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

Crystalline Polymorphism of Organic Compounds 173
(~ 3.2 Å) of the respective layers shown in Fig. 4. This example conveys an idea
of the variations in polymorphic structural arrangements that are possible with
molecules containing hydrogen bonding functionalities.
During the last few years, the development of graph set analysis [16] has
greatly facilitated the visualisation and comparison of polymorphic structures.
Here, hydrogen bonding networks are classified as belonging to one of four
distinct patterns, each specified by a designator (G in general): intramolecular
(S), chains (C), rings (R), or other finite patterns (D). Further specification of the
number of donor (d) and acceptor (a) atoms as well as the total number of atoms
(n) comprising the pattern yields a concise and informative description of the
hydrogen bonding arrangement, G a d(n).A simple illustration of the use of graph
set descriptors is given in Fig. 5 for a polymorph of thalidomide (space group
C2/c, Z=8) [62]. Alternating hydrogen bonded ring motifs exist in this polymorphic
structure as a result of bifurcated hydrogen bonding involving the
N-H group. In contrast, the other known racemic modification of thalidomide
(space group P2 1/n, Z=4) [63] contains only centrosymmetric dimers of the
type R 2 2(8). Application of graph set analysis to three polymorphs of iminodiacetic
acid [64] has led not only to facile comparison of the crystal structures, but
has also provided a basis for concise description of the polymorphic transformations
occurring in that system. Thus, e.g. transformation of one polymorph
of the acid into another is simply described as a conversion of R 2 2(4) into R 2 4(8).
It has been pointed out that graph set analysis of hydrogen bonded systems also
provides a means for seeking systematic correlations between the resultant
patterns that demonstrate “hydrogen bond pattern functionality”[16].This concept
may be useful in the prediction of crystal structures as well as for the design
of materials with desired supramolecular features. Extension of the graph
set approach to encompass intermolecular atom-atom interactions other than
hydrogen bonding for the classification of polymorphic crystal structures is
envisaged as a natural and desirable development and more widespread use of
this classification can be expected in future.
Elucidation of detailed polymorphic structural features and structural changes
accompanying polymorphic transformations relies heavily on the single
crystal X-ray diffraction technique. The inability to produce single crystals in
Fig. 5. Graph set notation for hydrogen bonded ring motifs in a polymorph of thalidomide