Supramolecular Chemistry

2nd Lecture note, SkJ

03.8.2020
Chiral recognition

The most important aims of molecular recognition is chiral recognition because

it is commonly achieved in biological systems.
Receptors in our body easily distinguish between two molecules that have
same chemical composition but different structure around a chiral carbon
atom.
For example, we sense a sweet test for D-glucose, but L-glucose testes totally
different.
Cram demonstrated the chiral recognition of an ammonium guest using a
crown ether with axis-chiral binapthyl groups.

Chiral recognition using a crown ether

When the (s,s)-host binds to a chiral guest (s- and R --phenylethylammonium

ions), the complexes are thermodynamically different and having different
stabilities.
Binding of the R-guest to the (s,s)-host satisfies steric requirements, because
the phenyl group, the methyl group and the hydrogen can occupy the large,
medium and small sites of the crown, respectively. This complex should be
stable. In contrast, the S-guest cannot fill the sites in this desirable manner due
to its different stereochemistry. The R-guest is therefore selectively recognized
by this host.

Transformation (Function of supramolecule)

Supramolecular reactivity and catalysis

Reactivity and catalysis represent major features of the functional properties

of supramolecular system. Molecular receptors bearing appropriate reactive
groups in addition to binding sites, may complex a substrate (with given
stability, selectivity and kinetic features), react with it (with given rate,
selectivity, turnover) and release the products, thus regenerating the reagent
for a new cycle.

Supramolecular reactivity and catalysis thus involve two main steps: binding
which selects the substrate, followed by transformation of bound species into
products within the supramolecule formed.
Both steps take part in the molecular recognition of the productive substrate
and require the correct molecular information in the reactive receptor.
Compared to molecular reactivity, a binding step is involved that precedes the
reaction itself. Catalysis additionally comprises a third step, the release of the
substrate.

Catalysis by reactive cation receptor molecules

Ester cleavage processes have been most frequently investigated in enzyme

model studies. Macrocyclic polyethers fitted with side chains bearing thiol
groups cleave activated esters with marked rate enhancements and chiral
discrimination between optically active substrates.

The tetra-(L)-cysteinyl derivative of macrocycle (M) binds p-nitrophenyl esters

of aminoacids and peptides and reacts with the bound species, releasing p-
nitrophenol.
The reaction displays
i) Substrate selectivity
ii) Marked rate enhancements in favour of dipeptide ester substrates,
iii) Inhibition by complexable metal cations that displace the bound
substrate
iv) High chiral recognition between enantiomeric dipeptide esters
v) Slow but definite catalytic turnover

Catalysis by reactive anion receptor molecule.

The development of anion coordination chemistry and of anion receptor

molecules has made possible to perform molecular catalysis on anionic
substrates of chemical and biochemical interest such as adenosine
triphosphate (ATP).
ATP hydrolysis was found to be catalyzed by a number of protonated
macrocyclic polyamines.
In particular [24]N 6O2 , strongly binds ATP and markedly accelerates its
hydrolysis to ADP and inorganic phosphate over a wide pH range.
 [24]N6O2

The reaction presents first-order kinetics and is catalytic with turn over.
It prceeds via initial formation of a complex between ATP and protonated
[24]N6O2, followed by an intracomplex reaction which may be involve a
combination of acid, electrostatic, and nucleophilic catalysis.

The above structure represents one possible binding mode of the {ATP-
protonated [24]N6O2} complex and indicates how cleavage of the terminal
phosphoryl groups might take place.
A transient intermediate identified as phosphoramidate is formed by
phosphorylation of the macrocycle by ATP and is subsequently hydrolyzed.

In this process catalyst protonated [24]N6O2 presents prototypical ATPase

activity i.e. it behaves as a proto ATpage.
ATPases are enzymes that catalyze the hydrolysis of adenosine triphosphate (ATP) into
adenosine diphosphate (ADP) and a free phosphate ion. This reaction leads to the release of
energy which is used in the cell. This process is essential for all living creatures.

Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-hydrolysis–driven proton

pumps.
The V-ATPases are composed of a peripheral domain (V 1 ) that carries out ATP hydrolysis and an
integral domain (V0 ) responsible for proton transport.
Co-catalysis

Schematic representation of Cocatalysis process: Group transfer and ligation reaction occurring
within the supramolecular complex formed by the binding of substrates to the two macrocyclic
subunits of a macrotricyclic coreceptor molecule.

Coreceptor molecule should be able to perform cocatalysis by bringing

together substrate(s) and cofactor(s) and mediating reaction between them
within the supramolecular structure.

Protonated [24]N6O2 macrocycle was employed as catalyst for the hydrolysis of

acetylphosphate (AcP = CH3COOPO32-), it was found to mediate the synthesis of
pyrophosphate from AcP.
Substrate consumption was accelerated and catalytic with turnover.
 (PN + P)
The result obtained agrees with a catalytic cycle involving the following steps:

i) Substrate AcP binding by the protonated molecular catalyst [24]N6O2

ii) Phosphorylation of protonated [24] N 6O2 within the supramolecular
complex, giving the phosphorylation intermediate PN
iii) Binding of the substrate HPO42- (P)
iv) Phosphoryl transfer from PN to P with formation of pyrophosphate
PP
v) Release of the product and of the free catalyst for a new cycle.

The fact that [24]N 6O2 is a ditopic coreceptor containing two

diethylenetriamine subunits is of special significance for both PN and PP
formation.These subunits may cooperate in binding AcP and activating it for
phosphoryl transfer via the ammonium sites, in providing an unprotonated
nitrogen site for PN formation, as well as in mediating phosphoryl transfer
from PN to P.
Thus [24]N6O2 would combine electrostatic and nucleophilic catalysis in a
defined structural arrangement suitable for PP synthesis via two successive
phosphoryl transfers, displaying protokinase type activity.
The bond making process extends supramolecular reactivity to cocatalysis,
mediating synthetic reactions within the supramolecular entities formed by
coreceptor molecules.