Efficient Polymorph Screening through Crystallization from Bulk and Confined Melts
Efficient Polymorph Screening through Crystallization from Bulk and Confined Melts
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DOI：
10.1021/acs.cgd.2c01065
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发表时间：
2022-11-22
影响因子：
3.8
通讯作者：
Shtukenberg, Alexander G.
中科院分区：
文献类型：
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作者：
Fellah, Noalle;Tahsin, Lamia;Shtukenberg, Alexander G.
从熔体中结晶可以实现高结晶驱动力，同时伴随着相对缓慢的生长、成核和转化速率，这些特征有利于其用作有效的多晶型物筛选方法。令人惊讶的是，尽管熔融结晶具有悠久的历史，但与溶液结晶相比，它在寻找新多晶型物方面的应用较少。将熔融结晶应用于 21 种高度多晶型的、具有至少五种环境多晶型物的良好表征的化合物表明，熔融结晶提供了一半以上的已知多晶型物，并且在许多情况下揭示了其他筛选方法未检测到的新多晶型物。统计分析表明，从熔体中生长的多晶型物更倾向于高 Z' 值，而其他结晶方案不易获得高 Z' 值，并且通常无法通过晶体结构预测方法检测到。 21 种化合物中的 19 种在纳米孔（8-100 nm）内进行熔融结晶，大部分产生多晶型物，这些多晶型物在相似温度下从本体熔体中结晶为主。然而，在纳米孔中观察到的多晶型物总数少于从本体熔体结晶过程中观察到的多晶型物总数，并且限制下的熔体结晶揭示了其他结晶方法未检测到的新多晶型物。
Crystallization from the melt can allow the achievement of high driving force for crystallization accompanied by relatively slow growth, nucleation, and transformation rates, features that favor its use as an efficient polymorph screening method. Surprisingly, even though melt crystallization has a long history, it has been employed less often in the search for new polymorphs than solution crystallization. Applications of melt crystallization to 21 highly polymorphic, well-characterized compounds with at least five ambient polymorphs revealed that melt crystallization afforded more than half of the known polymorphs and in many cases revealed new polymorphs not detected by other screening methods. A statistical analysis revealed that polymorphs grown from the melt have a greater propensity for high Z ' values, which are not easily accessible by other crystallization protocols and are often not detectable by crystal structure prediction methods. Melt crystallization within nanopores (8-100 nm) performed for 19 of the 21 compounds mostly resulted in polymorphs that dominated crystallization from the bulk melt at similar temperatures. The total number of polymorphs observed in nanopores was less than that observed during crystallization from the bulk melt, however, and melt crystallization under confinement revealed new polymorphs not detected by other crystallization methods.