The supramolecular synthon approach to crystal structure prediction

Abstract

A new approach has been proposed for the ab initio crystal structure prediction of small organic molecules. This exercise forms a part of the recent blind test on crystal structure prediction conducted by the Cambridge Crystallographic Data Centre. The method uses as a starting point lists of low energy structures generated by an exhaustive computational procedure, namely, the Polymorph Predictor program in Cerius². Such computational procedures take into account only the enthalpic factors in crystallization. A further difficulty is that information relating to crystallization kinetics is very hard to obtain directly. However, such kinetic information is implicitly contained in the experimental structures that are found in crystallographic databases. Therefore, in our approach, the low energy structures obtained in the Polymorph Predictor program are reranked after consideration of experimental structures of structurally similar molecules. Operationally, this is most conveniently carried out after identification of possible supramolecular synthons in the Cambridge Structural Database. These synthons are representative structural units that convey critical information that relates isolated molecules with their resulting crystal structures. Of the three molecules in the blind test, the present approach was fully successful for one, but only of limited utility in the two others. Reasons for this variability of success are given.