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

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

Dejan-Krešimir Bučar, Graeme M Day, Ivan Halasz, Geoff G. Z Zhang, John R. G Sander, David G Reid, Leonard R MacGillivray, Melinda J Duer and William Jones
Chemical science (Cambridge), Vol.4(12), pp.4417-4425
2013
DOI: 10.1039/c3sc51419f
url
https://doi.org/10.1039/c3sc51419fView
Published (Version of record) Open Access

Abstract

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

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