Crystal Engineering

Dr. Manjit K. Bhattacharyya

Professor
Department of Chemistry
Cotton University
• Crystal engineering is a rapidly growing research topic with
goals aimed at designing functional molecular solids using
intermolecular interactions.

• By designing these molecular solids using principles of

supramolecular chemistry, desired molecular arrangements
can be achieved with potential applications.

• The term was first introduced by Pepinsky in 1955,

however, the idea of „engineering‟ a crystal originated in
solid-state photochemistry.
• Crystal engineering represents a paradigm for synthesis of
new solid state architectures with predictable stoichiometry
and properties.

• Crystal engineering is associated with three aspects; structure

analysis, structure design and property engineering.

• Structure analysis explains the way by which the subject was

started in the early days to correlate structure with property.
This was the first phase or generation of crystal engineering;
which was concerned with the study of molecular organization in
terms of intermolecular interactions
• Then a systematic protocol, in terms of a logic
driven methodology, was presented to achieve a
targeted structure, with the supramolecular synthon
being a facilitating concept. In this phase, property
is not targeted explicitly; it is the target structure
that is important.

•However, there was no prediction of crystal

property in the 1st two stages of crystal engineering.
• Researchers have shifted their attention to the third
generation of crystal engineering recently and explored the
property engineering of organic and metal-organic
crystalline solids

• The first and second generations have been well studied

over the last 50 years and work in these aspects continues
even today

• The third generation of crystal engineering has only just

begun with some recent examples of differently engineered
crystals (till now restricted to mechanical properties)
Development of crystal engineering through different generations
Categories of soft organic crystals.
Molecular structure of [Cu(H2PO4)2(phen)(H2O)]·2H2O

1st generation of crystal engineering deals with the

structural analysis of the compound
Molecular structure of
[Cu2(HL)(L)(N3)3]·2H2O

L = 1-(2-aminoethyl)
piperazine

Supramolecular
synthon formed by
H-bonding
interactions which
stabilizes the 2D
assembly of the
compound.
• Molecular structure of
[Cu(Orotate)(H2O)2]

• 2D assembly of the compound

assisted by unusual Cu…O
interactions
• Supramolecular synthons are spatial arrangements of
intermolecular interactions that play a focusing role in the
supramolecular syntheses and are similar to conventional
synthons in molecular synthesis.

• The use of hydrogen bonding and dispersion forces as well

as directional interactions including stacking can be used
as tools or design elements in crystal design.
Because of the great significance of supramolecular
synthons in molecular synthesis, their identification and
analysis in terms of crystallographic, spectroscopic, and
computational methods is very essential.

Depending on their properties, supramolecular synthons

have evolved to become a useful tool for the synthesis
of materials derived from molecular building blocks.
Hydrogen-bonding motif in which amide and pyridine moieties
• Among many interesting properties of molecular crystals,
flexibility of crystals is a rapidly growing research field.

• These crystals are of two major types namely plastic and

elastic.

• Plasticity is the result of anisotropic crystal packing whereas

isotropic interactions along orthogonal directions generate
elasticity.

• Anisotropic crystal packing represents the quality of the

crystal to exhibit different properties when measured along
axes in different directions.
• These properties are eliciting greater interest
because of their application to many other fields such
as pharmaceuticals, muscle-mimetic biomaterials,
artificial mechanosensors, molecular machinery,
optical devices, organic electronics, smart
nanomaterials.

• A supramolecular capping based strategy has been

recently used to convert brittle crystals into elastic
crystals.
• σ/π-holes can be defined as the regions of positive electrostatic
potential found on an (partially) empty anti-bonding σ*/π* orbitals.
• Both σ- and π-hole interactions are very similar in nature
•are typical examples oCarbonyl···carbonyl and nitro···nitro orthogonal
interactions f such π-hole based synthons.
• Application of this provides an advanced methodology for the
design of elastic crystals following third generation crystal
engineering.
 Stacked supramolecular sheets (red and black) are
connected through σ-hole interactions and by π-hole
contacts.
Bending crystal of [3,5-dichlorosalicylic acid][3,5-bromopyridine]

Bending crystal of [3,5-dinitrobenzoic acid][4-pyridinecarboxaldehyde]

A general mechanism is
suggested to explain
elasticity of these crystals.

This indicates that changes

are required in the distances
and angles at the bent site
for the σ- and π-hole
contacts.

These changes will be

allowed with the retention of
crystallinity, if the system
still can hold similar
stabilization at that
deformed situation.
(a) Weak Cl···Cl interactions in 3,4-dichlorophenol replaced by (c)
stronger Br···Br interactions in 4-bromo-3- chlorophenol; (b) plastic
→ (d) elastic change via increased structural isotropy
Bending crystals of Hexachlorobenzene assisted by weak Cl···Cl
interactions

The bending in the hexachlorobenzene is anisotropic in that the

crystals may be deformed only along [001] plane
Bending crystals of 1,4-bis(thien-2-yl)-2,4,5,6-tetrafuorobenzene

The elastic and flexible nature of the crystal may be due to the
presence of delocalized π-systems (π-conjugated molecules); which
have been reported to be highly useful compared with those with
localized systems (non-conjugated molecules).
 The supramolecular
assembly of [Cu(acac)2]
is facilitated by π-π
interactions of
delocalized electronic
systems and by
relatively strong Cu-π
interactions.

Bent crystals of [Cu(acac)2]

(acac = acetylacetonate)
 [PbBr2(3Fspy)2]n (3F-spy = 3-fluoro-4′-styrylpyridine)

The 1D polymeric chains are interlinked together by CH···F and C-

H···Br interactions. Due to the presence of such “strong”
interactions between the neighboring chains, the 1D chains are
interlocked, and elastic deformation upon application of an
external force.
 A series of “strong” non-covalent
interactions such as,
halogen···halogen, C-H···N, and C-
H···Cl interactions are present in
the crystal structure; which play
pivotal role in the elasticity of
the crystal.

[Zn(m-Cl)2(3,5-dichloropyridine)2]n
 Smart Materials
• Smart materials are the materials that can significantly alter
one or more of their inherent properties owing to the
application of an external stimuli in a controlled fashion.

• The several external stimulus to which Smart materials are

sensitive are:

• External stress

• Temperature

• Moisture

• pH

• Magnetic fields etc.

Types

• Piezoelectric materials are very common

example of such materials where they produce a
voltage when external stress is applied

• Thermo-responsive materials, either Shape

Memory Alloys (SMA) or shape memory
polymers, are materials that can hold different
shapes at various temperatures.

• Magneto restrictive materials similar to piezo-

electrics, respond to only magnetic fields rather
than electric.
• pH-sensitive materials are the materials that
change their colour as a result of changing
acidity.

• Polymer gels, such as hydrogels, have a cross

linked polymer structure inflated with a
solvent, such as water; the gel has the ability
to swell or shrink (up to 1000 times in volume)
due to small changes in, e.g., temperature or
pH.
• The unique properties of smart polymers have long been gaining
attention and investigation from both academics and industry.

• The characteristics of different polymers rely on how the long

chains of the molecules repeat themselves and bond with each
other.

• The inherent structure, along with the way molecules arrange

themselves and cross-link, aids materials‟ responsiveness to
environmental changes.

• Intelligent/Smart polymers are the polymers that are

responsive to single or multiple stimuli, which could be either
chemical or physical
An overview of intelligent polymer development
Historical and emerging tendencies of engineering materials
• Smart polymers are widely used in the biomedical fields,
aiming to develop new therapies for disease treatment or
cautiously designed medical devices that react to
surrounding tissues or external stimuli.

• Polymer-based nano-carriers enable controlled drug

delivery at the right place and right time.
• As a promising approach especially in cancer treatments,
localized drug delivery carriers made by polymers
decrease the toxicity of the drug and via site-specific
release, enhance the effect of the active compounds.

• Current research interests includes minimizing the

degradation of pharmaceutically active ingredients during
the transporting process and optimizing the formulation
methodology of nano-particles with better release
precision
• Deshpande et al. have developed a temperature
dependent drug-delivery system with sustained
release at the target sites.

• Doxorubicin (anticancer drug) was triggered with

gold nano gel particles for the accurate release in
target breast cancer cell lines (HeLa).
• Micro- and nano-scale coordination polymer particles can be used
for encapsulating and accurately delivering drugs at the target
sites.

• In vitro cancer cell cytotoxicity assays showed that encapsulated

drugs in coordination polymer networks can effectively get released
at target cells, which shows anticancer efficacy.

Encapsulation of drugs into metal–organic spheres created by the

connection of metal ions, such as Zn2+, through organic ligand bix