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

Supramolecular Synthons and Pattern Recognition 83
portion of the antibiotic indicates that the receptor cavity has a well-defined
geometry and that shape recognition occurs without much ligand-induced fit.
8
Polymorphism
Polymorphism is defined as the phenomenon wherein the same chemical substance
exists in different crystalline forms [68]. In the context of the present
article, polymorphism corresponds to the existence of different crystalline
patterns for the same molecule. With the current levels of intense activity in
crystal engineering, there is much interest in this well-known though littleunderstood
phenomenon [69]. There is as yet no clear consensus on the exact
definition of polymorphism. McCrone defined it as the existence of at least two
crystalline arrangements in the solid state of the same chemical substance [70]
while Buerger and Bloom defined it on the basis that the two polymorphs must
have distinctive properties [71]. Some of the criteria employed for assessing the
existence of polymorphs are differences in unit cell parameters, crystal packing
arrangements and physical properties. Among the techniques used for identifying
polymorphs, single crystal and powder X-ray diffraction are the most
powerful, while others like hot-stage microscopy, IR spectroscopy and differential
scanning calorimetry provide supporting evidence.
Dunitz has expressed a more contemporary view of polymorphism [3]. Since
a crystal is a supermolecule, polymorphic forms are superisomers and polymorphism
is a kind of superisomerism. Similar ideas are implicit in the molecule
Æ supermolecule analogy and crystalline polymorphs are the supramolecular
equivalents of molecular structural isomers [9]. Polymorphism in crystals
is a very complex issue, and this complexity relates not only to causes for its
occurrence but also to criteria that can judge as to whether it is present at all.
Conformational polymorphism [72] and configurational polymorphism are
two different types of polymorphism that arise because molecules adopt different
conformations or crystallise as geometrical isomers, diastereomers, enantiomers
or tautomers in the solid state. The suggestion of Byrn that polymorphism
is very common in pharmaceutical compounds [73] is illustrated in the
recent high-profile legal battle concerning the polymorphs of one of the best
selling drugs, ranitidine [74]. Pseudopolymorphism, the inclusion of different
solvents in the crystal structures of the same chemical substance, is not, strictly
speaking, polymorphism at all because it involves different chemical species.
This notwithstanding, the phenomenon is of immediate concern to the pharmaceutical
industry while filing patent applications because different solvates of the
same drug can exhibit widely differing solubilities and bioavailability properties.
The unpredictable and capricious nature of polymorphism has been discussed in
a recent article, humorously entitled “Disappearing Polymorphs” [75].
The existence of polymorphism in crystals can, at one stroke, demolish a wellplanned
and logically devised strategy to obtain a target supramolecular structure.
Instead of treating this phenomenon as a complication or nuisance in
crystal engineering strategies, a more positive approach is to view it as an excellent
opportunity to study the same chemical substance in different crystalline