SMC 003

Supramolecular Interactions
Dushyant B. Varshey, John R. G. Sander, Tomislav Frisc ic,

and Leonard R. MacGillivray
University of Iowa, Iowa City, IA, USA
1
2
3
4
5
6
7
8
Introduction
Supramolecular Chemistry
Supramolecular Interactions
Construction of Supramolecular Compounds
HostGuest Chemistry
Molecular Recognition
Self-Assembly
Supramolecular Structures via Molecular
Recognition and Self-Assembly
9 Conclusions
References
9
9
10
16
16
16
16
17
21
21
INTRODUCTION
To achieve the impeccable ability of nature to construct

molecules (e.g., proteins), chemists have traditionally
employed approaches at the molecular level. Molecular chemistry, since the synthesis of urea by Wohler in
1828,1 has relied on building molecules via stepwise formation and breakage of covalent bonds. Molecular techniques of chemists have culminated into the total syntheses
of sophisticated molecules (e.g., vitamin B12).2 However, nature routinely utilizes noncovalent interactions to
organize molecules to form aggregates that perform specific functions. Chemists now recognize advantages of
the synthesis paradigm of biology that can facilitate the
construction of complex molecules, otherwise unavailable

via traditional approaches. An early transition toward this
approach was realized when Emil Fischer, in 1894, proposed the lock-and-key model for enzymesubstrate
interactions.3 The elegant mechanisms of enzymes provided
basic principles for the new subject, namely, Supramolecular Chemistry, from which principles of molecular recognition and supramolecular function evolved.4, 5
SUPRAMOLECULAR CHEMISTRY
The term supramolecular chemistry was coined by JeanMarie Lehn in 1969. Lehn defined supramolecular chemistry as the chemistry of molecular assemblies and intermolecular bonds, which is more commonly referred to the
chemistry beyond the molecule.6 The Nobel Prize was
awarded to Lehn, Charles Pedersen, and Donald Cram in
1987 for pioneering contributions to supramolecular chemistry.7 As molecules are built by connecting atoms by
covalent bonds, supramolecular compounds are built by
linking molecules with intermolecular forces (Figure 1).8
Thus, in molecular chemistry, precursor molecules undergo
covalent-bond making or breaking to produce a target
molecule A. In contrast, in supramolecular chemistry
molecule A can act as a host that interacts with a guest
via noncovalent forces (e.g., hydrogen bonds) to form a
supermolecule B.
2.1
Development of supramolecular chemistry
The concepts and roots of supramolecular chemistry can

be traced to the discovery of chloride hydrate by Sir
Supramolecular Chemistry: From Molecules to Nanomaterials, Online 2012 John Wiley & Sons, Ltd.
This article is 2012 John Wiley & Sons, Ltd.
This article was published in the Supramolecular Chemistry: From Molecules to Nanomaterials in 2012 by John Wiley & Sons, Ltd.
DOI: 10.1002/9780470661345.smc003
Concepts
Pedersen (1967),14 which were compared to natural macrocycles (e.g., ionophores, heme). Seminal contributions were
then made by Pedersen and Lehn on crown ethers and
cryptands (1960s),7 respectively, and Cram on spherands
(1970s) (Figure 2).15 Moreover, the development of synthetic receptors introduced molecular recognition as an
area that blossomed into supramolecular chemistry by
collaborative concepts that stemmed from biology and
physics. Supramolecular chemistry is now a major interdisciplinary field that embodies the expertise of synthetic
organic chemists, inorganic, and solid-state chemists, theorists, physicists, and biologists that strive to develop
new molecules and materials with unique properties and
applications.
Molecular chemistry
Molecular precursors
A
Supramolecular chemistry
A
Host
Guest
B
Figure 1 An illustration of molecular versus supramolecular

chemistry.
SUPRAMOLECULAR INTERACTIONS
Supramolecular compounds are formed by additive and

cooperative noncovalent interactions. The noncovalent
interactions include a wide range of attractive and repulsive forces. The most common noncovalent interactions,
along with approximate energies, are listed in Table 1.8 A
detailed understanding of the origins and scopes, as well
Humphrey Davy in 1810.8, 9 Development was initiated

through the understanding of selective binding of alkalimetal cations by natural,10 as well as synthetic, macrocyclic, and macropolycyclic ligands1117 as described by
Curtis (1961),11 Busch (1964),12 Jager (1964),13 and
H3C
O
O
H3C
N
O
O O
CH3
H 3C
O
H3C
O O
CH3
O
CH3
O
H 3C
CH3
CH3
H3C
(a)
Figure 2
Table 1
(b)
(c)
CH3
Early developments in supramolecular chemistry: (a) crown ether (Pedersen) (b) cryptand (Lehn) (c) spherands (Cram).
Common supramolecular interactions.8
Supramolecular interactions
Directionality
Ionion
van der Waals
Closed-shell metalmetal
Iondipole
Dipoledipole
Coordination bonds
Hydrogen bonds
Halogen bonds
interactions
Cation and anion interactions
Nondirectional
Nondirectional
Nondirectional
Slightly directional
Slightly directional
Directional
Directional
Directional
Directional
Directional
Bond energies (kJ mol1 )

100350
<5
560
50200
550
100300
4120
1050
250
580
Examples
NaCl
Inclusion compounds
Argentophilic (Ag Ag)
Na+ crown ether complex
CN groups
M-pyridine
Carboxylic acid dimer
Sulfuriodine complex
Benzene (edge-to-face) DNA (face-to-face)
+
N(CH3 )4 (toluene)
DOI: 10.1002/9780470661345.smc003
as the interplay, of such interactions is a major goal of

researchers worldwide.
K
3.1
Directional versus nondirectional
Supramolecular interactions are used to construct assemblies of molecules and/or ions that exhibit specific properties and functions. Directional forces are particularly useful
since geometric and spatial control of interacting species
can be optimized.8, 1820 Nondirectional forces, however,
can be important in determining relative distances of interacting partners and, when integrated with covalent bonds,
can influence the orientations of partners in an assembly
process.8, 1820
3.2
Ionion and van der Waals
Ionion and van der Waals forces lie at extremes in

terms of strength, with both being nondirectional. Protypical
examples of materials sustained by ionion interactions
are the crystal structures of simple inorganic salts. The
electrostatic attraction between the cation and anion is often
manifested in an isotropic lattice (e.g., NaCl), reflecting the
nondirectional nature of the ionic forces. The integration of
formal positive and negative charges into molecular species
(e.g., macrocycle), however, can achieve directional control
of supramolecular association via ionion interactions
(e.g., hostguest systems) (Figure 3).2123 van der Waals
interactions arise from the polarization of an electron cloud
by the proximity of an adjacent nucleus.24 Molecules
considered soft exhibit the most pronounced van der
Waals interactions, which will particularly be important in
a condensed phase (e.g., solid state) where solvent effects
are eliminated.18
Fe
Figure 4 X-ray crystal structure of K+ encapsulated by

dibenzo-18-crown-6 (anion omitted for clarity).26
3.3
Iondipole and dipoledipole interactions result from

an electrostatic attraction between an ion and a neutral
molecule with a dipole or two molecules with dipoles,
respectively. The interactions are intermediate to weak in
strength. The solvation of metal cations (e.g., hydration)
is dictated by iondipole interactions, while interactions
between highly polar molecules (e.g., nitriles) are dictated by dipoledipole interactions (Figure 4).26 Although
the interactions are predominantly based on electrostatics, a degree of directionality arises from the anisotropic
nature of the polar molecules. Dipoledipole interactions
can influence bulk physical properties (e.g., boiling point)
and, owing to relative weakness, will often give rise to
multiple spatial arrangements and geometries of interacting
molecules.
3.4
Closed-shell metalmetal interactions
Interactions between closed-shell metal cations of d8 -d10 -s2

systems (e.g., Ag(I)) are significant contributors to stabilizing the assembly of inorganic, organometallic, and metalorganic subunits.27 The interactions are weaker in strength
than ionic and covalent bonds yet comparable to hydrogen
bonds.27 Prominent examples include interactions of Ag(I)
and Au(I) ions in the form of agentophilic and aurophilic
forces respectively (Figure 5).28, 29 The interactions can be
present in ligand-supported and ligand-unsupported environments. van der Waals interactions involving ligands can,
thus, impart directionality of an assembly process based on
closed-shell forces.
3.5
Figure 3 X-ray crystal structure example of ionion interactions demonstrated by the interaction of ammonium with
Fe(CN)6 3 .25
Iondipole and dipoledipole interactions
Coordination bonds
While the structural manifestations of coordination bonds

find deep roots as discussed in the the work of Werner30, 31
involving transitionmetalion complexes, coordination bonds have found found widespread application in
supramolecular chemistry.3234 Coordination bonds are of
DOI: 10.1002/9780470661345.smc003
Concepts
Ag
Au
F
(a)
(b)
Figure 5 Agentophilic and aurophilic interactions in crystalline: (a) dinuclear

(phenyl)ethylene)4 ][CO2 CF3 ]2 and (b) [2]rotaxane with a Au(P(CH3 )3 )2 + rod.28, 29
intermediate strength and, similar to hydrogen bonds,

reversible. The selection of an inert or labile coordination
bond is crucial to the assembly of supramolecular structures as the dynamic nature of the latter allows the components of a supramolecular structure to undergo a series
of error corrections until the thermodynamically favored
product is achieved. Once a stable structure is obtained, the
labile coordination bonds are capable of showing remarkable cooperativity to impart enhanced ligand stability.35
Coordination bonds also offer the panoply of tools supplied by the field of inorganic chemistry (e.g., coordination
number, chelation) to import function into supramolecular structures. Consequently, coordination bonds offer a
unique and attractive means to modify the properties of
supramolecular structures and materials via both metal
ions and ligands (e.g., magnetism, optical).3641 Geometric parameters that define coordination bonds as derived
from the field of inorganic chemistry are well documented.42
3.6
Hydrogen bonds
The hydrogen bond, owing to a relatively strong and highly

directional nature, is often described as the master-key
anisotropic interaction.43 The first description of a hydrogen
bond was provided by Linus Pauling in 193144 in a paper
describing the nature of the chemical bond. The term
addressed the incorrect assignment of a hydrogen bond
within the [H : F : H] ion. Pauling defined the hydrogen
bond as a bond formed when the electronegativity of A
relative to H in an AH covalent bond is such that it can
withdraw electrons and leave protons partially unshielded.45
To interact with the donor AH bond, the acceptor B
must possess a lone pair of electrons or polarizable
electrons. In general, a hydrogen bond can be represented
as AH B, where a hydrogen atom acts as a bridge
between two atoms A and B. A prototypical example that
also illustrates structural consequences of hydrogen bonds is
the carboxylic acid dimer, which is sustained by two OH
O forces (Figure 6a). Hydrogen bonds are ubiquitous in
complex
[Ag2 (trans-1-(4-pyridyl)-2-
H
Backbone
O H
R
O
H O
Carboxylic acid
(a)
N H
Backbone
N H
Guanine
(b)
H N
H
H
Cytosine
Figure 6 Hydrogen bonding: (a) carboxylic acid dimer and

(b) DNA base pairing.
nature, dictating the recognition of substrates by enzymes

and being responsible for maintaining the double-helical
structure of DNA (Figure 6b). The International Union
of Pure and Applied Chemistry (IUPAC) has recently
established the hydrogen bond as an attractive interaction
between a hydrogen atom from a molecule or a molecular
fragment XH in which X is more electronegative than
H, and an atom or a group of atoms in the same or a
different molecule, in which there is evidence of bond
formation.46
Hydrogen bonds can have different lengths, strengths,
and geometries (Table 2).8, 16, 43, 47 A strong hydrogen bond
can resemble a covalent bond with respect to the energy
required to break the interaction, while the energy of a
weak hydrogen bond will be closer to a van der Waals
force. Desiraju has described three extremes of hydrogen
bonds in the solid state. In the AH B hydrogen bond,
when both A and B are quite electronegative; for example,
NH O, the hydrogen bond is considered to be strong
or conventional (2040 kJ mol1 ).16, 47 On the contrary,
if both A and B are moderate to weakly electronegative,
for example, CH O, the hydrogen bond is weak or
nonconventional (220 kJ mol1 ).
The strength of a hydrogen bond can reach a mostly
covalent level as in the HF2 ion (170 kJ mol1 ). Hydrogen bonds involving interactions of NH, OH, and
CH groups with double and triple bonds in the form
of C=C and CC bonds, respectively, as well as aromatics, have also become important for understanding
DOI: 10.1002/9780470661345.smc003
Table 2
Properties of hydrogen bonds.8, 16, 43

Strong
AH B
Energy
Lengths (A)
H B
A B
Angles ( )
Examples
Partially covalent
60120 kJ mol1
AH H B
1.21.5
2.22.5
175180
Strong acids/bases;
proton sponge; HF
complexes
Moderate
Mostly electrostatic
1660 kJ mol1
AH < H B
1.52.2
2.53.2
130180
Acids; alcohols;
biological molecules
Weak
Electrostatic
<12 kJ mol1
AH H B
2.23.2
3.24.0
90150
Minor components of
bifurcated bonds; CH
O, OH
the stabilization of crystals, hostguest interactions, and

biomolecules.48
3.7
Halogen bonds
The concept of halogen bonding was largely pioneered

by Resnati and Metrangolo in the 1990s and 2000s.4952
The simplest definition of a halogen bond is an attractive interaction between an electron-deficient halogen atom
(i.e., the donor) and an electron-rich atom (i.e., the acceptor).49, 53 Experimental and theoretical studies demonstrate
that the angle defined by the covalent bond and halogen bond interaction involving the donor atom exhibits
a strong tendency toward linearity.54 The formation of
a halogen bond can be accompanied with the elongation
of the covalent bond that links the halogen atom to the
rest of the donor molecule.50 Halogen atoms attached to
electron-withdrawing substituents, such as perfluorinated
or unsaturated (e.g., acetylenic, aromatic) groups, act as
better halogen bond donors compared to parent hydrocarbon residues (Figure 7).52 Less electronegative atoms and
anions make better halogen-bond acceptors. The N-atom is,
thus, a significantly more efficient halogen-bond acceptor
than the O-atom, and the I-atom provides a better acceptor
than very strong N-bases (e.g., dimethylaminopyridine).55
The covalent bond elongation and linearity of halogen bond interaction are explained by the -hole concept.49, 56 The -hole represents the deformation of the
electron density on the donor halogen atom, resulting in
the formation of an area of diminished electron density that
roughly coincides with the *-antibonding orbital of the
covalent bond between the halogen and remaining donor
molecule. The area of positive potential is responsible for
halogen bond formation through the attractive interaction
with the electron-rich acceptor. Strong halogen bonding
can lead to partial donation of the acceptor electron density into the *-antibonding orbital, hence leading to elongation of the covalent bond. The -hole is encircled by
a ring of negative potential, which actively hinders the
Figure 7 Crystal packing view of ,-diiodoperfluoroalkanes

encapsulated through interactions between the hosts I and the
guests iodine.
approach of acceptor atoms, leading to the pronounced

linear nature of the halogen-bonding interaction. Although
computational and gas-phase studies have suggested that
halogen bonds can adopt a considerable range of strengths
between 10 and 200 kJ mol1 ,50 the forces typically encountered in solids lie between 10 and 50 kJ mol1 .57
While there are very few studies of halogen bond
complexation in solution, there are numerous examples
in the solid state.49, 50, 58, 59 Early cases of halogen bonds
involved simple molecules such as molecular iodine or
iodoform.60 An example is the the cocrystal of molecular
sulfur (S8 ) and iodoform wherein the halogen bond involves
between iodine
an unusually short separation of 3.52 A
61
and sulfur atoms (Figure 8a). A series of isostructural
cocrystals has more recently been described by Cincic and
coworkers wherein I- and Br-atoms resulted in isostructural
solids when used as donors for halogen bond formation
(Figure 8b).55 Auffinger and coworkers have proposed the
importance of halogen bonds in biology.62 A survey of
protein and nucleic acid structures revealed halogen bond
contacts with possible stabilizing roles in protein folding
and ligand binding.63
DOI: 10.1002/9780470661345.smc003
Concepts
I
S
F
Br
(a)
(b)
Figure 8 X-ray crystal structures of (a) the molecular sulfur iodoform cocrystal and (b) isostructural cocrystals sustained by halogen
bonds.55, 61
3.8 interactions
depending on relative charge distribution and the latter on

contact surface area. The edge-to-face geometry of benzene
is more stable on the order of 12 kcal mol1 .67 Both
edge-to-face and face-to-face geometries have successfully
described the complexation of aromatics within structurally
diverse hosts where complementary electrostatic interactions play a role.66, 6971
In the solid state, -surfaces tend to self-organize into
either a stacked or herringbone motif. Desiraju and Gavezzoti have shown that the assembly of fused-ring aromatics
(e.g., naphthalene) depends on the number and positioning of C- and H-atoms within a molecule.72 The predictive
nature is, thus, based on topological and shape considerations of molecules. The relative ability of molecules
to participate in C C and C H forces was also a
Interactions between -surfaces play a role in determining the assembly of biological molecules, with the
sequence-dependent structure of DNA being a prominent
example.64, 65 Theoretical and experimental studies have
provided an understanding of the nature of interactions.6568 Computational studies have revealed that aromatic rings tend to adopt orientations generally based on
edge-to-face and face-to-face geometries.67 At least three
possible structures for the benzene dimer, which is an
important reference, are recognized; namely, offset parallel,
T-shaped edge-to-face, and tilted-T structure (Figure 9).67
The energies of interaction are generally divided into
a columbic and van der Waals term, with the former
Angle
(degrees)
180
Attraction
(a)
90
Attraction
Repulsion
(b)
Repulsion
Offset
()
(c)
(d)
Figure 9 Three geometries of the benzene dimer: (a) face-to-face, (b) offset parallel, (c) T-shaped, edge-to-face, and (d) interaction
between idealized -atoms at various geometries. (Adapted from Ref. 67. American Chemical Society, 2001.)
DOI: 10.1002/9780470661345.smc003
(a)
Figure 10
(b)
Examples of sandwich and crystal packings represented by pyrene and coronene respectively.73, 74
determining factor. The packings were demonstrated to fit

into a herringbone, sandwich-herringbone, (parallel), or
(graphitic planes) motif (Figure 10).73, 74
3.9
Cation and anion interactions
The cation interaction involves binding of a cation to electrons (e.g., benzene, acetylene). Early mass spectrometry and ion cyclotron resonance studies have established
that alkali-metal cations (e.g., Na+ ) bind strongly to simple aromatics.75 Later, Deakyne, and Meotner showed that
organic ions (e.g., alkylammoniums) display affinities for
aromatics.76 Moreover, extensive work by Dougherty and
coworkers has established models of the cation interaction that have been successfully demonstrated in a variety
of synthetic receptors.77
The cation interaction is considered to be electrostatic and to also contain a component of polarization. An
aromatic system such as benzene possesses a permanent
quadrupole moment that defines regions of relative negative
charge above and below the plane. A cation will experience a favorable attractive force with the negative region in
the form of an electrostatic interaction. Synthetic receptors
in the form a cyclophanes have demonstrated the importance of cation interactions in molecular recognition,
while structural effects have been directly observed using
single-crystal X-ray crystallography.25, 7884 Work by Gokel
and coworkers involving lariat crown ethers has revealed
a structural role of the cation interaction to stabilize

conformation, with the interaction of Na+ and indole being
a highlight (Figure 11a).8587 The interaction between a tertiary ammonium ion and toluene has also been structurally
characterized in a sandwich complex (Figure 11b).88
The anion interaction has gained significant recognition in recent years.90, 91 Compared to the cation interaction, the anion interaction is counterintuitive since
anions are expected to exhibit repulsive interaction with
aromatic systems. Theoretical studies in the 1990s and
early 2000s, however, have shown that aromatics deficient
in electron density (e.g., hexafluorobenzene) exhibit favorable interactions with anions, with binding energies on
the order of hydrogen bonds (i.e., 2050 kJ.mol1 ).9296
The interaction involves electrostatic and polarization
components, with the former being correlated with the
quadrupole moment of an electron-deficient ring and the
latter being anion induced. Much experimental evidence
for anion interaction comes from studies of organic
and metal-organic receptors developed for anion binding
(Figure 12).97, 98 A recent analysis of the Cambridge Structural Database by Hay and Custelcean, however, addresses
previous assignments of anion interactions. Examples
of anion interactions with uncharged, and positively
charged, arenes were, moreover, concluded as extraordinary, with only a small number of structures meeting the
geometric requirements of anion interactions predicted
by theory.99
I
Co
Na
(a)
Cl
(b)
Figure 11 (a) X-ray crystal structures of cation interactions between Na+ and indole of a lariat crown ether and (b) five-component
assembly sustained by ammonium and ionion interactions between ammonium and CoCl4 (disordered toluene hydrogen atoms
omitted for clarity).88, 89
DOI: 10.1002/9780470661345.smc003
Concepts
Ni
F
Br
Sb
(a)
(b)
Figure 12 (a) Crystal structure of a 4 : 1 complex of tetracyanopyrazine bromide and (b) crystal structure of a nickel-based
molecular pentagon, which encapsulates SbF6 and participates in
anion interactions (counterions and solvent molecules omitted
for clarity).97, 98
can be a simple inorganic anion, monoatomic cation, or

a biomolecule (e.g., hormones, neurotransmitter).103
Initially, host and guest were classified depending upon
topological relationships between hosts and guests. Hosts
with intramolecular cavities were cavitands that allow binding of guests in solution or solid state to form cavitates. Hosts with extramolecular cavities were clathrands
that incorporated guests only in the solid state to form
clatharates.8, 104, 105 Extensive classifications of hostguest
compounds consider supramolecular interactions between
host and guest8 as being in a complex. Recently, hosts
constructed via the self-assembly of smaller building units
have been developed (e.g., capsules, spheroids).106
6
4
CONSTRUCTION OF
SUPRAMOLECULAR COMPOUNDS
Supramolecular interactions are susceptible to being

deformed and destroyed in the liquid phase and gas phase,
while structural consequences are frozen and accentuated in the solid state. Both the flexibility and repetition of
supramolecular forces are favored by biological and crystallization processes to accomplish self-correction. A main
challenge for supramolecular chemists is to understand
how to employ weak noncovalent interactions to construct
supramolecular compounds. The construction and properties of a supramolecular ensemble will involve molecular
recognition and self-assembly of constituent components.
In line with the enzyme-substrate lock-and-key mechanism,
the interacting partners can comprise host and guest species.
HOSTGUEST CHEMISTRY
The area of hostguest chemistry has experienced remarkable growth, with an 11-volume publication dedicated to the
field.8, 100 Hosts have been synthesized with applications in
areas that range from catalysis to drug delivery and from
pharmaceutical materials to energy storage.101
H. M. Powell proposed a definition of a cagelike,
hostguest structure.102 The term clatharate designated
an inclusion compound wherein two or more components
are associated without ordinary chemical union but through
complete enclosure of one set of molecules in a suitable
structure formed by another. The host is a molecular entity
with convergent binding sites (e.g., Lewis basic donor atom,
hydrogen bond donors), while the guest possesses divergent
sites (e.g., spherical and Lewis acidic metal cation). The
host can be a large molecule akin to an enzyme or a
small molecule with a cavity. The guest, for instance,
MOLECULAR RECOGNITION
Molecular recognition is an integral part of hostguest

chemistry and supramolecular synthesis, being a process
by which molecules select and bind each other in a
structurally well-defined pattern of complementarity and
supramolecular forces.7 For example, a substrate can be
selectively recognized by an enzyme and bound in a
specific orientation in an active site. Similarly, adenine
recognizes thymine in duplex DNA. The functionality of
one molecule complements the other and the two molecules
associate by sharing noncovalent information. From the
perspective of the lock-and-key mechanism,3 the lock is
the molecular receptor and the key is the substrate being
recognized to form a receptorsubstrate complex. The idea
of complementarity has been a central focus of research in
the field of supramolecular chemistry.107
The birth of molecular recognition is traced to the work
of Pedersen on crown ethers and Lehn on cryptands, and
related work on spherands by Cram.14 The size of the metal
cation and diameter of the binding site defined by the etheral
groups in the hosts determined selectivities. High affinities were seen via complementarity of hostguest pairs.
Following work on hostguest chemistry, synthetic receptors with differing concave shapes such as clefts,108 armatures,109 tweezers,110 and bowls111, 112 that bind molecules
were reported. Processes of molecular recognition and binding were then applied to develop self-assembly.
SELF-ASSEMBLY
The idea of self-assembly can be traced to studies of

the tobacco mosaic virus (TMV). TMV is formed by a
protein sheath enclosing single-stranded RNA. The protein
subunits provide the shape of the helix, while RNA
defines the length.113 The components of TMV can be
DOI: 10.1002/9780470661345.smc003
H
N
(a)
Figure 13
H
O
O
H
O
N
Dipyridone subunits
(b)
Cytosine subunit
Guanine subunits
Two classes of self-assembly: (a) homomeric with identical dipyridones and (b) heteromeric with cytosine and guanine.121
disassembled in vitro and reassembled to form the virus.114

All information necessary to build the virus is, thus,
encoded in the individual components. TMV provides
fundamental principles for self-assembly that are as follows:
(i) economy of molecular information of subunits, (ii)
control of association through multiple interactions, (iii)
self-correction to avoid synthetic errors, and (iv) overall
efficiency by assembly of subunits. Additional principles of
self-assembly such as self-organization were realized from
studies of Anifinsen on protein folding.115
Although numerous definitions for self-assembly exist,
the definition of Whitesides is apt for a discussion related
to supramolecular forces.106, 116118 Whitesides defines selfassembly as the spontaneous assembly of molecules into
structured, stable, noncovalently joined aggregates.117 The
structural integrity of the self-assembled aggregate is maintained after formation because it represents the thermodynamically most stable structure. Four important properties of self-assembly are as follows: (i) properties of selfassembled aggregates are unique from the subunits from
which they are composed, (ii) reversibility of the selfassembly allows an improperly formed assembly or mismatch of subunits to be eliminated from the final structure
through self-correcting, (iii) individual subunits contain all
information necessary for a self-assembled structure, and
(iv) subunits bind cooperatively via supramolecular interactions to form the most stable structure. Indeed, selfassembly is inextricably associated with molecular recognition since the recognition of the individual components
of the aggregate by each other directs the construction of
the supramolecular compound.106, 116, 117
Chemists have recognized a variety of self-assembly processes in supramolecular chemistry. The self-assembly of
hostguest or receptorsubstrate and crystals are examples
that provide the basis for the field of molecular recognition and solid-state chemistry. Different types of selfassemblies have been topics of extensive reviews.106, 116, 117
For example, Lawrence has classified self-assembling
complexes as cyclic arrays, infinite arrays, cylindrical

arrays, dendrimeric arrays, helical arrays, receptors, catenanes, and rotaxanes.119 Self-assembly can also be divided
into homomeric and heteromeric. Homomeric (i.e., selfcomplementary) includes self-assembled structures formed
by utilizing the same subunits. Heteromeric includes selfassembled structures constructed by different subunits
(Figure 13).119121
SUPRAMOLECULAR STRUCTURES
VIA MOLECULAR RECOGNITION
AND SELF-ASSEMBLY
In a covalent synthesis, bond formation is generally irreversible and attributed to enthalpy and kinetic stability of
products (Table 3). Terms such as bond energy, stereoelectronic effects, and strain are applied in a traditional
sense. In a supramolecular synthesis, the product is an
equilibrating structure that involves comparable balances
between enthalpy and entropy. Thus, a supramolecular
product is considered for a thermodynamic minimum evaluation. Moreover, a noncovalent synthesis provides a challenge to manipulate multiple equilibria in supramolecular
design and synthesis.122 Numerous strategies to design and
construct supramolecular compounds have been achieved
using molecular recognition and self-assembly involving
aggregates and networks, which typically form in solution
and in the solid state, respectively. Examples that highlight the utility of employing supramolecular interactions
to construct self-assembled structures are given below to
demonstrate features of design strategies.
8.1
Aggregates in solution
Early work of Whitesides employed hydrogen bonds

between cyanuric acid and melamine to construct supramolecular aggregates in solution (Figure 13).122124 Three
DOI: 10.1002/9780470661345.smc003
10
Concepts
Table 3
Comparison of covalent and noncovalent syntheses.
Properties
Covalent
Noncovalent
Constituent bond types

Bond strengths (kcal mol1 )
Stability of bonds in the product
Contributions to G
Strategy of design
Importance of solvent effects
Covalent
25200
Kinetically stable
Usually dominated by H
Selective reaction
Secondary
Ionic, hydrophobic, hydrogen bonds

0.120
Kinetically reversible
H and T S are often comparable
Directed equilibrium
Primary
melamine units linked to a central hub afforded molecule

B that was compatible with the conformation of cyanuric acid/melamine hexagonal lattice.106 Mixing of B
with three equivalents of the alkyl cyanuric acid A produced a 1 : 3 complex in an aprotic solvent (e.g., chloroform) (Figure 14a). The aggregate, effectively, contained
one layer of the cyanuric acid/melamine lattice capped
by the trisubstituted hub. A related decamolecular aggregate was reported. The stability of the aggregates can
be ascribed the preorganization of the melamine subunits
and conformational compatibility of the melamine trimer
with cyanuric acid/melamine lattice.123 In related work,
Zimmerman has utilized hydrogen bonds to stabilize a
self-assembled dendrimer based on a cyclic hexamerization.125 Dendritic wedges with isopthalic groups underwent
self-association to afford dendrimers of 30 kDa molecular
weight (Figure 14b). Linear aggregation was also favored
by changing functional groups along the periphery of
wedges.126
The ability of hydrogen bonds to produce self-assembled
capsules was demonstrated in an early work by Rebek and
later by MacGillivray and Atwood (Figure 15).127, 128 In
the former, diphenylglycouril units self-assembled via eight
hydrogen bonds to produce an internal cavity that resembled
(a)
(b)
Figure 15 Capsules by self-assembly of (a) glycouril subunits

and (b) resorcin[4]arenes.127, 128
a molecular tennis ball (Figure 15a).127 In the latter, a bowlshaped resorcin[4]arene was self-assembled, along with
eight water molecules, to form a hexameric spheroidal
sustained by 60 hydrogen bonds (Figure 15b).128 The
topology of the sphere conformed to an Archimedean snub
cube. Extensive studies by Fujita,129 Stang,130 Raymond,131
Mirkin,132 and others have employed coordination bonds to
construct similar polygonal and polyhedral hosts via selfassembly.
R
NH2
N
O
R
O
N
H
HN
N
N
3.
O
H
O
H
N
NH
+
O
N
O
O
H
O
O
H
O
O
H O
O H
O
O
N
H
H O
O
H
O
H O
O H
A
R
Br
O
H
O
Figure 14
(b)
H O
O
H
O
O
H
O
O
O H
(a)
H O
O H
H
O
H O
O
O H
Aggregates in solution: (a) 1 : 3 complex of hub B with melamines and cyanuric acid A and (b) dendritic hexamer.
DOI: 10.1002/9780470661345.smc003
O
H
O
8.2
Networks in the solid state
Work of Etter on the recognition of patterns of hydrogen

bonds in the solid state defined using graph set notation is
also important in this regard.135137
A main tenant of crystal engineering is to recognize
and design synthons to control the assembly of molecules
and ions in solids. Supramolecular synthons have been
utilized for the controlled synthesis of one-dimensional
(1D), two-dimensional (2D), and three-dimensional (3D)
networks, many of which exhibit tailorable properties
(Figure 16).47, 133
Wuest demonstrated the ability of organic building units
to self-assemble in the solid state via hydrogen bonds to
form 3D frameworks with topologies akin to diamond.
Self-assembled pyridone dimers, referred to as tectons,
that possess a rigid tetra-arylcore with the pyridones
held rigidly at a fixed distance were exploited to control
molecular aggregation in three dimensions.138140 Tectons
The use of supramolecular interactions to control the

structure of organic solids has been well documented by
Desiraju.16, 47, 133 Corey introduced the term synthon for
the retrosynthetic analysis of complex target molecules.134
Desiraju introduced supramolecular synthon for the construction of supramolecular targets in the solid state.133
According to Desiraju, supramolecular synthons are structural units within supermolecules that can be formed and/or
assembled by known or conceivable synthetic operations
involving intermolecular interactions. Supramolecular synthons define spatial arrangements of intermolecular interactions required for a supramolecular synthesis and, thus, play
a conceptually similar role of synthons in molecular syntheses. In doing so, Desiraju outlined crystal engineering
as a domain in the designed construction of organic solids.
R
O
(a)
11
Carboxylic acid dimer synthon
H
O
O
O
O
O
H
O
O
H
O
H
H
O
O
H
R
H
O
O
H O
O
H
(b)
(c)
Figure 16 Benzoic acid dimer (a), trimesic acid trigonal network (b), and adamantane-1,3,5,7 tetracarboxylic acid diamondoid network
(c) via the carboxylic acid dimer.47, 133
DOI: 10.1002/9780470661345.smc003
12
Concepts
O
HN
H
N
NH
Tecton
H
N
Figure 17
Diamondoid network from hydrogen-bonded tectons based on pyridones.140
(a)
Figure 18
(b)
2D frameworks sustained by (a) carboxylic acid dimers and (b) halogen bonds between iodines atoms.141, 142
on crystallization with barbituric acid led to the hydrogenbond-directed formation of interpenetrating diamondoid
networks with butyric acid molecules occupying voids
(Figure 17).140
Two-dimensional networks sustained by hydrogen bonds
and halogen bonds in the form of cocrystals have been
reported (Figure 18).141, 142 In the former, Zaworotko and
coworkers showed that cocrystallization of the linear
bifunctional hydrogen-bond acceptor 4,4 -bipyridine with
the trigonal trifunctional hydrogen-bond donor trimesic
acid (TMA) affords a 2D hexagonal chickenwire framework sustained by hydrogen bonds (Figure 18a).141 The
hexagons, which adopted a chair conformation, were of
and exhibited selfdimensions approximately 35 26 A
inclusion. The network was, effectively, an enlarged analog
of the hexagonal network of pure TMA with hexagons
In the latter, Metrangolo and coworkers
of 14 14 A.
reported that cocrystallization of ammonium, sulfonium,
and phosphonium iodides with 1,3,5-triiodotrifluorbenzene

produces a honeycomb framework supported by halogen
bonds with cations as guests (Figure 18b).142 A match
between cation size and halogen-bond donor was exploited
to separate ,-diiodoperfluoroalkanes of different lengths
via the reversible formation of the ionic lattices.
Coordination polymers and metal-organic frameworks
(MOFs) are representative examples that demonstrate
how coordination bonds can be used to construct selfassembled networks. In a seminal work, Robson described
scaffolding-like coordination polymers based on the selfassembly of tetrahedral and octahedral metal cyanides
with linear organic rods. The materials comprise very
large adamantane-like cavities that readily underwent ion
exchange (Figure 19a).32 The solids were complements
to microporous solids such as zeolites. Structurally similar MOFs involving linear carboxylate bridges and metal
clusters as nodes have been developed by Yaghi and
DOI: 10.1002/9780470661345.smc003
Cu
Zn
13
6. J. M. Lehn, Pure Appl. Chem., 1978, 50, 871.

7. J. M. Lehn, Angew. Chem., Int. Ed., 1988, 27, 89.
8. J. W. Steed and J. L. Atwood, Supramolecular Chemistry,
2nd ed., John Wiley & Sons, Ltd, Chichester, 2009.
9. M. Faraday and J. Davy, Philos. Trans. R. Soc. London,
1823, 113, 160.
10. Y. A. Ovchinnikov, V. T. Ivanov, and A. M. Scrob, Membrane Active Complexones, Elsevier, New York, 1974.
(a)
(b)
11. M. M. Blight and N. F. Curtis, J. Chem. Soc., 1962, 1204.
Figure 19 X-ray crystal structures of (a) adamantane-like structure based on CuI[4,4 ,4 ,4 -tetracyanotetraphenylmethane]BF4
and (b) MOF-5 (solvent and counterions omitted for clarity).32, 146
12. J. D. Curry and D. H. Busch, J. Am. Chem. Soc., 1964, 86,

592.
13. E. Jager, Z. Chem., 1968, 8, 392.
14. C. J. Pedersen, J. Am. Chem. Soc., 1967, 89, 2495.
others.143145 A form of isoreticular synthesis has been

described that enables the extended structures of MOFs to
be retained and can be easily modified to achieve control
of pore structure and connectivity (Figure 19b).146 A wide
range of functional groups can been incorporated into the
inner pores of MOFs.147152 The frameworks have experienced applications in areas such as catalysis and gas
storage.153156
15. D. J. Cram, Angew. Chem., Int. Ed., 1988, 27, 1009.

16. G. R. Desiraju, Nature, 2001, 412, 397.
17. J. M. Lehn, Science, 1993, 260, 1762.
18. G. R. Desiraju, Crystal Engineering: The Design of Organic
Solids, Elsevier, New York, 1989.
19. A. J. Goshe, I. M. Steele, C. Ceccarelli, et al., Proc. Natl.
Acad. Sci. U. S. A., 2002, 99, 4823.
20. J. J. Novoa, E. DOria, and M. A. Carvajal, Understanding
the Nature of the Intermolecular Interactions in Molecular
Crystals. A Theoretical Perspective, Wiley-VCH Verlag
GmbH & Co. KGaA, 2007.
CONCLUSIONS
Understanding how molecules and ions interact provides

insight into the design and construction of supramolecular
compounds. Interactions between molecules constitute the
basis of hostguest chemistry, molecular recognition, and
self-assembly. Whereas the parameters that define many
supramolecular interactions are reasonably well established,
structural manifestations of noncovalent forces and understanding the nuances of weak interactions continues to
provide a major challenge for chemists. Controlling the
ability of supramolecular interactions to dictate molecular organization, particularly in unusual environments (e.g.,
constrained media, cells), is expected to be of significant
importance as supramolecular chemistry develops into a
science of complex matter157 with implications in materials
science, biology, and health.
21. P. J. Garratt, Y. F. Ng, and J. W. Steed, Tetrahedron, 2000,

56, 4501.
22. J. W. Steed, Chem. Commun., 2006, 2637.
23. C. A. Ilioudis, D. A. Tocher, and J. W. Steed, J. Am. Chem.
Soc., 2004, 126, 12395.
24. V. A. Parsegian, van der Waals Forces: A Handbook for
Biologists, Chemists, Engineers, and Physicists, Cambridge
University Press, New York, 2006.
25. D. A. Stauffer, and D. A. Dougherty, Tetrahedron Lett.,
1988, 29, 6039.
26. A. J. Blake, R. O. Gould, S. Parsons, et al., Acta Crystallogr., Sect. C: Cryst. Struct. Commun., 1996, 52, 24.
27. P. Pyykko, Chem. Rev., 1997, 97, 597.
28. Q. L. Chu, D. C. Swenson, and L. R. MacGillivray,
Angew. Chem., Int. Ed., 2005, 44, 3569.
29. U. E. I. Horvath, J. M. McKenzie, and S. Cronje, et al.,
Chem. Commun., 2009, 6598.
30. A. Werner, Ann. Chem., 1912, 386, 1.
REFERENCES
31. A. Werner, Ber. Dtsch. Chem. Ges., 1912, 45, 121.

32. B. F. Hoskins and R. Robson, J. Am. Chem. Soc., 1990,
112, 1546.
1. F. Wohler, Ann. Phys. Chem., 1828, 12, 253.

2. K. C. Nicolaou, D. Vourloumis, N. Winssinger,
P. S. Baran, Angew. Chem., Int. Ed., 2000, 39, 44.
and
3. E. Fischer, Ber. Dtsch. Chem. Ges., 1894, 27, 2985.

4. J. M. Lehn, Supramolecular Chemistry: Concepts and Perspectives, VCH, Weinheim, 1995.
5. G. R. Desiraju, Nature, 2000, 408, 407.
33. B. J. Holliday and C. A. Mirkin, Angew. Chem., Int. Ed.,

2001, 40, 2022.
34. R. W. Saalfrank, H. Maid, and A. Scheurer, Angew. Chem.,
Int. Ed., 2008, 47, 8794.
35. S. Sato, Y. Ishido, and M. Fujita, J. Am. Chem. Soc., 2009,
131, 6064.
DOI: 10.1002/9780470661345.smc003
14
Concepts
36. N. L. Rosi, J. Eckert, M. Eddaoudi, et al., Science, 2003,

300, 1127.
65. C. D. M. Churchill, L. R. Rutledge, and S. D. Wetmore,

Phys. Chem. Chem. Phys., 2010, 12, 14515.
37. X. Zhao, B. Xiao, A. J. Fletcher, et al., Science, 2004, 306,

1012.
66. C. A. Hunter, J. K. M. Sanders, J. Am. Chem. Soc., 1990,

112, 5525.
38. R. Kitaura, S. Kitagawa, Y. Kubota, et al., Science, 2002,

298, 2358.
67. W. B. Jennings, B. M. Farrell, and J. F. Malone, Acc.

Chem. Res., 2001, 34, 885.
39. D. Maspoch, D. Ruiz-Molina, K. Wurst, et al., Nat. Mater.,

2003, 2, 190.
68. C. D. Sherrill, Computations of Noncovalent Interactions,

John Wiley & Sons, Inc., 2009.
40. E. Coronado, J. R. Galan-Mascaros, C. J. Gomez-Garcia,

and V. Laukhin, Nature, 2000, 408, 447.
69. C. A. Hunter, Chem. Soc. Rev., 1994, 23, 101.
41. A. R. Millward and O. M. Yaghi, J. Am. Chem. Soc., 2005,

127, 17998.
71. M. C. T. Fyfe and J. F. Stoddart, Acc. Chem. Res., 1997,

30, 393.
42. S. Leininger, B. Olenyuk, and P. J. Stang, Chem. Rev.,

2000, 100, 853.
72. G. R. Desiraju and A. Gavezzotti, Acta Crystallogr., Sect.

C: Cryst. Struct. Commun., 1989, 45, 473.
43. G. A. Jeffrey, An Introduction to Hydrogen Bonding,

Oxford University Press, New York, 1997.
73. R. Allman, Z. Kristallogr., 1970, 132, 129.
44. L. Pauling, J. Am. Chem. Soc., 1931, 53, 1367.
74. J. K. Fawcett and J. Trotter, Proc. R. Soc. London, Ser. A,

1965, 289, 366.
45. L. Pauling, The Nature of the Chemical Bond and the

Structure of Molecules and Crystals; an Introduction to
Modern Structural Chemistry, Cornell University Press, H.
Milford; Oxford University Press, Ithaca, NY, 1939.
46. G. R. Desiraju, Angew. Chem., Int. Ed., 2011, 50, 52.
47. G. R. Desiraju, Acc. Chem. Res., 2002, 35, 565.
48. T. Steiner and G. Koellner, J. Mol. Biol., 2001, 305, 535.
49. P. Metrangolo, H. Neukirch, T. Pilati, and G. Resnati, Acc.
Chem. Res., 2005, 38, 386.
50. P. Metrangolo, F. Meyer, T. Pilati, et al., Angew. Chem.,
Int. Ed., 2008, 47, 6114.
51. P. Metrangolo and G. Resnati, Science, 2008, 321, 918.
52. P. Metrangolo, Y. Carcenac, M. Lahtinen, et al., Science,
2009, 323, 1461.
53. J. M. Dumas, M. Gomel, and M. Guerin, in The Chemistry
of Functional Groups, Supplement D, eds. S. Patai and
Z. Rappoport, John Wiley & Sons Ltd, New York, 1983,
985.
70. S. K. Burley and G. A. Petsko, Science, 1985, 229, 23.
75. J. Sunner, K. Nishizawa, and P. Kebarle, J. Phys. Chem.,

1981, 85, 1814.
76. C. A. Deakyne and M. Meotner, J. Am. Chem. Soc., 1985,
107, 474.
77. J. C. Ma and D. A. Dougherty, Chem. Rev., 1997, 97, 1303.
78. T. J. Shepodd, M. A. Petti, and D. A. Dougherty, J. Am.
Chem. Soc., 1986, 108, 6085.
79. T. J. Shepodd, M. A. Petti, and D. A. Dougherty, J. Am.
Chem. Soc., 1988, 110, 1983.
80. M. A. Petti,
T. J. Shepodd,
R. E. Barrans,
and
D. A. Dougherty, J. Am. Chem. Soc., 1988, 110, 6825.
81. P. C. Kearney, L. S. Mizoue, R. A. Kumpf, et al., J. Am.
Chem. Soc., 1993, 115, 9907.
82. J. E. Forman, R. E. Barrans, and D. A. Dougherty, J. Am.
Chem. Soc., 1995, 117, 9213.
83. D. A. Stauffer, R. E. Barrans, and D. A. Dougherty, J. Org.
Chem., 1990, 55, 2762.
54. A. Legon, in Halogen Bonding, vol. 126, eds P. Metrangolo

and G. Resnati, Springer, Berlin/Heidelberg, 2008, p. 17.
84. D. A. Dougherty and D. A. Stauffer, Science, 1990, 250,

1558.
55. D. Cincic, T. Frisc ic, and W. Jones, Chem. Eur. J., 2008,
14, 747.
85. G. W. Gokel, L. J. Barbour, R. Ferdani, and J. X. Hu, Acc.

Chem. Res., 2002, 35, 878.
56. A. C. Legon, Phys. Chem. Chem. Phys., 2010, 12, 7736.
86. S. L. De Wall, E. S. Meadows, L. J. Barbour, and

G. W. Gokel, Proc. Natl. Acad. Sci. U. S. A., 2000, 97,
6271.
57. R. B. Walsh, C. W. Padgett, P. Metrangolo, et al., Cryst.

Growth Des., 2001, 1, 165.
58. H. A. Bent, Chem. Rev., 1968, 68, 587.
87. J. X. Hu, L. J. Barbour, and G. W. Gokel, Proc. Natl.

Acad. Sci. U. S. A., 2002, 99, 5121.
59. S. Triguero, R. Llusar, V. Polo, and M. Fourmigue, Cryst.

Growth Des., 2008, 8, 2241.
88. L. R. MacGillivray and J. L. Atwood, Angew. Chem., Int.

Ed., 1996, 35, 1828.
60. F. Guthrie, J. Chem. Soc., 1863, 239.

61. T. Bjorvatten, Acta Chem. Scand., 1962, 16, 749.
89. S. L. De Wall, E. S. Meadows, L. J. Barbour,

G. W. Gokel, J. Am. Chem. Soc., 1999, 121, 5613.
62. P. Auffinger, F. A. Hays, E. Westhof, and P. S. Ho, Proc.

Natl. Acad. Sci. U. S. A., 2004, 101, 16789.
90. P. D. Beer and P. A. Gale, Angew. Chem., Int. Ed., 2001,

40, 486.
63. E. Parisini, P. Metrangolo, T. Pilati, et al., Chem. Soc. Rev.,

2011, 40, 2267.
91. B. L. Schottel, H. T. Chifotides, and K. R. Dunbar, Chem.

Soc. Rev., 2008, 37, 68.
64. W. Saenger, Principles of Nucleic Acid Structure, SpringerVerlag, New York, 1984.
92. D. Quinonero, C. Garau, C. Rotger, et al., Angew. Chem.,

Int. Ed., 2002, 41, 3389.
DOI: 10.1002/9780470661345.smc003
and
15
93. I. Alkorta, I. Rozas, and J. Elguero, J. Org. Chem., 1997,

62, 4687.
121. H. Tanaka, D. Shiomi, T. Ise, et al., Cryst. Eng. Comm.,

2007, 9, 767.
94. J. P. Gallivan and D. A. Dougherty, Org. Lett., 1999, 1,

103.
122. G. M. Whitesides, E. E. Simanek, J. P. Mathias, et al.,

Acc. Chem. Res., 1995, 28, 37.
95. Y. Danten, T. Tassaing, and M. Besnard, J. Phys. Chem. A,

1999, 103, 3530.
123. J. P. Mathias,
E. E. Simanek,
C. T. Seto,
and
G. M. Whitesides, Angew. Chem., Int. Ed., 1993, 32,
1766.
96. M. Mascal, A. Armstrong, and M. D. Bartberger, J. Am.

Chem. Soc., 2002, 124, 6274.
97. Y. S. Rosokha, S. V. Lindeman, S. V. Rosokha, and
J. K. Kochi, Angew. Chem., Int. Ed., 2004, 43, 4650.
98. C. S. Campos-Fernandez, B. L. Schottel, H. T. Chifotides,
et al., J. Am. Chem. Soc., 2005, 127, 12909.
99. B. P. Hay and R. Custelcean, Cryst. Growth Des., 2009, 9,
2539.
100. J. L. Atwood, J. E. D. Davies, and F. Vogtle, Comprehensive Supramolecular Chemistry, vol. 111, Pergamon
Oxford, 1996.
124. J. P. Mathias, E. E. Simanek, J. A. Zerkowski, et al., J.

Am. Chem. Soc., 1994, 116, 4316.
125. S. V. Kolotuchin and S. C. Zimmerman, J. Am. Chem. Soc.,
1998, 120, 9092.
126. S. C. Zimmerman, F. W. Zeng, D. E. C. Reichert, and
S. V. Kolotuchin, Science, 1996, 271, 1095.
127. R. Wyler, J. de Mendoza, and J. Rebek, Angew. Chem., Int.
Ed., 1993, 32, 1699.
128. L. R. MacGillivray and J. L. Atwood, Nature, 1997, 389,
469.
101. S.-i. Noro, S. Kitagawa, M. Kondo, and K. Seki, Angew.

Chem., Int. Ed., 2000, 39, 2081.
129. M. Fujita, M. Tominaga, A. Hori, and B. Therrien, Acc.

Chem. Res., 2005, 38, 369.
102. H. M. Powell, J. Chem. Soc., 1948, 61.
130. S. R. Seidel and P. J. Stang, Acc. Chem. Res., 2002, 35,

972.
103. D. J. Cram, Container Molecules and Their Guests, Cambridge, 1994.

104. F. Vogtle, H.-G. Lohr, J. Franke, and D. Worsch, Angew.
Chem., Int. Ed., 1985, 24, 727.
105. F. Vogtle, Supramolecular Chemistry, Wiley, Chichester,
1991.
131. D. L. Caulder and K. N. Raymond, Acc. Chem. Res., 1999,

32, 975.
132. N. C. Gianneschi, M. S. Masar, and C. A. Mirkin, Acc.
Chem. Res., 2005, 38, 825.
133. G. R. Desiraju, Angew. Chem., Int. Ed., 1995, 34, 2311.
106. D. Philp and J. F. Stoddart, Angew. Chem., Int. Ed., 1996,

35, 1154.
134. E. J. Corey, Pure Appl. Chem., 1967, 14, 19.
107. J. Rebek, Top. Curr. Chem., 1988, 149, 189.
136. M. C. Etter, J. Phys. Chem., 1991, 95, 4601.
108. J. Rebek, Science, 1987, 235, 1478.
137. M. C. Etter and S. M. Reutzel, J. Am. Chem. Soc., 1991,

113, 2586.
109. J. C. Adrian and C. S. Wilcox, J. Am. Chem. Soc., 1989,

111, 8055.
110. S. C. Zimmerman and W. M. Wu, J. Am. Chem. Soc., 1989,
111, 8054.
111. P. E. J. Sanderson, J. D. Kilburn, and W. C. Still, J. Am.
Chem. Soc., 1989, 111, 8314.
112. S. Paliwal, S. Geib, and C. S. Wilcox, J. Am. Chem. Soc.,
1994, 116, 4497.
135. M. C. Etter, Acc. Chem. Res., 1990, 23, 120.
138. M. Gallant, M. T. P. Viet, and J. D. Wuest, J. Am. Chem.

Soc., 1991, 113, 721.
139. M. Simard, D. Su, and J. D. Wuest, J. Am. Chem. Soc.,
1991, 113, 4696.
140. X. Wang, M. Simard, and J. D. Wuest, J. Am. Chem. Soc.,
1994, 116, 12119.
113. K. Namba and G. Stubbs, Science, 1986, 231, 1401.
141. C. V. K. Sharma and M. J. Zaworotko, Chem. Commun.,

1996, 2655.
114. H. Fraenkel-Conrat and R. C. Williams, Proc. Natl. Acad.

Sci. U. S. A., 1955, 41, 690.
142. P. Metrangolo, F. Meyer, T. Pilati, et al., Chem. Commun.,

2008, 1635.
115. C. B. Anfinsen, Science, 1973, 181, 223.

116. J. S. Lindsey, New J. Chem., 1991, 15, 153.
143. S. S. Y. Chui, S. M. F. Lo, J. P. H. Charmant, et al., Science, 1999, 283, 1148.
117. G. M. Whitesides, J. P. Mathias, and C. T. Seto, Science,

1991, 254, 1312.
144. G. Ferey, C. Serre, C. Mellot-Draznieks, et al., Angew.

Chem., Int. Ed., 2004, 43, 6296.
118. J. R. Fredricks and A. D. Hamilton, in Comprehensive

Supramolecular Chemistry, vol. 9, eds J. L. Atwood,
J. E. D. Davies, D. MacNicol, and F. Vogtle, Pergamon,
New York, 1996, 565.
145. M. Eddaoudi, J. Kim, N. Rosi, et al., Science, 2002, 295,

469.
119. D. S. Lawrence, T. Jiang, and M. Levett, Chem. Rev., 1995,

95, 2229.
147. S. Shimomura, M. Higuchi, R. Matsuda, et al., Nat. Chem.,

2010, 2, 633.
120. Y. Ducharme and J. D. Wuest, J. Org. Chem., 1988, 53,

5787.
148. R. Matsuda, R. Kitaura, S. Kitagawa, et al., Nature, 2005,

436, 238.
146. H. Li, M. Eddaoudi, M. OKeeffe, and O. M. Yaghi,

Nature, 1999, 402, 276.
DOI: 10.1002/9780470661345.smc003
16
Concepts
149. K. L. Mulfort and J. T. Hupp, J. Am. Chem. Soc., 2007,

129, 9604.
154. O. M. Yaghi, M. OKeeffe, N. W. Ockwig, et al., Nature,

2003, 423, 705.
150. J.-P. Zhang and S. Kitagawa, J. Am. Chem. Soc., 2008, 130,
907.
155. G. Ferey, Chem. Soc. Rev., 2008, 37, 191.
151. K. K. Tanabe, Z. Wang, and S. M. Cohen, J. Am. Chem.

Soc., 2008, 130, 8508.
Miljanic, et al., Science, 2009, 325,
152. Q. Li, W. Zhang, O. S.
855.
156. A. C. McKinlay, R. E. Morris, P. Horcajada, et al., Angew.

Chem., Int. Ed., 2010, 49, 6260.
157. J. M. Lehn, Proc. Natl. Acad. Sci. U. S. A., 2002, 99,
4763.
153. S. Kitagawa, R. Kitaura, and S.-I. Noro, Angew. Chem., Int.

Ed., 2004, 43, 2334.
DOI: 10.1002/9780470661345.smc003

SMC 003

Încărcat de

Informații document

Descriere originală:

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

SMC 003

Încărcat de

Drepturi de autor:

Formate disponibile

Supramolecular Interactions

Dushyant B. Varshey, John R. G. Sander, Tomislav Frisc ic,

To achieve the impeccable ability of nature to construct

construction of complex molecules, otherwise unavailable

Development of supramolecular chemistry

The concepts and roots of supramolecular chemistry can

Figure 1 An illustration of molecular versus supramolecular

Supramolecular compounds are formed by additive and

Humphrey Davy in 1810.8, 9 Development was initiated

Bond energies (kJ mol1 )

as the interplay, of such interactions is a major goal of

Directional versus nondirectional

Ionion and van der Waals

Ionion and van der Waals forces lie at extremes in

Figure 4 X-ray crystal structure of K+ encapsulated by

Iondipole and dipoledipole interactions result from

Closed-shell metalmetal interactions

Interactions between closed-shell metal cations of d8 -d10 -s2

Iondipole and dipoledipole interactions

While the structural manifestations of coordination bonds

Figure 5 Agentophilic and aurophilic interactions in crystalline: (a) dinuclear

intermediate strength and, similar to hydrogen bonds,

The hydrogen bond, owing to a relatively strong and highly

Figure 6 Hydrogen bonding: (a) carboxylic acid dimer and

nature, dictating the recognition of substrates by enzymes

Properties of hydrogen bonds.8, 16, 43

the stabilization of crystals, hostguest interactions, and

The concept of halogen bonding was largely pioneered

Figure 7 Crystal packing view of ,-diiodoperfluoroalkanes

approach of acceptor atoms, leading to the pronounced

depending on relative charge distribution and the latter on

determining factor. The packings were demonstrated to fit

Cation and anion interactions

a structural role of the cation interaction to stabilize

can be a simple inorganic anion, monoatomic cation, or

Supramolecular interactions are susceptible to being

Molecular recognition is an integral part of hostguest

The idea of self-assembly can be traced to studies of

disassembled in vitro and reassembled to form the virus.114

complexes as cyclic arrays, infinite arrays, cylindrical

Early work of Whitesides employed hydrogen bonds

Comparison of covalent and noncovalent syntheses.

Constituent bond types

Ionic, hydrophobic, hydrogen bonds

melamine units linked to a central hub afforded molecule

Figure 15 Capsules by self-assembly of (a) glycouril subunits

Networks in the solid state

Work of Etter on the recognition of patterns of hydrogen

The use of supramolecular interactions to control the

Carboxylic acid dimer synthon

Diamondoid network from hydrogen-bonded tectons based on pyridones.140

and phosphonium iodides with 1,3,5-triiodotrifluorbenzene

6. J. M. Lehn, Pure Appl. Chem., 1978, 50, 871.

11. M. M. Blight and N. F. Curtis, J. Chem. Soc., 1962, 1204.

12. J. D. Curry and D. H. Busch, J. Am. Chem. Soc., 1964, 86,

others.143145 A form of isoreticular synthesis has been

15. D. J. Cram, Angew. Chem., Int. Ed., 1988, 27, 1009.

Understanding how molecules and ions interact provides

21. P. J. Garratt, Y. F. Ng, and J. W. Steed, Tetrahedron, 2000,

31. A. Werner, Ber. Dtsch. Chem. Ges., 1912, 45, 121.

1. F. Wohler, Ann. Phys. Chem., 1828, 12, 253.

3. E. Fischer, Ber. Dtsch. Chem. Ges., 1894, 27, 2985.