Screening for cocrystals of succinic acid and 4-aminobenzoic acid

Nizar Issa, Sarah A. Barnett, Sharmarke Mohamed, Doris E. Braun, Royston C.B. Copley, Derek A. Tocher, Sarah L. Price

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

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·2,2′-bipyridine (1:1, P2 1/c, I), succinic acid·diphenylcyclopropenone (1:2, P2 1/c, II), 4-aminobenzoic acid·antipyrine (1:1, P2 1, III) and 4-aminobenzoic acid·phenazine (1:2, P1, IV), are reported. The computed crystal energy landscapes of the cocrystals and their components show why succinic acid·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·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.

Original languageBritish English
Pages (from-to)2454-2464
Number of pages11
JournalCrystEngComm
Volume14
Issue number7
DOIs
StatePublished - 7 Apr 2012

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