Polymorphism and structural prediction in molecular crystals
What is it about?
Polymorphism - the adoption of a particular compound of more than one crystal structure - is often found in molecular crystals, but not as frequently as one might expect. This work explores the reasons for this, using several complementary approaches. The novelty of representing molecules as two linked rods provides useful graphical insight into patterns of molecular packing and also takes molecular conformation into account. The conclusions are backed up by using semi-empirical non-bonded potentials optimised for hydrogen bonding. The prospect of structural prediction by rod-rotation about fixed points is also discussed.
Why is it important?
Polymorphism is usually seen as a problem by the pharmaceutical industry, since it is generally difficult to control this. Moreover, the pharmaceutical activity of a particular drug compound is often highly dependent on the crystal structure adopted. By identifying the mechanisms of stabilisation of the alternative crystal structures, this paper provides some useful pointers on how to limit the range of polymorphs found for a particular compound. The methodology can also point to substitutional options that will promote a particular, desirable crystal structure.