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

Crystalline Polymorphism of Organic Compounds 203
a b
Fig. 15 a Schematic illustration of the packing arrangement in a polar and a centrosymmetric
crystal. b The effect of a designed inhibitor on crystal growth. (Adapted from [36] with
permission
clustering associated with the formation of pre-critical nuclei of crystalline
phases. The relevance for organic crystal polymorphism is that direct observation
of the dynamics of crystal nucleation could elucidate the effects of additives
on polymorphic control. Much of this work has been based on the use of Langmuir
films to induce nucleation at the air-water interface [36]. To illustrate the
level of interpretation which is currently possible from such experiments, a
recent study of the self-assembly of crystalline monolayers and multilayers of
n-alkanes on a water surface is cited [167]. Surface observations were carried out
using synchrotron grazing incidence X-ray diffraction and specular X-ray
reflectivity. These allowed detailed characterisation of the crystalline films
including determination of their space groups. It is noteworthy that these were
found to be identical to those of the corresponding three-dimensional crystals,
thus demonstrating that the full crystal symmetry already exists even for
crystallites whose thickness corresponds to only a few molecular layers.
Related to the above strategy is the concept of engineering solid surfaces for
promoting nucleation and epitaxial growth of desired polymorphs. If it is assumed
that the pre-nucleation aggregate for a polymorph resembles the mature
crystal, it should be possible to design a surface which mimics a particular
crystal plane of the desired species, and upon which heterogeneous nucleation
will occur and epitaxial polymorphic growth will result. This has been realised
in the technique of ledge-directed epitaxy [168] in which the intersection of a
terrace plane and a step on a crystal surface (a “ledge”) functions as a nucleation
site for organic crystals. For polymorphic control, the crucial requirement is that
two well-defined, close-packed crystal planes of the polymorph have a dihedral