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1 INTRODUCTION AND CONCEPTS

WHAT IS SUPRAMOLECULAR CHEMISTRY?

DEVELOPMENT OF SUPRAMOLECULAR CHEMISTRY
HOST-GUEST CHEMISTRY
SOME BASIC CONCEPTS
WEAK INTERACTIONS
DESIGNING SUPRAMOLECULAR HOSTS

WHAT IS SUPRAMOLECULAR CHEMISTRY?

"Supramolecular chemistry is the chemistry of the intermolecular bond, covering the
structures and functions of the entities formed by the association of two or more
chemical species"
J.-M. Lehn
"In contrast to molecular chemistry, which is predominantly based upon the covalent
bonding of atoms, supramolecular chemistry is based upon intermolecular
interactions, i.e. on the association of two or more building blocks, which are held
together by intermolecular bonds"
F. Vgtle
"Supramolecular chemistry is defined as chemistry "beyond the molecule", as
chemistry of tailor-shaped intermolecular interaction. In 'supramolecules' information
is stored in the form of structural peculiarities. Moreover, not only the combined
action of molecules is called supramolecular, but also the combined action of
characteristic parts of one and the same molecule."
F. Vgtle

supra (Latin) = above, beyond...

One of the most popular and fastest growing areas of experimental chemistry
Interdisciplinary field
One field is host-guest chemistry

Host selectively binds a particular guest in order to produce a host/guest complex, a

supramolecule.
SUPRAMOLECULAR COMPOUND:
A molecular assembly where two or more compounds interact with each other via
various weak intermolecular interactions such as H-bonding, cation-, -,
CH-interactions, hydrophobic effects etc., showing inclusion, selectivity or other
functionality.

SUPRAMOLECULAR COORDINATION COMPOUND:

A Supramolecular compound where the selectivity or other functionality is achieved
via metal ion coordination.

SUPRAMOLECULAR ASSEMBLY:
A molecular assembly where two or more compounds interact with each other via
various intermolecular interactions such as metal coordination, H-bonding,
cation -, -, CH -interactions etc., resulting in large entity "a
supermolecule".

Some of the first supramolecules (at that time, these were not called
supramolecules)

a) Curtis 1961:
First Schiffs base macrocycle from
asetone and ethylene diamine

b) Busch 1964:
Schiffs base macrocycle

c) Jger 1964:
Schiffs base macrocycle

d) Pedersen 1967:
Crown ethers

References:
J.W. Steed, J.L. Atwood, Supramolecular chemistry, p.4-5, Wiley, (2000).

HOST-GUEST CHEMISTRY

A molecule (host) can bind another molecule (guest) to produce a hostguest complex
Interactions between host and guest are noncovalent
Guest may be
o a monoatomic cation
o a simple inorganic anion
o a more sophisticated molecule such as a hormone, pheromone or
neurotransmitter
Host possesses convergent binding site

Guest possesses divergent binding site

References:
J.W. Steed, J.L. Atwood, Supramolecular chemistry, p.3-4, Wiley, (2000).

CLASSIFICATION OF SUPRAMOLECULAR HOST-GUEST COMPOUNDS

Division into two major classes according to type of the host-guest aggregate:
a) Cavitand = host with intramolecular cavities host-guest aggregate is
cavitate
b) Clathrand = host with extramolecular cavities, host-guest aggregate is
clathrate

After F. Vgtle, Angew. Chem., Int. Ed. Engl., 1985, 24, 728

Further these can be divided by the forces between the host and the guest:

When the forces are electrostatic the host-guest system is a complex

When the forces are nondirectional, less specific such as hydrophobic, van der
Waals or crystal close-packing effects, then the names used are cavitate and
clathrate
Division relating to the stability of a host-guest complex in solution:
o Clathrate-hosts (such as gas hydrates and urea clathrates) are stable
only in the solid state
o Cation- and anion-binding hosts (such as crown ethers, cryptands and
spherands) and hosts for neutral molecules are stable both in solid
state and in solution , sometimes also in the gas-phase
o There also exists purely liquid-phase phenomena: liquid crystals and
liquid clathrates

References:
J.W. Steed, J.L. Atwood, Supramolecular chemistry, p. 6-7, Wiley, (2000).

SOME BASIC CONCEPTS

RECEPTORS, COORDINATING AND THE LOCK-AND-KEY PRINCIPLE

Selective binding must involve attraction or mutual affinity between host and
guest
-> theory of coordination chemistry by Alfred Werner in 1893
Enzyme (host) has a binding site to witch its substrate (guest) fits (like a
glove in the hand)
The guest has a geometric size or shape complementary to the receptor
(host)
-> lock and key principle by Emil Fischer in 1894
Paul Ehrlich in 1906: molecules do not act if they do not bind
-> the concept of a biological receptor

CHELATE- AND MACROCYCLIC EFFECTS

The interaction of the whole system is synergically greater than the sum of
the parts
Such extra stabilization has its basis in the chelate and macrocyclic effects
Metal complexes of bidental ligands are significantly more stable than closely
related materials that contain unidentate ligands
Stabilization via chelate effect in solution is due to both thermodynamic and
kinetic effects
The stabilization offered by the chelate effect is highly dependent on the size
of the chelate ring
The chelate effect can be used to stabilize the system

a) Chelate effect (Blue pentagon represents a donor)

When the host-guest system is even more stabile than would be expected
from the chelate effect alone, there usually are also macrocyclic effects
present
The host of these species is usually macrocyclic
The macrocyclic effect relates not only to the chelation of the guest by
multiple binding sites but also to the organization of those sites in space
Macrocyclic effect was first introduced by Cabbines and Margerum in 1970
Macrocyclic effect has both enthalpic and entropic contributions

b) Chelate and macrocyclic effects

Bicyclic hosts such as cryptands are found to be even more stable than
monocyclic corands because of the macrobicyclic effect

c) Chelate and macrobicyclic effects

(a), b) and c) after J.W. Steed and J.L. Atwood in Supramolecular Chemistry,
(2000))
References:
J.W. Steed, J.L. Atwood, Supramolecular chemistry, p.9-13, Wiley, (2000).

PREORGANIZATION AND COMPLEMENTARITY

In order to bind, a host must have binding sites that are of the correct
electronic character to complement those of the guest
Those binding sites must also sterically match to the conformation of the
binding site of the guest
The host that fulfils these criteria is said to be complementary

If the host molecule does not undergo any significant changes in conformation
when binding the guest it is said to be preorganised

A good example of a preorganized host is spherand which is well preorganized

in order to bind alkali metal cations

References:
J.W. Steed, J.L. Atwood, Supramolecular chemistry, p.13-14, Wiley, (2000).

WEAK INTERACTIONS (SUPRAMOLECULAR INTERACTIONS)

Supramolecular chemistry is the chemistry of weak interactions, i.e.

noncovalent intermolecular forces
Categories:
o (Ion-ion interactions) (Strongest)
o Ion-dipole interactions
o Dipole-dipole interactions
o Hydrogen bonding
o Interactions involving p-systems
o Van der Waals forces
o Close packing
o Hydrophobic effects (Weakest)
Classification is not unambiguous

ION-ION INTERACTIONS 100-350 KJ/MOL

Comparable in strength to covalent bonding -> is it really a weak interaction?

Examples

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ION-DIPOLE INTERACTIONS 50-200 KJ/MOL

Ion interacts with a polar part of a molecule

Typical examples alkali metal-crown ether complexes

Examples of ion-dipole interactions in supramolecules. N.B.! Notations for complexes.

Coordinative (dative) bonds between nonpolarisable metal cations and hard

bases: Lewis base (ligand) and Lewis acid (metal) are attached by means of
lone-pair electrons
Coordinative bond has a significant covalent component
Strong, which causes the structures to be stabile, but yet kinetically labile
allowing reorganisation
Well-defined geometries (coordination number of metals) -> useful in crystal
engineering and synthesis
o coordination numbers vary from 2 to 8 (usually 2 or 6)
Formation of coordinative bonds requires some level of complementarity
(conformational and stereoelectronic, size)
Examples [Ru(BiPy)3]2+ and grid-type of supramolecular assemblies

DIPOLE-DIPOLE INTERACTIONS 5-50 KJ/MOL

Typical with organic carbonyl compounds

HYDROGEN BONDING 4-120 KJ/MOL

VERY IMPORTANT!
May be considered as particular kind of dipole-dipole interaction
Directional, electrostatic, certain geometry
Donor is partially positive hydrogen: partial charge arises from the large
difference in electronegativity of hydrogen and the atom to which it is
attached (typically O, N, S, F, (C)) -> highly polarised covalent bond
Acceptor is (partially) negative atom with unshared valence electrons or
polarisable -electrons
Formation of hydrogen bonds causes a singnificant decrease in energy -> in
solid state as many H-bond as possible are formed (keep in mind geometric
restrictions and the closest packing)
The solvent is the defining factor when forming hydrogen bonds
Very polar solvent causes hydrogen bonds to collaps
Hydrogen bonding is strongest in nonpolar/low polarity solvents

Hydrogen bonding often orders the overall shape of a biological molecule

In DNA the hydrogen bond system is sheltered by the double helix-structure
(In DNA also -interactions have effect in the maintaining of the
structure)

Hydrogen bonding has also an important role in tautomerism

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Subcategories: strong, moderate and weak hydrogen bonding

Strong H-bonds are formed when there is electron density deficiency in the
donor or an excess of electron density in the acceptor or when configuration
or conformation of the molecule forces the donor and acceptor closer than
normal H-bonding distance
Moderate bonds (most common type) form typically between neutral group
Weak H-bonds are formed when hydrogen is bonded to only slightly more
electronegative atom (C, Si) or when acceptor has -electrons instead of lonepairs or it is otherwise poor acceptor (Br, Se).
Weak H-bonds have more geometrical freedom
Donor properties of C-H depend on the hybridisation of C, the
electronegativity of the atom C is attached to, steric environment of hydrogen
and on the basicity of the acceptor
Cooperativity: although a single interaction (e.g. H-bonding) is quite weak,
several simultaneously acting interactions increase the stability significantly
-cooperativity: hydrogen bonding to continuous chains or cycles
-cooperativity (resonance-assisted H-bonding): hydrogen bonding between
molecules with conjugated multiple -bonds

Hydrogen-bonding of non-linear molecules produces non-linear H-bonded

polymers and may also result in H-bonded macrocycle
Hydrogen bonding of planar molecules with more than two H-bonding
possibilities produces H-bonded sheets
Hydrogen bonding of molecules with three-dimensionally organized H-bonding
sites can result in 3D H-bonded network/lattice

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WEAK INTERACTIONS INVOLVING -SYSTEMS

Three subcategories: D-H, and cation

Note: D-H could also be classified as weak H-bonding and the properties of
weak H-bonding apply for this interaction (e.g. directionality)
interaction (-stacking; 0-50 kJ/mol) is non-directional, electrostatic,
attractive force, which occurs when attraction between -electrons and framework overcome the unfavorable - repulsions
Most typical geometries edge-to-face (herringbone pattern) and offset faceto-face -> direct face-to-face is repulsive

Polarisation of -systems by heteroatoms may lead to direct face-to-face

geometry
Significant both in nature (e.g. DNA) and in artificial systems, but difficult to
predict and control (weakness, weak directionality)
Cation interactions (5-80 kJ/mol) occur between metallic or organic
cations and aromatic or double/triple bonded regions of the molecule
Electrostatic force, but relates also to the polarisability of the aromatics (ioninduced dipole, donor-acceptor, charge transfer or dispersion force)

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An example of cation interactions

VAN DER

WAALS FORCES (< 5 KJ/MOL)

Collective name for non-directional dispersion (London) forces weakly bonding

at long distance and exchange-repulsion forces strongly non-bonding at short
distances
Attractive dispersion forces are caused by fluctuating multipoles (polarisation
of electron cloud)
Proportional to the size of the molecule and inversely proportional to the sixth
power of distance
Repulsive forces balance the dispersion forces and define molecular shape and
geometry -> important in crystal packing
Usually term VDW-forces refers to CC, CH and HH interactions

CLOSE PACKING

Solid state phenomena -> Nature abhors vacuum

Maximisation of favourable isotropic VDW interactions
o move you mouse cursor on the picture in order to see the close packed
structure

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HYDROPHOBIC EFFECTS

Relate to the exclusion of large or weakly solvated (hydrophobic) species from

polar media
Can be devided to enthalpic and entropic components
Enthalpic effect: stabilisation of polar solvent excluded from the cavity upon
guest binding
Entropic effect: combination of host and guest results in less disruption to the
solvent structure -> entropic gain
Typical examples: Binding of organic guests by cyclodextrins or cyclophanes
in water

After J.W. Steed and J.L. Atwood in Supramolecular Chemistry, (2000).

References:
J.W. Steed, J.L. Atwood, Supramolecular chemistry, p.19-30, Wiley, (2000).

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DESIGNING SUPRAMOLECULAR HOSTS

Selectivity towards a particular guest can be achieved by using chelate and

macrocyclic effects, complementarity and host preorganisation
Definition and careful consideration of the target -> properties of the host
system
Organisation
Selection of the type and the number of binding sites
The nature of the organic framework of the host itself

SOME LINKS:
http://www.ch.kcl.ac.uk/kclchem/staff/jws/supramol/textbook.htm

Www-pages of the Supramolecular Chemistry - textbook

http://www.uni-saarland.de/fak8/schneider/supram/supramolecular_structures.html

Structures of different kinds of supramolecular compounds

http://www.infochembio.ethz.ch/links/en/chem_supramol.html

A list of links to supramolecular resources

Following are some questions on the topics you just read about. Please, take some
time to think back what youve just learned about the concepts of supramolecular
chemistry and try to answer these questions. Notice that there may be more than
one correct answer for the questions.

How would you define the concept "supramolecular chemisty"?

In your opinion, why is supramolecular chemistry so widely spread and
interdisciplinary field of science?
Why are supramolecular or weak interactions so important?
Supramolecular interactions are present in countless amount of "events" of
biological life. Can you find out some of them?