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

Supramolecular Synthons and Pattern Recognition 65
really sampling all the recognition patterns. The absence of rampant polymorphism
in molecular crystals suggests that crystallisation is an inherently
very efficient process that cascades into stable crystal structures.
Crystals are supermolecules and their structural features are best described
in terms of motifs or patterns of interactions, that is supramolecular synthons.
A functional group is a molecular descriptor and does not contain any information
about its hydrogen bond forming ability that is critical to the design and
construction of supermolecules. For example, three of the most common families
of hydrogen bonded compounds – carboxylic acids, primary amides and
alcohols – each have more than one hydrogen bond recognition motif [29]. The
difference between the dimer and catemer motifs 1 and 2 is obvious in acids but
in amides, the chain motifs related by translation and screw or glide appear to
be similar, and yet lead to distinct packing arrangements. Thus, there is a one to
many correspondence between functional groups and synthons. The smallest
structural unit that contains crystallisation information is the supramolecular
synthon, not the functional group.
It should be emphasised that the identification of the set of interactions that
constitutes a synthon is a subjective matter and is at the discretion of the
chemist. Within the limit that every possible combination of interactions is
defined as a supramolecular synthon, the term will fall into disuse much like its
molecular sibling [8, 15]. Interactions or groups of interactions that are needlessly
identified as synthons but are unable subsequently to demonstrate and
sustain a predictive role in crystal structure design will drop out from practical
usage. A convenient working definition of a useful supramolecular synthon is
thus a unit consisting of hydrogen bonds and/or non-polar intermolecular
interactions that has maximum structural information while maintaining an
economy in size.
The terms “maximum” and “economy” are significant. As synthon size is
increased up to the entire unit cell, so does its information content. Conversely,
as synthon size decreases down to just a single interaction, its information content
decreases. However, there is a critical intermediate region wherein all the
crucial structural information is present within units of manageable size. It is
this region that is of the greatest importance to the structural chemist. Implied
in all this of course is synthon robustness, that is the ability of a synthon to reappear
in related structures, in effect controlling self assembly within a crystal
family. This then is another feature that distinguishes synthons from mere interactions.
In summary, rather than attempt an unambiguous and rigorous definition of
the term supramolecular synthon, we feel it best that the scope and meaning of
the term be allowed to refine during the evolution of crystal engineering into a
mature subject.
4.1
Connection Between Molecular and Crystal Structure
In the context of crystal engineering strategies a frequently asked question [30]
is “given the molecular structure of an organic substance, what is its crystal