The ability of the pharmaceutically acceptable cocrystallising agents, succinic acid and 4-aminobenzoic acid, to form cocrystals with ten small organic molecules with hydrogen bonding acceptors but no donors, was investigated by grinding, hot-stage microscopy and solution based crystallisation experiments.

The reproducible results obtained by different methods showed that only six cocrystals formed. The crystal structures of the four novel cocrystals, succinic acid(cas:110-15-6) 2,2′-bipyridine (1:1, P21/c, I), succinic acid(cas:110-15-6) diphenylcyclopropenone (1:2, P21/c, II), 4-aminobenzoic acid?antipyrine (1:1, P21, III) and 4-aminobenzoic acid?phenazine (1:2, P, IV), are reported. The computed crystal energy landscapes of the cocrystals and their components show why succinic acid(cas:110-15-6) 1,4-dicyanobenzene did not form a cocrystal as well as predicting the observed structure of succinic acid?2,2′-bipyridine as the most stable. The most stable hypothetical structures of a 1:1 succinic acid(cas:110-15-6) 1,4-dicyanobenzene cocrystal are closely related to those of the components.

The results demonstrate that cocrystal formation requires both hydrogen bonding and close packing, and so markedly non-planar pharmaceuticals will be quite specific in the steric and hydrogen bonding disposition requirement of coformers.