Tang, B. Z.
Syntheses, Hydrogen-Bonding Interactions, Tunable Chain Helicities,
and Cooperative Supramolecular Associations and Dissociations of
Poly(Phenylacetylene)s Bearing l-Valine Pendants: Toward the
2822
Review
Development of Proteomimetic Polyenes. Macromolecules 2003, 36,
9752−9762.
(669) Lanigan, N.; Wang, X. Supramolecular Chemistry of Metal
Complexes in Solution. Chem. Commun. 2013, 49, 8133−8144.
(670) Prince, R. B.; Saven, J. G.; Wolynes, P. G.; Moore, J. S.
Cooperative Conformational Transitions in Phenylene Ethynylene
Oligomers: Chain-Length Dependence. J. Am. Chem. Soc. 1999, 121,
3114−3121.
(671) Stone, M. T.; Moore, J. S. Supramolecular Chelation Based on
Folding. J. Am. Chem. Soc. 2005, 127, 5928−5935.
(672) Camara-Campos, A.; Hunter, C. A.; Tomas, S. Cooperativity in
the Self-Assembly of Porphyrin Ladders. Proc. Natl. Acad. Sci. U. S. A.
2006, 103, 3034−3038.
(673) Ercolani, G.; Schiaffino, L. Allosteric, Chelate, and Interannular
Cooperativity: A Mise au Point. Angew. Chem., Int. Ed. 2011, 50, 1762−
1768.
(674) Mayoral, M. J.; Rest, C.; Stepanenko, V.; Schellheimer, J.;
Albuquerque, R. Q.; Fernández, G. Cooperative Supramolecular
Polymerization Driven by Metallophilic Pd···Pd Interactions. J. Am.
Chem. Soc. 2013, 135, 2148−2151.
(675) Fernández, G.; Stolte, M.; Stepanenko, V.; Würthner, F.
Cooperative Supramolecular Polymerization: Comparison of Different
Models Applied on the Self-Assembly of Bis(merocyanine) Dyes. Chem.
- Eur. J. 2013, 19, 206−217.
(676) Ke, C.; Smaldone, R. A.; Kikuchi, T.; Li, H.; Davis, A. P.;
Stoddart, J. F. Quantitative Emergence of Hetero[4]rotaxanes by
Template-Directed Click Chemistry. Angew. Chem., Int. Ed. 2013, 52,
381.
(677) Jena, H. S. Effect of Cooperative Noncovalent Interactions on
the Solid State Heterochiral Self-Assembly: The Concepts of Isotactic
and Syndiotactic Arrangements in Coordination Complex. Inorg. Chim.
Acta 2014, 410, 156−170.
(678) Aparicio, F.; Sánchez, L. Thermodynamics of the Helical,
Supramolecular Polymerization of Linear Self-Asembling Molecules:
Influence of Hydrogen Bonds and π Stacking. Chem. - Eur. J. 2013, 19,
10482−10486.
(679) Sun, H.; Navarro, C.; Hunter, C. A. Influence of Non-covalent
Preorganization on Supramolecular Effective Molarities. Org. Biomol.
Chem. 2015, 13, 4981−4992.
(680) Chan, A. K.; Wong, K. M.; Yam, V. W. Supramolecular Assembly
of Isocyanorhodium(I) Complexes: An Interplay of Rhodium(I)···
Rhodium(I) Interactions, Hydrophobic−Hydrophobic Interactions,
and Host−Guest Chemistry. J. Am. Chem. Soc. 2015, 137, 6920−6931.
(681) Hu, W.; Hu, W.; Liu, Y. A.; Li, J.; Jiang, B.; Wen, K. Negative
Cooperativity in the Binding of Imidazolium and Viologen Ions to a
Pillar[5]arene-Crown Ether Fused Host. Org. Lett. 2015, 17, 2940−
2943.
(682) Beyeh, N. K.; Ala-Korpi, A.; Pan, F.; Jo, H. H.; Anslyn, E. V.;
Rissanen, K. Cooperative Binding of Divalent Diamides by N-Alkyl
Ammonium Resorcinarene Chlorides. Chem. - Eur. J. 2015, 21, 9556−
9562.
(683) Mäkelä, T.; Kalenius, E.; Rissanen, K. Cooperatively Enhanced
Ion Pair Binding with a Hybrid Receptor. Inorg. Chem. 2015, 54, 9154−
9165.
(684) Yokoyama, S.; Hirose, T.; Matsuda, K. Effects of Alkyl Chain
Length and Hydrogen Bonds on the Cooperative Self-Assembly of 2-
Thienyl-Type Diarylethenes at a Liquid/Highly Oriented Pyrolytic
Graphite (HOPG) Interface. Chem. - Eur. J. 2015, 21, 13569−13576.
(685) Kulkarni, C.; Bejagam, K. K.; Senanayak, S. P.; Narayan, K. S.;
Balasubramanian, S.; George, S. J. Dipole-Moment-Driven Cooperative
Supramolecular Polymerization. J. Am. Chem. Soc. 2015, 137, 3924−
3932.
(686) Wang, X.; Miller, D. S.; Bukusoglu, E.; de Pablo, J. J.; Abbott, N.
L. Topological Defects in Liquid Crystals as Templates for Molecular
Self-assembly. Nat. Mater. 2015, 15, 106.
(687) Xu, J.; Chen, L.; Zhang, X. How to Make Weak Noncovalent
Interactions Stronger. Chem. - Eur. J. 2015, 21, 11938−11946.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
(688) Akhuli, B.; Ghosh, P. Selective Recognition and Extraction of
KBr via Cooperative Interactions with a Urea Functionalized Crown
Ether Dual-host. Chem. Commun. 2015, 51, 16514.
(689) Seth, S. K.; Sarkar, D.; Jana, A. D.; Kar, T. On the Possibility of
Tuning Molecular Edges To Direct Supramolecular Self-Assembly in
Coumarin Derivatives through Cooperative Weak Forces: Crystallo-
graphic and Hirshfeld Surface Analyses. Cryst. Growth Des. 2011, 11,
4837−4849.
(690) Hunter, C. A.; Misuraca, M. C.; Turega, S. M. Influence of H-
Bond Strength on Chelate Cooperativity. J. Am. Chem. Soc. 2011, 133,
20416−20425.
(691) Hogben, H. J.; Sprafke, J. K.; Hoffmann, M.; Pawlicki, M.;
Anderson, H. L. Stepwise Effective Molarities in Porphyrin Oligomer
Complexes: Preorganization Results in Exceptionally Strong Chelate
Cooperativity. J. Am. Chem. Soc. 2011, 133, 20962−20969.
(692) Jiang, W.; Nowosinski, K.; Löw, N. L.; Dzyuba, E. V.; Klautzsch,
F.; Schäfer, A.; Huuskonen, J.; Rissanen, K.; Schalley, C. A. Chelate
Cooperativity and Spacer Length Effects on the Assembly Thermody-
namics and Kinetics of Divalent Pseudorotaxanes. J. Am. Chem. Soc.
2012, 134, 1860−1868.
(693) Nowosinski, K.; von Krbek, L. K. S.; Traulsen, N. L.; Schalley, C.
A. Thermodynamic Analysis of Allosteric and Chelate Cooperativity in
Di- and Trivalent Ammonium/Crown-Ether Pseudorotaxanes. Org.
Lett. 2015, 17, 5076−5079.
(694) Traulsen, N. L.; Traulsen, C. H.-H.; Deutinger, P. M.; Müller, S.;
Schmidt, D.; Linder, I.; Schalley, C. A. Chelate Cooperativity Effects on
the Formation of Di- and Trivalent Pseudo[2]rotaxanes with
Diketopiperazine Threads and Tetralactam Wheels. Org. Biomol.
Chem. 2015, 13, 10881.
(695) Knowles, R. R.; Jacobsen, E. N. Attractive Noncovalent
Interactions in Asymmetric Catalysis: Links between Enzymes and
Small Molecule Catalysts. Proc. Natl. Acad. Sci. U. S. A. 2010, 107,
20678−20685.
(696) Xu, H.; Zuend, S. J.; Woll, M. G.; Tao, Y.; Jacobsen, E. N.
Asymmetric Cooperative Catalysis of Strong Brønsted Acid−Promoted
Reactions Using Chiral Ureas. Science 2010, 327, 986−990.
(697) Schreiner, P. R. Cooperativity Tames Reactive Catalysts. Science
2010, 327, 965−966.
(698) Schindler, C. S.; Jacobsen, E. N. A New Twist on Cooperative
Catalysis. Science 2013, 340, 1052−1053.
(699) Krautwald, S.; Sarlah, D.; Schafroth, M. A.; Carreira, E. M.
Enantio- and Diastereodivergent Dual Catalysis: α-Allylation of
Branched Aldehydes. Science 2013, 340, 1065−1068.
(700) Carrillo, R.; Feher-Voelger, A.; Martín, T. Enantioselective
Cooperativity between Intra-Receptor Interactions and Guest Binding:
Quantification of Reinforced Chiral Recognition. Angew. Chem., Int. Ed.
2011, 50, 10616−10620.
(701) Kanai, M.; Kato, N.; Ichikawa, E.; Shibasaki, M. Power of
Cooperativity: Lewis Acid−Lewis Base Bifunctional Asymmetric
Catalysis. Synlett 2005, 10, 1491−1508.
(702) Raup, D. E. A.; Cardinal-David, B.; Holte, D.; Scheidt, K. A.
Cooperative Catalysis by Carbenes and Lewis Acids in a Highly
Stereoselective Route to γ-Lactams. Nat. Chem. 2010, 2, 766−771.
(703) Patil, N. T. Merging Metal and N-Heterocyclic Carbene
Catalysis: On the Way to Discovering Enantioselective Organic
Transformations. Angew. Chem., Int. Ed. 2011, 50, 1759−1761.
(704) Potier, J.; Menuel, S.; Fournier, D.; Fourmentin, S.; Woisel, P.;
Monflier, E.; Hapiot, F. Cooperativity in Aqueous Organometallic
Catalysis: Contribution of Cyclodextrin-Substituted Polymers. ACS
Catal. 2012, 2, 1417−1420.
(705) Milsmann, C.; Turner, Z. R.; Semproni, S. P.; Chirik, P. J. Azo
NN Bond Cleavage with a Redox-Active Vanadium Compound
Involving Metal−Ligand Cooperativity. Angew. Chem., Int. Ed. 2012, 51,
5386−5390.
(706) Ho, J. H. H.; Choy, S. W. S.; Macgregor, S. A.; Messerle, B. A.
Cooperativity in Bimetallic Dihydroalkoxylation Catalysts Built on
Aromatic Scaffolds: Significant Rate Enhancements with a Rigid
Anthracene Scaffold. Organometallics 2011, 30, 5978−5984.
2823
Review
(707) Motta, A.; Fragalà, I. L.; Marks, T. J. Proximity and Cooperativity
Effects in Binuclear d0 Olefin Polymerization Catalysis. Theoretical
Analysis of Structure and Reaction Mechanism. J. Am. Chem. Soc. 2009,
131, 3974−3984.
(708) Mazzacano, T. J.; Mankad, N. P. Base Metal Catalysts for
Photochemical C−H Borylation that Utilize Metal−Metal Coopera-
tivity. J. Am. Chem. Soc. 2013, 135, 17258−17261.
(709) Mankad, N. P. Non-Precious Metal Catalysts for C−H
Borylation Enabled by Metal−Metal Cooperativity. Synlett 2014, 25,
1197−1201.
(710) Cantekin, S.; ten Eikelder, H. M. M.; Markvoort, A. J.; Veld, M.
A. J.; Korevaar, P. A.; Green, M. M.; Palmans, A. R. A.; Meijer, E. W.
Consequences of Cooperativity in Racemizing Supramolecular Systems.
Angew. Chem., Int. Ed. 2012, 51, 6426−6431.
(711) Fitz, B.; Andjelić, S.; Mijovic, J. Reorientational Dynamics and
Intermolecular Cooperativity of Reactive Polymers. 1. Model Epoxy−
Amine Systems. Macromolecules 1997, 30, 5227−5238.
(712) Xu, X.; Pooi, B.; Hirao, H.; Hong, S. H. CH−π and CF−π
Interactions Lead to Structural Changes of N-Heterocyclic Carbene
Palladium Complexes. Angew. Chem., Int. Ed. 2014, 53, 1283−1287.
(713) Broussard, M. E.; Juma, B.; Train, S. G.; Peng, W. J.; Laneman, S.
A.; Stanley, G. G. A Bimetallic Hydroformylation Catalyst: High
Regioselectivity and Reactivity through Homobimetallic Cooperativity.
Science 1993, 260, 1784−1788.
(714) Suss-Fink, G. Cooperativity in Rh2 Complexes: High Catalytic
Activity and High Regioselectivity in the Hydroformylation of Olefins.
Angew. Chem., Int. Ed. Engl. 1994, 33, 67−69.
(715) Chiang, K. P.; Bellows, S. M.; Brennessel, W. W.; Holland, P. L.
Multimetallic Cooperativity in Activation of Dinitrogen at Iron−
Potassium Sites. Chem. Sci. 2014, 5, 267−274.
(716) Al-Amin, M.; Roth, K. E.; Blum, S. A. Mechanistic Studies of
Gold and Palladium Cooperative Dual-Catalytic Cross-Coupling
Systems. ACS Catal. 2014, 4, 622−629.
(717) Cooper, O.; Camp, C.; Pécaut, J.; Kefalidis, C. E.; Maron, L.;
Gambarelli, S.; Mazzanti, M. Multimetallic Cooperativity in Uranium-
Mediated CO2 Activation. J. Am. Chem. Soc. 2014, 136, 6716−6723.
(718) Jindal, G.; Kisan, H. K.; Sunoj, R. B. Mechanistic Insights on
Cooperative Catalysis through Computational Quantum Chemical
Methods. ACS Catal. 2015, 5, 480−503.
(719) Raynal, M.; Ballester, P.; Vidal-Ferran, A.; van Leeuwen, P. W. N.
M. Supramolecular Catalysis. Part 1: Noncovalent Interactions as a Tool
for Building and Modifying Homogeneous Catalysts. Chem. Soc. Rev.
2014, 43, 1660−1733.
(720) Zhang, Z.; Lippert, K. M.; Hausmann, H.; Kotke, M.; Schreiner,
P. R. Cooperative Thiourea−Brønsted Acid Organocatalysis: Enantio-
selective Cyanosilylation of Aldehydes with TMSCN. J. Org. Chem.
2011, 76, 9764−9776.
(721) Kim, H. Y.; Oh, K. Highly Diastereo- and Enantioselective Aldol
Reaction of Methyl r-Isocyanoacetate: A Cooperative Catalysis
Approach. Org. Lett. 2011, 13, 1306−1309.
(722) Weil, T.; Kotke, M.; Kleiner, C. M.; Schreiner, P. R. Cooperative
Brønsted Acid-Type Organocatalysis: Alcoholysis of Styrene Oxides.
Org. Lett. 2008, 10, 1513−1516.
(723) Perdriau, S.; Zijlstra, D. S.; Heeres, H. J.; de Vries, J. G.; Otten, E.
A Metal−Ligand Cooperative Pathway for Intermolecular Oxa-Michael
Additions to Unsaturated Nitriles. Angew. Chem., Int. Ed. 2015, 54,
4236−4240.
(724) Gan, Q.; Ronson, T. K.; Vosburg, D. A.; Thoburn, J. D.;
Nitschke, J. R. Cooperative Loading and Release Behavior of a Metal-
Organic Receptor. J. Am. Chem. Soc. 2015, 137, 1770−1773.
(725) Schmidt, V. A.; Hoyt, J. M.; Margulieux, G. W.; Chirik, P. J.
Cobalt-Catalyzed [2π+2π] Cycloadditions of Alkenes: Scope, Mecha-
nism and Elucidation of Electronic Structure of Catalytic Intermediates.
J. Am. Chem. Soc. 2015, 137, 7903−7914.
(726) Li, H.; Marks, T. J. Nuclearity and Cooperativity Effects in
Binuclear Catalysts and Cocatalysts for Olefin Polymerization. Proc.
Natl. Acad. Sci. U. S. A. 2006, 103, 15295−15302.
(727) Rummelt, S. M.; Radkowski, K.; Roşca, D.; Fürstner, A.
Interligand Interactions Dictate the Regioselectivity of trans-Hydro-
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews
metalations and Related Reactions Catalyzed by [Cp*RuCl].Hydrogen
Bonding to a Chloride Ligand as a Steering Principle in Catalysis. J. Am.
Chem. Soc. 2015, 137, 5506−5519.
(728) Umadevi, D.; Panigrahi, S.; Sastry, G. N. Noncovalent
Interaction of Carbon Nanostructures. Acc. Chem. Res. 2014, 47,
2574−2581.
(729) Remya, K.; Suresh, C. H. Non-covalent Intermolecular Carbon−
Carbon Interactions in Polyynes. Phys. Chem. Chem. Phys. 2015, 17,
27035−27044.
(730) Umadevi, D.; Sastry, G. N. Quantum Mechanical Study of
Physisorption of Nucleobases on Carbon Materials: Graphene versus
Carbon Nanotubes. J. Phys. Chem. Lett. 2011, 2, 1572−1576.
(731) Umadevi, D.; Sastry, G. N. Impact of the Chirality and Curvature
of Carbon Nano Structure on their Interaction with Aromatics and
Aminoacids. ChemPhysChem 2013, 14, 2570−2578.
(732) Umadevi, D.; Sastry, G. N. Feasibility of Carbon Nanomaterials
as Gas Sensors: A Computational Investigation. Curr. Sci. 2014, 106,
1224−1234.
(733) Panigrahi, S.; Sastry, G. N. Reducing Polyaromatic Hydro-
carbons: The Capability and Capacity of Lithium. RSC Adv. 2014, 4,
14557−14563.
(734) Hussain, M. A.; Soujanya, Y.; Sastry, G. N. Computational
Design of Functionalized Imidazolate Linkers of Zeolitic Imidazolate
Frameworks for Enhanced CO2 Adsorption. J. Phys. Chem. C 2015, 119,
23607−23618.
(735) Umadevi, D.; Sastry, G. N. Graphane Versus Graphene: A
Computational Investigation of the Interaction of Nucleobases,
Aminoacids, Heterocycles, Small Molecules (CO2, H2O, NH3, CH4,
H2), Metal ions and Onium Ions. Phys. Chem. Chem. Phys. 2015, 17,
30260−30269.
(736) Hussain, M. A.; Vijay, D.; Sastry, G. N. Buckybowls as
Adsorbents for CO2, CH4, and C2H2: Binding and Structural Insights
from Computational Study. J. Comput. Chem. 2016, 37, 366.
(737) Chou, C.; Buehler, M. J. Bond Energy Effects on Strength,
Cooperativity and Robustness of Molecular Structures. Interface Focus
2011, 1, 734−743.
(738) Qin, Z.; Buehler, M. Bioinspired Design of Functionalised
Graphene. Mol. Simul. 2012, 38, 695−703.
(739) Knowles, T. P. J.; Oppenheim, T. W.; Buell, A. K.; Chirgadze, D.
Y.; Welland, M. E. Nanostructured Films from Hierarchical Self-
Assembly of Amyloidogenic Proteins. Nat. Nanotechnol. 2010, 5, 204−
207.
(740) Buehler, M. J. Strength in Numbers. Nat. Nanotechnol. 2010, 5,
172−174.
(741) Keten, S.; Buehler, M. J. Geometric Confinement Governs the
Rupture Strength of H-bond Assemblies at a Critical Length Scale. Nano
Lett. 2008, 8, 743−748.
(742) Keten, S.; Xu, Z.; Ihle, B.; Buehler, M. J. Nanoconfinement
Controls Stiffness, Strength and Mechanical Toughness of β-Sheet
Crystals in Silk. Nat. Mater. 2010, 9, 359−367.
(743) Nair, A. K.; Qin, Z.; Buehler, M. J. Cooperative Deformation of
Carboxyl Groups in Functionalized Carbon Nanotubes. Int. J. Solids
Struct. 2012, 49, 2418−2423.
(744) Compton, O. C.; Cranford, S. W.; Putz, K. W.; An, Z.; Brinson,
L. C.; Buehler, M. J.; Nguyen, S. T. Tuning the Mechanical Properties of
Graphene Oxide Paper and Its Associated Polymer Nanocomposites by
Controlling Cooperative Intersheet Hydrogen Bonding. ACS Nano
2012, 6, 2008−2019.
(745) Qin, Z.; Buehler, M. J. Cooperative Deformation of Hydrogen
Bonds in Beta-Strands and Beta-Sheet Nanocrystals. Phys. Rev. E 2010,
82, No. 061906.
(746) Hu, X.; Xu, Z.; Gao, C. Multifunctional, Supramolecular,
Continuous Artificial Nacre Fibres. Sci. Rep. 2012, 2, 767.
(747) Hsu, S.; Lin, Y.; Chang, J.; Liu, Y.; Lin, H. Intramolecular
Interactions of a Phenyl/Perfluorophenyl Pair in the Formation of
Supramolecular Nanofibers and Hydrogels. Angew. Chem., Int. Ed. 2014,
53, 1921−1927.
(748) Hirst, A. R.; Coates, I. A.; Boucheteau, T. R.; Miravet, J. F.;
Escuder, B.; Castelletto, V.; Hamley, I. W.; Smith, D. K. Low-Molecular-
2824
Review
Weight Gelators: Elucidating the Principles of Gelation Based on
Gelator Solubility and a Cooperative Self-Assembly Model. J. Am. Chem.
Soc. 2008, 130, 9113−9121.
(749) Rest, C.; Mayoral, M. J.; Fucke, K.; Schellheimer, J.; Stepanenko,
V.; Fernández, G. Self-Assembly and (Hydro)gelation Triggered by
Cooperative π−π and Unconventional CH···X Hydrogen Bonding
Interactions. Angew. Chem., Int. Ed. 2014, 53, 700−705.
(750) Song, G.; Zhang, L.; He, C.; Fang, D.; Whitten, P. G.; Wang, H.
Facile Fabrication of Tough Hydrogels Physically Cross-Linked by
Strong Cooperative Hydrogen Bonding. Macromolecules 2013, 46,
7423−7435.
(751) Carrillo, R.; López-Rodríguez, M.; Martín, V. S.; Martín, T.
Crystal Structures of Self-Assembled Nanotubes from Flexible Macro-
cycles by Weak Interactions. CrystEngComm 2010, 12, 3676−3683.
(752) Tokmachev, A. M.; Dronskowski, R. Hydrogen-Bond Networks
in Finite Ice Nanotubes. J. Comput. Chem. 2011, 32, 99−105.
(753) Oh, H.; Sim, J.; Ju, S. Binding Affinities and Thermodynamics of
Noncovalent Functionalization of Carbon Nanotubes with Surfactants.
Langmuir 2013, 29, 11154−11162.
(754) Jin, W.; Fukushima, T.; Niki, M.; Kosaka, A.; Ishii, N.; Aida, T.
Self-Assembled Graphitic Nanotubes with One-Handed Helical Arrays
of a Chiral Amphiphilic Molecular Graphene. Proc. Natl. Acad. Sci. U. S.
A. 2005, 102, 10801−10806.
(755) Datta, A.; Pati, S. K. Dipolar Interactions and Hydrogen Bonding
in Supramolecular Aggregates: Understanding Cooperative Phenomena
for 1st Hyperpolarizability. Chem. Soc. Rev. 2006, 35, 1305−1323.
(756) Gray, T.; Kim, T.; Knorr, D. B., Jr.; Luo, J.; Jen, A. K.-Y.;
Overney, R. M. Mesoscale Dynamics and Cooperativity of Networking
Dendronized Nonlinear Optical Molecular Glasses. Nano Lett. 2008, 8,
754−759.
(757) Knorr, D. B., Jr.; Benight, S. J.; Krajina, B.; Zhang, C.; Dalton, L.
R.; Overney, R. M. Nanoscale Phase Analysis of Molecular
Cooperativity and Thermal Transitions in Dendritic Nonlinear Optical
Glasses. J. Phys. Chem. B 2012, 116, 13793−13805.
(758) Suponitsky, K. Y.; Masunov, A. E. Supramolecular Step in
Design of Nonlinear Optical Materials: Effect of π···π Stacking
Aggregation on Hyperpolarizability. J. Chem. Phys. 2013, 139,
094310−16.
(759) Mafé, S.; Manzanares, J. A.; Reiss, H. Nanoscale Switch Based on
Interacting Molecular Dipoles: Cooperativity can Improve the Device
Characteristics. J. Appl. Phys. 2011, 109, No. 044302.
(760) Brunelli, N. A.; Didas, S. A.; Venkatasubbaiah, K.; Jones, C. W.
Tuning Cooperativity by Controlling the Linker Length of Silica-
Supported Amines in Catalysis and CO2 Capture. J. Am. Chem. Soc.
2012, 134, 13950−13953.
(761) Bouteiller, L.; Colombani, O.; Lortie, F.; Terech, P. Thickness
Transition of a Rigid Supramolecular Polymer. J. Am. Chem. Soc. 2005,
127, 8893−8898.
(762) White, S. L.; Smith, J. G.; Behl, M.; Jain, P. K. Cooperativity in a
Nanocrystalline Solid-State Transition. Nat. Commun. 2013, 4, 2933.
(763) Düring, J.; Hölzer, A.; Kolb, U.; Branscheid, R.; Gröhn, F.
Supramolecular Organic−Inorganic Hybrid Assemblies with Tunable
Particle Size: Interplay of Three Noncovalent Interactions. Angew.
Chem., Int. Ed. 2013, 52, 8742−8745.
(764) Sikder, Md. D. H.; Gibbs-Davis, J. M. The Influence of Gap
Length on Cooperativity and Rate of Association in DNA-Modified
Gold Nanoparticle Aggregates. J. Phys. Chem. C 2012, 116, 11694−
11701.
(765) Liu, J.; Lu, Y. Smart Nanomaterials Responsive to Multiple
Chemical Stimuli with Controllable Cooperativity. Adv. Mater. 2006, 18,
1667−1671.
(766) Busseron, E.; Ruff, Y.; Moulin, E.; Giuseppone, N. Supra-
molecular Self-Assemblies as Functional Nanomaterials. Nanoscale
2013, 5, 7098−7140.
(767) Liu, W.; Wang, Q.; Wang, Y.; Huang, Z.; Wang, D. Designed
Self-Assemblies Based on Cooperative Noncovalent Interactions
Including Anion−π, Lone-Pair Electron−π and Hydrogen Bonding.
RSC Adv. 2014, 4, 9339−9342.
DOI: 10.1021/cr500344e
Chem. Rev. 2016, 116, 2775−2825
Chemical Reviews Review

(768) Kumagai, T.; Hanke, F.; Gawinkowski, S.; Sharp, J.; Kotsis, K.;
Waluk, J.; Persson, M.; Grill, L. Controlling Intramolecular Hydrogen
Transfer in a Porphycene Molecule with Single Atoms or Molecules
Located Nearby. Nat. Chem. 2013, 6, 41−46.
(769) Suttipong, M.; Grady, B. P.; Striolo, A. Self-Assembled
Surfactants on Patterned Surfaces: Confinement and Cooperative
Effects on Aggregate Morphology. Phys. Chem. Chem. Phys. 2014, 16,
16388−16398.
(770) Xavier, P.; Bose, S. Non-Equilibrium Segmental Dynamics
Driven by Multiwall Carbon Nanotubes in PS/PVME Blends. Phys.
Chem. Chem. Phys. 2014, 16, 9309−9316.
(771) Bharati, A.; Xavier, P.; Kar, G. P.; Madras, G.; Bose, S.
Nanoparticle-Driven Intermolecular Cooperativity and Miscibility in
Polystyrene/Poly(vinyl methyl ether) Blends. J. Phys. Chem. B 2014,
118, 2214−2225.
(772) Wei, X.; Nangreave, J.; Liu, Y. Uncovering the Self-Assembly of
DNA Nanostructures by Thermodynamics and Kinetics. Acc. Chem. Res.
2014, 47, 1861−1870.
(773) The Fourth Paradigm: Data-Intensive Scientific Discovery; Hey, T.,
Tansley, S., Tolle, K., Eds.; Microsoft Research, 2009.
(774) Magoulas, R.; Lorica, B. Introduction to Big Data in Release 2.0;
O’Reilly Media: Sebastopol, CA, 2009.
(775) Snijders, C.; Matzat, U.; Reips, U.-D. ″Big Data″: Big Gaps of
Knowledge in the Field of Internet Science. Int. J. Internet Sci. 2012, 7,
1−5.

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