UNIVERSITA’ DEGLI STUDI DI PADOVA
Laurea specialistica in Scienza e Ingegneria dei Materiali
Curriculum Scienza dei Materiali
Chimica Fisica dei Materiali Avanzati
Part 2 – Supramolecular chemistry and molecular
recognition
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Supramolecular chemistry
 ...can be defined as the “chemistry beyond the molecule”,
bearing on the organized entities of higher complexity that result
from the association of two or more chemical species held
together by intermolecular forces. (J.-M. Lehn)
 Molecular interactions form the basis of the highly
specific recognition, reaction, transport, regulation, etc.
processes that occur in biology
Bacteriorhodopsin
Ion channels
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ATP Synthase
2
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Supramolecular chemistry - 2
 However, chemistry is not limited to systems similar to
those found in biology but is free to create unknown
species and to invent novel processes
+
Rotaxane
N
+
O
N
+
N
N
RuII
N
N
N
N
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
III
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Dendrimeric
structure
O
O
O
O
O
O
M O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
+
N
O
O
O
O
O N
O
O
O
O
6+
O
O
O
O
O
O
O
O
O
O
O
O O
O
O
O
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Coordination bonding
 The scope of coordination chemistry extends to the binding of all
kinds of substrates: cationic, anionic and neutral molecular
species of either organic, inorganic, or biological nature (J.-M.
Lehn)
Cl
OC
N
N
N Zn N
N
RuII
Cl
Cl
N
II N
OC Ru CO
Cl
N
CO
N
N
N Zn N
N
N
NH N
NH N
N HN
N HN
Cl
OC II CO
Ru
N
N
Cl
N
N
N Zn N
N
N
OC
Cl
RuII N
CO
Cl
N
N
N Zn
N
N
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Molecular recognition
 Molecular recognition is defined by the energy and the
information involved in the binding and selection of
substrate(s) by a given receptor
 It implies the (molecular) storage and supramolecular read
out of molecular information
Selective binding of a substrate by a receptor
Selection =
Interaction =
INFORMATION
ENERGY
 receptor and substrate should exhibit





Steric complementarity (shape and size)
Interactional complementarity
Large contact areas
Multiple interaction sites
Strong overall binding
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At the origin of molecular recognition
 1894: Emil Fischer presents the ‘lock and key’ model
for enzymatic chemistry 
 Molecular recognition
 Supramolecular function
Structure of glutamine synthetase: a homododecamer
Active site
Binding of Ritonavir
inhibitor to a protease
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Spherical recognition
 Recognition of metal cations
 Spherical guests: metal cations (Na+, Ca2+, La3+) and halide anions (Cl-, I-,
etc.)
R
+ Ca2+
R
O
O
O
O
O
O
R
R
O
O
O Ca2+ O
O
O
Crown Ethers
Charles Pedersen, 1967
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Rotaxanes
 A case of ingenious use of [NHO] and [NCHO] H-bonds
between di-alchil-ammonium cations and crown ethers
J. Fraser Stoddart et al. (UCLA)
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Rotaxanes as molecular machines
Shuttling action by cemical
chemical stimulation
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Catenanes
With the same
interactions it is
possible to obtain a
different type of
interlaced structure:
the catenanes
Proposed mechanism:
1.
Formation of a tri-cationi
intermediate
2.
Formation of a charge
transfer complex
3.
Self-assembly promotes the
interlaced structure
4.
The catenane is afforded (in
a 70% yield)
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Molecular recognition portfolio: cavitands
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Anatomy of cyclodextrins
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Bonding by hydrophobic effect
Solvated host
Solvated guest
Complex
The hydrophobic effect
 Strong inclination of water molecules to form H-bonds with each other
affects their interacn. with non-polar molecules not forming H-bonds
(alkanes, hydrocarbons, fluorocarbons, etc.)
 Water molecules can pack around the non-polar solute without giving
up any of their H-bonding sites (however, the size and shape of nonpolar molecules is very critical)
 The net effect is a reorientation of the water molecules towards a
structure more ordered that in the bulk liquid.
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The hydrophobic effect (cont’d)



The increased order in the water cages
is entropically unfavourable.
For this reason, the hydrocarbons are
very little soluble in water: the free
energy increases due to the decrease in
entropy
The free energy of solubilization is
roughly proportional to the surface area
of the molecules.
The hydrophobic interaction
It arises primarily from the rearrangement of H-bond configurations in the
overlapping solvation zone as two hydrophobic species come together.
 It is a cooperative effect of much longer range than any typical bond
 The hydrophobic interaction plays a central role in many surface phenomena, in
molecular self-assembly, in micelle formation, in biological membrane structure
and in determining the conformation of proteins.
Example:
2

E surface tension   15  30 mJ/m
E interfacia l tension   40  50 mJ/m 2
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Application: Molecular-recognition-based Sensors
 Technology need: sensors which can distinguish extremely low
level of gas species in the presence of large quantities of
interfering species
 Required features: sensitivity, selectivity, response time
 Proposed solution: sensing chemicals by analysis of changes in
the refractive index of a thin film of host reagent on a waveguide
caused by the formation of guest-host inclusion complexes in the
thin film.
 Advantages:Because the formation of inclusion complexes is
reversible, the sensor apparatus can be used for substantially
real-time sensing of chemical agents. Sensor sensitivity can be
tuned and choice of chemicals to be detected can be made by
varying the size of the host reagent cavities and by selecting the
chemical functionality of the host reagent molecules.
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Application: Molecular-recognition-based Sensors - 2
WAVEGUIDE BASED OPTICAL CHEMICAL SENSOR
Abstract
The invention provides an apparatus and method for highly selective and
sensitive chemical sensing. Two modes of laser light are transmitted through
a waveguide, refracted by a thin film host reagent coating on the waveguide,
and analyzed in a phase sensitive detector for changes in effective refractive
index. Sensor specificity is based on the particular species selective thin
films of host reagents which are attached to the surface of the planar optical
waveguide. The thin film of host reagents refracts laser light at different
refractive indices according to what species are forming inclusion complexes
with the host reagents.
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