Supramolecular chemistry

chemistry of supramolecules,An interesting subject for those who love chemistry..

1. Supramolecular Chemistry
THOSHINA THOMAS
KEYI SAHIB TRAINING COLLEGE
TALIPARAMBA

2. Supramolecular chemistry, a term introduced by Jean-
Marie Lehn, is “chemistry beyond the molecule”,
i.e. the chemistry of molecular assemblies using
noncovalent bonds.
Nobel Prize in 1987: Pederson C , Cram D J, Lehn J M.
Introduction:

3. In 1967, Pedersen observed that crown ether showed
molecular recognition – the first artificial molecule found
to do so.
Cram established, host–guest chemistry, where the
host molecule can accommodate another guest
molecule.
In 1978, Lehn proposed the term “supramolecular
chemistry”.
Together, Pedersen, Cram and Lehn received the
Nobel Prize for Chemistry in 1987.

4. Lessons from nature--
DNA bound by base pairs

5. Supramolecular chemistry – in nature

6. Introduction:
“Supramolecular chemistry” - “chemistry beyond the
molecule”
According to Dr. Lehn, who invented the term, a
supermolecule formed by the association of two or more
chemical species held together by intermolecular forces.
Like..
hydrogen bonding, hydrophobic interactions and coordination.

7. •focuses on non-covalent bonding interactions focuses on non-covalent bonding interactions
of molecule.of molecule.
•Forces include hydrogen bonding, metal Forces include hydrogen bonding, metal
coordination, Van der Waals forces, pi-pi coordination, Van der Waals forces, pi-pi
interactions, electrostatic effects…interactions, electrostatic effects…
Intermolecular and intramolecular forces

8. Intermolecular Bonding
Bonding between molecules
van der Waals forces
•Hydrogen bonding
–This relatively strong type of inter-molecular bonding
between a hydrogen atom and an electron pair or
electronegative atom.
–Multiple hydrogen bonds hold the DNA double helix
together.
•Dipole interaction
•London forces
–These are induced forces caused by a temporary
rearrangement of the electron clouds when molecules
bump together.

9. Supramolecular chemistry –
the forces

10. Hydrogen
Bonding
H
O
H
O
H
H
O
H
H

11. Dipole Interaction
•The partial positive and negative ends of
the molecules hold the molecules
together.

12. London Dispersion Forces (LDF)
instantaneous dipole–induced
dipole forces,
London forces are induced dipoles
caused by temporary
rearrangement of the electron
cloud.

14. Assembled by π-π interaction
Some simple models:
Cation–π
interaction bn
benzene and a
Na cation.
Polar π
interaction bn
water molecule
and benzene
Π - π
interaction bn
e rich benzene
& e poor
hexafluorobenz
ene

15. Assembled by metal-ligand
P. J. Stang, Chem. Eur. J., 1998, 4, 19-27

16. Assembled by metal-ligand
Nanosized cavities.
J. Manna, P. J. Stang, J. Am. Chem. Soc. 1996, 118, 8731.

17. Assembled by metal-ligand
Twelve units come together precisely
with high yield: A Remarkable reaction
P. J. Stang, N. E. Persky, J. Manna, J. Am. Chem. Soc. 1997, 119, 4777.

18. Classification of Supramolecules
molecular recognition
chemistry
chemistry associated with
a molecule recognizing a
partner molecule
chemistry of
molecules
built to
specific
shapes
chemistry of
molecular
assembly from
numerous
molecules
“lock and key”
host–guest chemistry
Molecular recognition chemistry (host–guest chemistry) +
chemistry of molecular assemblies + chemistry of molecular
associations ® “supramolecular chemistry”
[Amphiphilic
molecules –
micelles, lipids..]
[Rotaxane, catenane,
Dendrimers,
Fullerene, CNTs..] [Crown ether, Polyamines,
Cyclodextrin, calixarne..]

19. “lock and key”

20. Host-guest chemistry

21. Supramolecular chemistry – lock-and-key

22. Different Supermolecules

23. Chemists Interested In Such
systems
 Early 1970 molecular recognition in biological systems attracted
synthetic chemists.
 1967 discovery of crown ethers.
(Charles Pederson).
As 0.4% impurity !
[18] crown-6 a host for K
+

24. Host-Guest chemistry is an example of supramolecular chemistry.

Molecular assembly!?
Human made DNA
Chemical level

25. Host Molecules
1) Crown Ethers:
Crown ethers were the first artificial host molecules discovered.
They were accidentally found as a byproduct of an organic reaction.
When Pedersen synthesized bisphenol, contaminations from
impurities led to the production of a small amount of a cyclic
hexaether

26. Pedersen called the cyclic compound a crown
ether, because the cyclic host “wears” the ion
guest like a crown.
Crown ethers are named as follows: the number before “crown”
indicates the total number of atoms in the cycle, and the number after
“crown” gives the number of oxygen atoms in the cyclic structure. The
oxygen atom, which has a high electronegativity, can act as a binding
site for metal ions and ammonium ions through dipole–ion
interactions.

27. Crown ethers are classified by structural types: noncyclic hosts
are known as podands; monocyclic hosts including crown
ethers are called coronands; oligocyclic hosts are termed
cryptands.
Cryptands have a motion-restricted cyclic structure; they can
accommodate only strictly size-matched guest molecules.

28. 2) Macrocyclic Polyamines – Nitrogen-Based Cyclic Hosts:
Replacing the oxygen atoms in the crown ethers by nitrogen atoms -
macrocyclic polyamines.
Strong basic nature of the amine group results in unique host
properties.
Thioether-type crown compounds (crown ethers with sulfur atoms
instead of oxygen atoms) are called as thiacrowns.

29. 3) Cyclodextrin – A Naturally Occurring Cyclic Host:
Cyclodextrins can be obtained from starch (polysaccharide with an α
1–4 linkage of glucose) via certain enzymes.
The enzyme changes this polysaccharide into a cyclic oligomer with
an appropriate number of glycopyranoside units.
6,7,8 glycopyranside units (are called α-, β- and γ -cyclodextrin,
respectively)

30. Structural design:
Primary hydroxyl groups are located at the side of a narrow inlet,
while secondary hydroxyl groups are found on the reverse side (at
the side of a wide inlet).
Therefore, no hydroxyl groups exist on the wall, and so the cavity of
the cyclodextrin is hydrophobic.
Cyclodextrins dissolved in an aqueous phase can accommodate
hydrophobic guests such as aromatic hydrocarbons (benzene),
inorganic ions & gas molecules in their cavities.

31. Structure of a cyclodextrin and some pore diameters

32. Dimer naphthalene formation results in stronger emission
Inclusion of a guest inside the cavity of a cyclodextrin induces light emission

33. Hydrolysis of phenyl acetate by cyclodextrin to phenol & acetate
artificial enzyme, where a cyclodextrin cavity works as a hydrophobic
binding site and hydroxyl groups play the role of a catalytic residue.

34. 4) Calixarene– A Versatile Host:
Calixarenes are macrocyclic host molecules made from phenol
units linked through methylene bridges.
name “calixarene” reflects the structures of these molecules, since
a calix is a chalice (trophy).
Calix[n]arene
Calix[4]arene

35. Calixarenes:
 macrocycles that are made from phenol or P-tert-butylphenol.
Calix[4]arene Calix[8]areneCalix[6]arene

36. Different views of calix[4]arene
~ 3-7 Å
width

37. The isomers vary in terms of the orientations of their phenol groups:
(a)has a cone structure with all of the phenols pointing to the same
direction;
(b) has a partial cone structure with one phenol pointing in a
different direction to the others;
(c) has a 1,3-alternate structure with neighboring phenols pointing in
opposite directions.
Confirmation isomers of Calix[4]arene

38. The calix[8]arene depicted in Fig. can bind fullerenes
Binding of fullerene by Calix[8]arene
The calix[8]arene has a cavity with an inner diameter of 1nm, which is
∼
therefore suitable for C
60
, since it has a diameter of 0.7nm. So in the
∼
figure 10 we can see the fullerene “soccer ball” is trapped in the calix.

39. 5) Cyclophane– 3 dimensinal cavitied Host:
Cyclophanes are cyclic hosts made from aromatic rings that
recognize hydrophobic guest molecules. Three dimensional
cavities can be constructed by attaching tails, walls and caps to
the cyclic hosts.

40. Endoreceptors and Exoreceptors
According to Lehn’s definition, host molecules that have binding
sites inside their molecular structures (cavities) are called
endoreceptors.
For example, enzymes are generally endoreceptors, because
they recognize the guest substrate in a reaction pocket located
inside the enzyme.
Host molecules with guest binding sites on their surfaces are
defined as exoreceptors.
Antibodies are classified as the exoreceptors because they
recognize antigen on the terminal surface.

41. Classification of Supramolecules
molecular recognition
chemistry
chemistry associated with
a molecule recognizing a
partner molecule
chemistry of
molecules
built to
specific
shapes
chemistry of
molecular
assembly from
numerous
molecules
“lock and key”
host–guest chemistry
Molecular recognition chemistry (host–guest chemistry) +
chemistry of molecular assemblies + chemistry of molecular
associations ® “supramolecular chemistry”
[Amphiphilic
molecules –
micelles, lipids..]
[Rotaxane, catenane,
Dendrimers,
Fullerene, CNTs..] [Crown ether, Polyamines,
Cyclodextrin, calixarne..]

42. Medium-size with Specific shape supermolecules
These supermolecules have interesting and unique
geometric features.
Some examples (are nanoparticles) include
Fullerenes,
Carbon nanotubes,
Dendrimers,
and Rotaxanes, Catenanes etc.

43. 1. FULLERENES
•One example is the Buckminsterfullerene
(Buckyball)
•It has a formula C
60
•It is a black solid
•Dissolves in petrol to make a
red solution
•Free moving electrons so conducts
electricity
They are spheres of only carbon atoms and are also allotropes of
carbon

44. Buckminsterfullerene C
60
, also known as the buckyball, is the
smallest member of the fullerene family.
Metal-doped fullerene can therefore be regarded as a “superatom”.
Doped fullerenes are also known to exhibit superconductivity.
C
60
Metal-doped fullerene

45. CARBON IN DIFFERENT DIMENSIONS
3 D CARBON
2 D CARBON
Graphene

46. Iijima, 1991

47.  NANO TUBES ARE TINY
TUBES OF CARBON ABOUT
10,000 TIMES THINNER
THAN HUMAN HAIR.
 THESE CONSIST OF
ROLLED UP SHEETS OF
MULTI LAYER CARBON
ATOMS IN HEXAGON SHAPE.
THEY CONDUCT
ELECTRICITY BETTER THAN
COPPER AND ARE MORE
STRONGER THAN STEEL
WIRE .
Carbon nanotubes can store
huge volumes of gas
Carbon nanotubes can also be used
as tips in probe microscopy.

48. Single wall Nanotubes
Multi wall Nanotubes

49. Preparation
Preparation of nanomaterials is commonly referred as
Nanofabrication.
Two approaches used for fabricating to nano scale particles are
Top-down nanofabrication and Bottom-up nanofabrication.
Top-down method involves carving bulk to desired size.
Techniques used to perform this method are Precision Engineering
and Lithography.
The bottom-up method involves building up of materials atom by atom
or molecule by molecule.
Positional assembly and Self-assembly, are the techniques

50. TOP DOWN method
From large to small
Nanoscale structures by
cutting down materials to
smaller and smaller sizes
BOTTOM UP method
From small to large
Things are made by building
up from the atomic scale.
How to make nanomaterials

51. 3. Dendrimers – Molecular Trees
Dendrimers have systematic branching structures and
they are built in a stepwise manner.
The word “dendrimer” contains “dendr-”, which means
tree. So it can be treated as a molecular trees
or they are nano sized polymers.
Dendrimers are constructed by stepwise connection of
several parts (divergent method and convergent
method).

53. Porphyrin unit
immobilized in a
dendrimer
Dendrimer
Porphyrin

54. Star-shaped dendrimers can also be synthesized, using stepwise dendrimer
growth and subsequent linear polymerization

55. 4. Rotaxanes–Threading Molecular Rings
Rotaxanes are obtained by threading linear polymers through
molecular rings such as cyclodextrins, crown ethers and cyclophanes.
The word “rotaxane” means wheel axle (rota = wheel, axis = axle).
Structurally, they consist of molecular rings threaded by molecular
wires that have stoppers at both ends to keep the rings in place.
When more than one ring is threaded by a single wire, the structure
is called a polyrotaxane. Sometimes we encounter a rotaxane with
no stoppers; these molecules are called pseudo-rotaxanes.

56. These structures occur in naturally-occurring systems (some DNA
enzymes are ring-shaped, and the DNA chain passes through the
enzyme ring).
In 1960s researchers discovered artificial rotaxane structures by
stepwise process
Cyclodextrin-based rotaxane

57. 5 Catenanes– Complex Molecular Associations
Catenanes consist of two or more interlocked rings. (Latin word
“catena”, means linked chains.)
Although the interlocked rings in catenanes are not bonded together
by covalent bonds, they cannot be separated from each other.
Strategies for catenane synthesis

58. Molecular Self Assembly –Building Supermolecules
Supramolecular assemblies- The supermolecules result
from self-assembling (or self-organizing) processes.
Molecular Self Assembly –Building Supermolecules
fuzzy
molecular
interaction.
programmed assembly
(precisely defined
recognition)

59. Programmed Supramolecular Assembly: Precise…
For example, the three-dimensional structures of
proteins are defined by their amino acid sequences; in
other words, the structure of a protein is programmed in
its amino acid sequence.
Supramolecular Assembly via Fuzzy Interactions:
Fuzzy (unclear or un precise) interactions, sometimes
produce more flexible, sensitive and adaptable
functionality.
Eg. cell membranes,

60. Supramolecular chemistry – self
assembly

61. Programmed Supramolecular Assembly
“Precisely programmed” structural information in the unit
structure.
For example,
the three-dimensional structures of proteins are defined by
their amino acid sequences; or, the structure of a protein
is programmed in its amino acid sequence.

62. For example, exact DNA replication relies
upon complementary hydrogen bonding
between nucleobases.
In programmed systems, the structural information in
the units must be transferred precisely to the
assembly.
Several artificial helicates are created similar to DNA
helix.

63. The formation of shape-defined supermolecules requires
direction-specific molecular interactions.
Hyrogen bonding - because hydrogen bonding requires
a specific geometry for the pair of interacting
components.
H- bonding is
important
interaction for
precise
recognition.

64. Supramolecular Assembly via Fuzzy Interactions
Supramolecular assemblies based on less precise
recognition processes sometimes produce more flexible,
sensitive and adaptable functionality.
Cell membranes, are best example of a natural supramolecular
assembly based on fuzzy molecular interactions.
fuzzy (unclear or un-precise)
Other egs. are Micelles, Liposomes, Vesicles, cast
films etc….

65. Simplified illustration of a cell membrane
The structure of the cell membrane comprises lipids that form a double-layer
structure containing floating proteins.

66. Structures and Formation Mechanisms of Cell Membranes:
assembly of mainly lipids and proteins. (eg. lipid bilayer
structure).
The structure of the cell membrane comprises lipids that
form a double-layer structure containing floating proteins.
The major driving force for lipid bilayer formation is
hydrophobic interaction.
A lipid molecule consists of a hydrophilic head and
hydrophobic tail.
Conceptual structure of an amphiphile

67. Amphiphiles - Molecules that have affinities for both
hydrophilic and hydrophobic media. Eg. Lipids
many kinds of artificial amphiphiles are reported to
form membrane-like structures in aqueous media.
When amphiphilic molecules are dispersed in water,
the polar part of the amphiphile tends to expose itself
to bulk water while the hydrophobic part shields itself
from the aqueous phase, forming an assembly through
hydrophobic interactions.

68. Micelles –Dynamic Supramolecular Assemblies
The simplest kind of supramolecular assembly formed by
amphiphiles is the micelle
surfactants or detergents.
Such molecules show relatively high solubility and easily
disperse in water up to a certain concentration level, above
which they form micelles.
This concentration is called the critical micelle
concentration (CMC).

69. Liposomes, Vesicles and Cast Films – Supramolecular
Assemblies Based on Lipid Bilayers
Amphiphilic molecules or lipid molecules sometimes form
double-layer structures.
This structure is called a bilayer structure, and it can be
used to model a cell membrane.
Liposome-like structures formed from various kinds of
amphiphiles are sometimes called “vesicles”, while the
term “liposome” is sometimes limited to assemblies from
phospholipids.
The lipid bilayer structure, the fundamental structural unit
of liposomes and vesicles.

70. Liposomes are lipid bilayer structure extends two-dimensionally
and forms the “skin” of a closed sphere that has a water pool
inside.
This capsule-like structure can be thought of as a simplified
model of a cell.
Liposome or vesicle with a lipid bilayer membrane

71. lipid bilayer behaves as a thermotropic liquid crystal
The gel (or crystalline) to liquid-crystalline transition
temperature at which the change in state occurs is called the
gel (or crystalline)–liquid crystalline phase transition
temperature.

72. Thin films of bilayer forming amphiphiles are called cast
films, has a multilayered lipid bilayer structure.
It is prepared by gradual evaporating water from a solution
of aqueous vesicles on a solid support.

73. Cast film with
a multibilayer
structure

74. The cast film has a structurally anisotropic nature.
It can provide an anisotropic medium for material syntheses.
Using cast film as a template, structurally anisotropic
materials can be synthesized.
Formation of an anisotropic polymer in the interlayer spaces of lipid bilayers

75. Applications of Supermolecules
Supermolecules capable of electron conduction and electrical
switches (molecular electronic devices), supermolecules that
respond to light and manipulate photonic information
(molecular photonic devices), supermolecules that can be
used for information processing and calculations (molecular
computer), and supermolecules that move, rotate, and catch
targets (molecular machines) are introduced as examples of
molecular devices.
Molecular Device is the development of ultra small functional
systems is predicted to enhance our standard of living.

76. Scanning Probe Instruments
Scanning Tunneling Microscope (STM)
Atomic Force Microscope (AFM),
These type instruments are Scanning Probe Instruments.
These microscopes have a nanoscale probe tip, or stylus,
which slides along the sample surface and scans it. In the
functioning of STM the amount of electrical current flowing
between scanning tip and surface of particles. In the case of
AFM, the force exerted on the nanoprobe as it moves along
the surface is measured electronically.

77. Microscopes
Optical Microscope
Scanning Electron Microscope
Transmission Electron Microscope
Scanning Tunneling Microscope
Heinrich Rohrer and Gerd Binnig
The Nobel Prize in Physics 1986
Scanning Tunneling Microscope
Surface of Nickel.
Fe atoms on a Cu surface
STM

78. These examples suggest that supramolecular chemistry will be
the main tool used in the development of nanotechnology –
technology based on devices with nanoscale features – which is
predicted to revolutionize our lives in the near future.

79. Nano Machines

80. Molecular Machines

81. Binding of ion A to the host
induces the binding of ion B

82. Supramolecular chemistry - Applications
Phase transfer agents
Drug delivery
Separation of mixtures
Molecular sensors
Swithces and molecular machinery
Catalysts

83. Supramolecular chemistry - Applications
Phase transfer agents
Drug delivery
Separation of mixtures
Molecular sensors
Swithces and molecular machinery
Catalysts

84. Separation of mixtures
Supramolecular chemistry - Applications

85. Phase transfer agents
Drug delivery
Separation of mixtures
Molecular sensors
Swithces and molecular machinery
Catalysts
Supramolecular chemistry - Applications

86. Phase transfer agents
Drug delivery
Separation of mixtures
Molecular sensors
Swithces and molecular machinery
Catalysts
Supramolecular chemistry - Applications

87. Supramolecular chemistry - Applications
Phase transfer agents
Drug delivery
Separation of mixtures
Molecular sensors
molecular Swithces and
Catalysts

88. Supramolecular
photochemistry
Photochemistry is the branch of chemistry
concerned mainly with the chemical effect induced
by radiations lying in the UV and visible region .

89. Scheme for photochemical supramolecule
The important parts are..
I. receptor
II. Spacer
III. Signaling unit
IV. substrate

90. Crown- anthracene system
- a fluorescent sensor
system
i) Receptor (Host) : crown ether,ii) Substrate (Guest) : K+,
iii) Signalling unit : anthracene iv) Spacer : –CH2-.

91. Supramolecular devices
These are molecules or assemblies that can
perform functions such as linear or rotational
movement, switching and entrapment. These
devices exist at the boundary between
Supramolecular chemistry and nanotechnology
and prototypes have been demonstrated using
Supramolecular concept.

92. Mainly they are classified in to
1)Molecular photonic devices : In these molecular
recognition can be used to control light emission from
molecules. These are photoactive supramolecules.
2) Molecular electronic devices : These includes
molecular wires and switches.

93. Dimer naphthalene formation
results in stronger emission
Inclusion of a guest inside the
cavity of a cyclodextrin induces
light emission
Light emission upon the binding
of a potassium ion to a crown
ether
(Photon-induced Electron
Transfer).
1) Molecular photonic devices :

94. 2) Molecular electronic devices :
These includes molecular wires and switches.
Molecular wires
Molecular wire in a lipid bilayer
electron flow across the bilayer membrane.

95. SWITCHING DEVICES
Electrical switch is used for regulating electron flow
(current). Certain supramolecules mimics this
electric switch are known as Molecular Switches.
There are mainly two kinds of molecular switches,
1)photoregulated molecular switch
2) chemically controlled molecular switch.

96. Photoregulated molecular switches
cis (on) trans (off)
a photosensitive azobenzene part at its center with
crown ethers on both sides.
Photo-induced Molecular switch causing guest binding

97. Other eg for photo-induced switch is Molecular Rectifier. A
rectifier is a device that allows only one way flow of electrons.
The switching ability is highly reversible by alternating irradiation
by UV and visible light.
OFF ON
mimics an electrical switch. When it is cyclized, a fully conjugated
path through the molecule becomes available, and is turned ON.

98. Chemically controlled molecular switch
disulfide formation decreases guest binding ability because it
blocks guest insertion
Since the thiol groups only exist inside the cavity, intermolecular
disulfide formation is also suppressed
Electron driven (chemically controlled) Molecular switch

99. OO
O
O
SS
O
O
OO
O
O
O
O
SH SH
r e d u c t i o n
o x i d a t i o n
ON (I) (II) OFF
Compound I can bind ions but (II) can not. i.e. (I) on reduction
loses the binding property.
These interconversion, ie. OF-ON mechanism is done by
reduction and oxidation of these compounds.
chemically controlled Molecular switch

100. T
H
A
N
K
Y
O
U