1. Supramolecular Chemistry:
General Principles, Selected Examples and Applications
Yanhua Lan
1

2. Contents
• Historical Notes
• Keywords and Definitions
• Different Types of Supramolecular Interactions
• Discipline of Self‐assembly
• Examples:
• Grids, from Ligand Design to Self‐assembly Process
• Application
2

3. 3

4. 4

5. 5

6. In the 1990s, supramolecular chemistry became even more
sophisticated, with researchers such as James Fraser Stoddart
developing molecular machinery and highly complex self‐
assembled structures, and Itamar Willner developing sensors and
methods of electronic and biological interfacing. During this
period, electrochemical and photochemical motifs became
integrated into supramolecular systems in order to increase
functionality, research into synthetic self‐replicating system
began, and work on molecular information processing devices
began. The emerging science of nanotechnology also had a
strong influence on the subject, with building blocks such as
fullerenes, nanoparticles, and dendrimers becoming involved in
synthetic systems.
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7. Keywords
Supramolecular chemistry
‐ “the chemistry beyond the molecule” or “the chemistry of the
noncovalent bond” (Lehn 1988, 1994, 1995).
‐ the molecular components are held together and organised by
means of non‐covalent binding interactions.
Metallosupramolecular chemistry
‐ The metals act as a type of “glue” to hold together assemblies
of organic molecules ‐ a term introduced by Constable in 1994.
‐ By employing donor groups in organic molecules (ligands) that
bridge more than one metal centre it is possible to construct
one‐, two‐ or three dimensional architectures, based on M‐L
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interactions.

8. Molecular Recognition
‐ Molecular recognition is the specific interaction between two
molecules, which are complementary in their geometric and
electronic features (like two fitting pieces of a jigsaw puzzle).
‐ The classical lock and key principle describes the interaction of
components due to their shape and rigidity (preorganization).
Self‐assembly
‐ Recognition between molecules leads to an aggregation, which
finally results in an ensemble that is composed of two or more
discrete units (Philp and Stoddart 1996; Lawrence et al. 1995).
‐ mixing of the components spontaneously affords only one well‐
defined product.
‐ Strict self‐assembly: directly proceeds toward the formation of a well‐
defined aggregate.
‐ Directed (templated) self‐assembly: controlled/influenced by some
additional species, e.g., templates (Lindsey 1991). This means, in an
idealized case self‐assembly follows a “cooperative” or allosteric process.
‐‐‐ thermodynamically most stable species. 8

9. 9

10. Supermolecules vs. Supramoleular Assemblies
Supermolecules Supermolecular Assemblies
• well‐defined, discrete species formed • polymolecular entities from
from a defined, finite number of spontaneous, but defined association of
molecules many molecules
• the equivalent of low molecular weight • the equivalent of high molecular
organic molecules weight polymers and macromolecules
• host‐guest chemistry • supramolecular self‐assembly
• individual non‐covalent interactions may be weak, but
many of them will still yield “stable” structures while
allowing for “self‐healing” (error correction).
J.‐M. Lehn, Pure Appl. Chem. 1978, 50, 871.
G.M. Whitesides, Science 2002, 295, 2418; 10
Proc. Natl. Acad. Sci. USA 2002, 99, 4769

11. Supramolecular interactions (Noncovalent interactions) might be
roughly classified in the following categories:
Markus Albrecht, Naturwissenschaften, 2007, 94:951‐966.
Jonathan W. Steed, David R. Turner, Karl J. Wallace, Core Concepts in 11
Supramolecular Chemistry and Nanochemistry, John Wiley & Sons, Ltd, 2007

12. • Ion‐Ion Interactions:
• Strong (200‐300 KJ/mol)
• Ion–ion interactions are non‐directional in nature, meaning
that the interaction can occur in any orientation.
Tetrabutylammonium chloride
For example: Acid‐base pairs in particular in proteins
12

13. • Ion‐Dipole Interactions:
• Moderately strong (50‐200 KJ/mol);
• Stronger when partially covalent (100‐400 KJ/mol)
sodium complex of crown‐5
Cation binding hosts
metal complexes (partially covalent)
13

14. • Dipole‐Dipole Interactions
• Relatively weak (5‐50 KJ/mol)
• Despite being the weakest directional interaction, dipole–dipole interactions are
useful for bringing species into alignment, as the interaction requires a specific
orientation of both entities.
dipole–dipole interactions in acetone; dipole moment 2.91D
14

15. Electrostatic interactions are caused by the attraction (Coulombic)
between opposite charges / differently charged ions or dipoles.
• Ion–ion interactions are non‐directional in nature, meaning
that the interaction can occur in any orientation.
• Ion–dipole and dipole–dipole interactions, however, have
orientation‐dependant aspects requiring two entities to be
aligned such that the interactions are in the optimal direction.
Electrostatic interactions play an important role in understanding the factors
that influence high binding affinities, particularly in biological systems in
which there is a large number of recognition processes that involve charge–
charge interactions; indeed these are often the first interactions between a
substrate and an enzyme.
15

16. • Hydrogen bonding (I)
‐ Hydrogen bond donors are groups with a hydrogen atom attached to an
electronegative atom (such as nitrogen or oxygen), therefore forming a dipole
with the hydrogen atom carrying a small positive charge.
‐ Hydrogen bond acceptors are dipoles with electron‐withdrawing atoms by which
the positively charge hydrogen atom can interact, for example, carbonyl moieties.
A carbonyl accepting a hydrogen bond from a secondary amine donor (a) and (b) the
standard way of expressing donor and acceptor atoms (D, donor atom; A, acceptor atom).
16

17. • Hydrogen bonding (II)
Various types of hydrogen bonding geometries: (a) linear; (b) bent; (c)
donating bifurcated; (d) accepting bifurcated; (e) trifurcated; (f) three‐
centre bifurcated.
17

18. • Hydrogen bonding (III)
‐ the most important non‐covalent interaction in the design of supramolecular
architectures, because of its strength and high degree of directionality. It
represents a special kind of dipole–dipole interaction between a proton donor
(D) and a proton acceptor (A).
18

19. 19

20. Multiple Hydrogen‐Bonding Sites in DNA Base Pairs
• complementary arrangements of hydrogen‐bond acceptors/donors for selective
binding
• mutually enforcing donors and acceptors
(a) Primary and secondary hydrogen bond interactions
between guanine and cytosine base‐pairs in DNA
20
(b) And a schematic representation.

21. 21

22. 22

23. • . π− Interactions
(i) cation–π interactions ‐ relatively weak (5‐80 KJ/mol)
alkaline‐ and alkaline‐earth metals also form interactions with double‐bond
systems. For example, the interaction of potassium ions with benzene has a
similar energy to the K+ –OH2 interaction.
bis(benzene)chromium
‐ covalent (no charges)
ferrocene
‐mainly covalent
23

24. and (ii) π–π interactions
Weak (5‐50 KJ/mol)
The two types of – interactions:
(a) face‐to‐face; (b) edge‐to‐face.
24

25. (a) Top and (b) side views of the layered structure of graphite, held
together by face-to-face -interactions.
The layered structure of graphite is held together by weak, face‐to‐
face ‐interactions and therefore feels ‘slippery’. It is because of the
slippage between layers that graphite can be used as a lubricant
(albeit in the presence of oxygen).
Interactions involving π‐systems can be found in nature, for example, the
weak face‐to‐face interactions between base‐pairs along the length of the
double helix are responsible for the shape of DNA.
25

26. • van der Waals interactions
(mutually induced dipoles)
• Weak (2‐20 KJ/mol)
• Dispersion effects: London interaction and the exchange and repulsion
interaction
• van der Waals interactions arise from fluctuations of the electron
distribution between species that are in close proximity to one another.
A London interaction between two argon atoms. The shift
of the electron cloud around the nucleus produces
instantaneous dipoles that attract each other 26

27. • van der Waals interactions
27

28. • Hydrophobic effects
• Hydrophobic effects arise from the exclusion of non‐polar groups or
molecules from aqueous solution. This situation is more energetically
favourable because water molecules interact with themselves or with
other polar groups or molecules preferentially.
Two organic molecules creating a hole within an aqueous
phase, giving rise to the entropic hydrophobic effect –
one hole is more stable than two.
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29. • Hydrophobic effects
‐ enthalpic hydrophobic effect
29

30. Projection of a chain within the structure of [Ni2(cis‐chdc)2(dpa)2] showing the π‐π
overlap of the pyridine in dpa and the hydrogen bonds (dotted) between H of dpa
(di‐2‐pyridylamine) and O of cis‐chdc (1,4‐cyclohexanedicarboxylate)
30
Kumagai, Crystal Growth & Design, 9(6), 2009, 2734‐2741.

31. Multivalency and Cooperativity
Multivalency is the binding of two or more entities that involves the simultaneous
interaction between multiple, complementary functionalities on these entities.
The fact that the resulting binding constant (i.e., binding energy) is often higher
than expected from its individual components is known as cooperativity.
A. Mulder, J. Huskens, D. N. Reinhoudt, Org. Biomol. Chem. 2004, 2, 3409 31

32. Discipline of Self‐assembly
Two common types of building blocks for
perpendicular coordination arrangements
bidentate binding pocket tetrahedral metal ion
terdentate binding pocket octahedral metal ion
32

33. 33

34. Self‐assemled Architectures:
Ladders, Lattices, Polygons, Grids, Helicates, Rotaxanes, Catenanes,
Knots, Cages, Cubes, Capsules ……
Trinuclear double helicate
M. Fujita,
P. Stang,
J. Lehn,
J. –P, Sauvage,
E. Constable 34

35. Ligand design
Diazines as bridging ligands
6 4 6 N 2
6 3
N N N N
5 N 3
35

36. - Grids
• Grids involve a set of parallel ligand components
held more or less orthogonally to another set of
parallel ligand components with metal ions at
the crossing points.
4 + 4 [2 x 2]
6 + 9 [3 x 3]
36

37. ‐ Pyridazine‐containing grids
Bis‐bidentate ligand
[CuI4(I)4](CF3SO3)4
N N N N
I
Youinou M.‐T., Rahmouni N., Fischer J., Osborn J. A., Angew. Chem. Int. Ed. 37
Engl., 1992, 31, 733.

38. 8+
N N
NH NH
4+ NH N N M NH
N M
N
H H Ph
N N N N
N N N Ph Ph
N
M M
Ph Ph N N
N N N N NH
N N NH
M M
H H N NH N N NH
N N N
Ph
38
Y. Lan, PhD thesis, University of Otago, Dunedin, New Zealand

39. Self‐assembly of tetranuclear [2x2] grid complexes of (L7)2‐
(metal:ligand:base = 4:4:8)
0
N O NO
N
N N
N N N
NH N
N Ph N
O
N O N O N
4 4 (BF4)2.xH2O Ph Ph
Ph
N 8 TEA N NO
O
O N N
N N N
NH O N
N Ph O N
N N N
H2L7 = M (Zn, Cu, Ni, Co)
[ZnII4(L7)4]∙3H2O
[CuII4(L7)4]∙3H2O
[NiII4(L7)4]∙6H2O
[Co4(L7)4](BF4)0.25∙11H2O∙2CH3OH
39
Y. Lan, PhD thesis, University of Otago, Dunedin, New Zealand

40. [CoII4(III)4](BF4)8
Bis‐terdentate ligand
H H
N N
N N
N N N N
III
Ruben M., Lehn, J.‐M., Vaughan G., Chem. Commun., 2003, 1338. 40

41. Molecular Switch
Electrochemical properties of [CoII4(II)4](BF4)8
N N
N N N N
Ph
II
• Ten well‐resolved reversible
reduction steps involving
eleven electrons at ‐20oC;
• The first example of the
highest reported number of
electron transfer steps for a
molecular compound.
Ruben M., Breuning E., Gisselbrecht J. P., Lehn J.‐M., Angew. Chem. Int. 41
Ed., 2000, 39, 4139.

42. Optical properties of [CoII4(III)4](BF4)8
• Optical switching, with
intense reversible colour
changes (pale yellow at
low pH to orange and
finally deep violet above
neutral pH).
Colour change at different pH
42
Ruben M., Lehn J.‐M., Vaughan G., Chem. Commun., 2003, 1338.

43. Gas, Solvent Storages; Gas Separation
• The unsaturated Cu2+ sites were observed
to bind D2 at increased D2 loading
• Crystal structure of Cu3(btc)2 and the
position of the Cu2+‐bound D2 molecules
(yellow spheres) as determined by powder
neutron diffraction. Green, red, and gray
spheres represent Cu, O, and C atoms,
respectively.
• Infrared stretching band at 4100 cm‐1,
characteristic of metal–H2 interactions.
• Zero‐coverage H2 binding enthalpy is
increased.
• H2 adsorption capacity shows H2 uptake.
J. Long, Angew. Chem. Int. Ed. 2008, 47, 6766 – 6779; 43
Batten, Angew. Chem. Int. Ed. 2009, 48, 8919 –8922

44. Supramolecular magnetic materials:
{CuLn} unit:
Ln = Tb
a)
right - ∆. left- Λ
3 {CuLn} units
linked through Right- and left-
trimesic acid: handed
Ln = Dy propellers
interweave to
b) Λ∆ d) give the full
[{CuDy}3]2 motif
The 3-bladed
propeller motif of
{CuDy}3
c) e)
Supramolecular “Double‐Propeller” Dimers of Hexanuclear CuII/LnIII Complexes: A {Cu3Dy3}2 Single‐Molecule
Magnet, G. Novitchi, W. Wernsdorfer, L. F. Chibotaru, J. –P. Costes, C. E. Anson, A. K. Powell, Angew. Chem. 44
Int. Ed., 2009, 48, 1614‐1619.

45. Magnetic behaviour for {CuDy} and [{CuDy}3]2
Hysteresis for
{CuDy} (field
dependence at
M/Ms
different
frequencies).
What is the origin of the dramatic
enhancement of SMM properties
in forming the dodecanuclear
supramolecular complex?
Hysteresis for
[{CuDy}3]2
(field
Answer seems to
dependence M/Ms lie with the
at different
imposed
frequencies).
arrangement of the
Dy centres.
Bulk susceptibility studies show very small Cu-Dy coupling, as expected.
45

46. Guest Tunable Structure and Spin Crossover Properties
SCOF‐2 is [Fe(NCS)2(bpbd)2] and bpbd is 2,3‐bis(4′‐pyridyl)‐2,3‐butanediol
(a) Interpenetrating grid structure of SCOF‐2(guest)
(b) square 1‐D pores where guest molecules reside.
C.J. Kepert, J. AM. CHEM. SOC. 2009, 131, 12106–12108 46

47. C.J. Kepert, J. AM. CHEM. SOC. 2009, 131, 12106–12108 47

48. (SCOF‐2(Acn) (red), SCOF‐2(Ac) (orange)) and the protic (SCOF‐2(Me) (blue), SCOF‐
2(Et) (purple), SCOF‐2(Pr) (green), where guest) = acetonitrile (Acn), acetone (Ac),
methanol (Me), ethanol (Et), and 1‐propanol (Pr).
C.J. Kepert, J. AM. CHEM. SOC. 2009, 131, 12106–12108 48