Issue 12, 2013

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

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.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
21 May 2013
Accepted
19 Aug 2013
First published
20 Aug 2013
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2013,4, 4417-4425

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

D. Bučar, G. M. Day, I. Halasz, G. G. Z. Zhang, J. R. G. Sander, D. G. Reid, L. R. MacGillivray, M. J. Duer and W. Jones, Chem. Sci., 2013, 4, 4417 DOI: 10.1039/C3SC51419F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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