The curious case of (caffeine)·(benzoic acid): how heteronuclear seeding allowed the formation of an elusive cocrystal

• DOI: 10.1039/c3sc51419f
• Publication Date: 2013-08-20T12:35:39Z
• Authors: Dejan-Krešimir Bučar; Graeme M. Day; Ivan Halasz; Geoff G. Z. Zhang; John R. G. Sander; David G. Reid; Leonard R. MacGil...; Melinda J. Duer; William Jones
• Keywords: Cocrystal; Heteronuclear molecule; Synthon; Benzoic acid

Cocrystals are modular multicomponent solids with exceptional utility in synthetic chemistry and materials science. A variety of methods exist for the preparation cocrystals, yet, some promising cocrystal phases have proven to be intractable targets. We describe a strategy synthesis pharmaceutically relevant (caffeine)·(benzoic acid) (1), which persistently failed form using broad range established techniques. State-of-the-art crystal structure prediction were employed assess possible existence thermodynamically stable 1, hence identify appropriate heteronuclear seeds cocrystallization. Once introduced, designed facilitated formation 1 and, significantly they (or product cocrystal) continued act as long-lasting laboratory "contaminants", encouraged even when present at such low levels evade detection. The seeding technique described thus enables cocrystals regarded unobtainable under desired conditions, potentially signifies new direction field research.