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

174 M.R. Caira
the laboratory (especially for metastable polymorphs) has hindered progress in
research on polymorphism. If, however, a polymorph is available in a powdered
crystalline form and a computational method exists for predicting possible
three-dimensional crystal structures, then the latter can be used to generate
computed X-ray powder patterns for comparison with the experimental pattern.
While the scope of the present review does not permit detailed exposition of the
approaches and algorithms employed in crystal structure prediction, a summary
of some recent developments, especially as they relate to polymorphism, is
in order. The studies of polymorphism and crystal structure prediction are
indeed two facets of the same topic [65]. Additional powerful motivations for
predicting crystal structures include a better understanding of the crystallization
process as well as the design of new solid materials. The reader is referred
to several recent treatments of crystal structure prediction [66–70]. Comments
on some of these methods and their applications follow.
In the atom-atom potential (AAP) method as implemented in the program
PROMET [66], symmetry operations (e.g. a screw axis, centre of inversion)
appropriate to the chosen space group, are applied to a molecule in fixed conformation
(possibly optimised previously by a molecular mechanics calculation)
to generate molecular clusters. Following a search for the most stable
clusters on the potential hypersurface (calculated using empirical atom-atom
potentials), translation is applied to generate one or more periodic structures.
Packing energies are computed and acceptable structures are optimised. This is
a very useful means of generating a series of polymorphic structures for a given
molecule. In this approach, consideration is usually given to only the most
populous space groups (93% of organic molecules being confined to 18 space
groups [71]) thereby running a small risk of an incorrect choice. If an experimental
X-ray powder pattern of the material is available, the correct crystal
structure may be identified by comparison with computed powder patterns
from the candidate structures generated by PROMET. In a study using this procedure
[72] several literature cases were selected, for each of which the crystal
structure of one polymorph had been determined, and mention was made of the
existence of a second polymorph whose crystals were unsuitable for complete
structural elucidation by X-ray analysis. Only unit cell and space group data
were available for these undetermined polymorphs. Each starting molecular
conformation was assumed to be the same as that in the corresponding fully
characterised polymorph and was submitted to the PROMET procedure. In all
cases, satisfactory structures were generated, with predicted unit cell data in
good agreement with the experimental ones and with packing energies in the
expected ranges. These results represent authentic crystal structure prediction,
assisted by partial X-ray data. The method is therefore an alternative to direct
methods of structural solution and also implies that, provided cell and space
group information can be acquired, full structure determination without diffraction
data is feasible. The authors of this study are less optimistic as regards
true ab initio crystal structure prediction for numerous reasons, among them
that packing energies for polymorphs of the same compound are always very
similar, rendering the choice of the correctly computed structure difficult in the
absence of other data, and that the occurrence of polymorphs containing mole-