198 Topics in Current Chemistry Editorial Board: A. de Meijere KN ...

60 A. Nangia · G.R. Desiraju
electrostatic and include hydrogen bonds and heteroatom interactions (see also
the article by J.P. Glusker in this volume). The observed three-dimensional architecture
in the crystal is the result then of the interplay between the demands of
isotropic van der Waals forces whose magnitude is proportional to the size of the
molecule, and anisotropic hydrogen bond interactions whose strengths are related
to donor atom acidities and acceptor group basicities.The crystal structures of
hydrocarbon molecules are largely dictated by close packing arguments while the
structures of molecules containing heteroatoms and functional groups are dominated
by hydrogen bonds and anisotropic interactions [2, 6].
3
Supramolecular Synthons and Networks
The synthesis of complex natural products and aesthetically-pleasing molecules
has been practised by organic chemists for decades. It was in 1967 that Corey
introduced a formalism in organic synthesis to organise the sequence of steps,
and consequently to focus the chemical thought process, from starting material
to the target substance [7]. Corey defined synthons as “structural units within
molecules which can be formed and/or assembled by known or conceivable
synthetic operations”and the term has been used since its inception to represent
key structural units in target molecules. A synthon is usually smaller and less
complex than the target molecule and yet contains most of the vital bond
connectivity and stereochemical information required to synthesise the goal
substance. The dissection of a complex target molecule into simpler synthons is
performed through a series of logical and rational bond disconnections and this
exercise is termed retrosynthetic analysis [8].
By analogy with synthons, supramolecular synthons are structural units
within supermolecules which can be formed and/or assembled by known or
conceivable intermolecular interactions, and crystal engineering is the solid
state supramolecular equivalent of organic synthesis [9]. Just as in traditional
organic synthesis, where the retrosynthetic bond disconnections must be
carried out in accordance with the reactivity of functional groups and their
stereochemical preferences [10], so is the case in supramolecular retrosynthesis
wherein the complex interplay of close packing, hydrogen bonding and other
intermolecular interactions during crystallisation must be analysed and exploited
[11]. Supramolecular synthons are spatial arrangements of intermolecular
interactions and play the same focussing role in supramolecular synthesis
that conventional synthons do in molecular synthesis. Scheme 1 shows a few
important supramolecular synthons 1–13.
The advantage of using the synthon approach is that it offers a considerable
simplification in the understanding of crystal structures. For example, the same
carboxy dimer motif 1 is present in the structures of benzoic acid, terephthalic
acid, isophthalic acid, trimesic acid and adamantane-1,3,5,7-tetracarboxylic
acid in zero-, one-, two- and three-dimensional arrangements [9] (see also the
article by R.E. Meléndez and A.D. Hamilton in this volume).
The emphasis in crystal engineering may be increasingly diverted from the
constituent molecules to the topological features and geometrical connectivities