The curious case of (caffeine)•(benzoic acid): how heteronuclear seeding allowed the formation of an elusive cocrystal
The curious case of (caffeine)•(benzoic acid): how heteronuclear seeding allowed the formation of an elusive cocrystal
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DOI：
10.1039/c3sc51419f
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发表时间：
2013-01-01
期刊：
影响因子：
8.4
通讯作者：
Jones, William
中科院分区：
文献类型：
--
作者：
Bucar, Dejan-Kresimir;Day, Graeme M.;Jones, William
晶体是一种模块化的多组分固体，在合成化学和材料科学中具有特殊的用途。制备共晶体的方法多种多样，然而，一些很有前途的共晶相已被证明是难以合成的目标。我们描述了一种合成药物相关的(咖啡因)(苯甲酸)共晶体(1)的策略，它一直无法使用广泛的已有技术形成。使用最先进的晶体结构预测方法来评估热力学稳定形式1的可能存在，从而确定适合共结晶的异核种子。一旦被引入，设计的异核种子促进了1的形成，值得注意的是，它们(或产品共晶的种子)继续充当长期的实验室“污染物”，这鼓励了共晶的形成，即使存在的水平很低，以至于无法被检测到。所描述的晶种技术使合成在所需条件下不能获得的共晶成为可能，并潜在地标志着材料研究领域的一个新方向。
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.