Solvation and surface effects on polymorph stabilities at the nanoscale.
Solvation and surface effects on polymorph stabilities at the nanoscale.
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DOI：
10.1039/c6sc03457h
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发表时间：
2016-11-01
期刊：
影响因子：
8.4
通讯作者：
Sanders JKM
中科院分区：
文献类型：
--
作者：
Belenguer AM;Lampronti GI;Cruz-Cabeza AJ;Hunter CA;Sanders JKM
我们探讨了粒度和溶剂环境对两对多晶型物进行球磨纯磨（NG）和液体辅助研磨（LAG）的热力学稳定性的影响。我们探讨了粒度和溶剂环境对两对多晶型物进行球磨纯磨（NG）和液体辅助研磨（LAG）的热力学稳定性的影响。研究了两种体系：（i）1：1茶碱：苯甲酰胺共晶体的I型和II型，以及（ii）芳香族二硫化物化合物的A型和B型。对于这两个系统，最稳定的本体多晶型转化为亚稳态本体多晶型后NG。LAG实验根据所用溶剂的量产生不同的结果。通过使用增加μL量的不同性质的溶剂进行仔细控制的LAG实验，进一步研究了这一点。通过这些实验，我们能够监测作为溶剂浓度的函数的A型至B型和I型至II型的转化率，并得到多晶型物平衡曲线。发现在多晶型产物中切换所需的浓度取决于溶剂性质。我们建议，这些实验表明在研磨罐中的多晶型物的热力学稳定性的开关。形式B，稳定的本体多晶型物，具有比形式A更不稳定的表面，因此当表面效应变得重要时，在纳米级变得亚稳定。非原位衍射和电子显微镜数据证实，在球磨机研磨实验达到平衡后，晶体尺寸在几十纳米的量级。多晶型物颗粒稳定性的DFT-d计算支持这些发现，并用于计算作为溶剂函数的A型和B型的交叉尺寸。附着能和暴露的各种晶面的表面稳定性被发现是非常敏感的溶剂环境。我们的研究结果表明，表面效应是显着的，在纳米级的多态性和平衡球磨机NG和LAG实验的结果一般由热力学控制。
We explore the effects of particle size and solvent environment on the thermodynamic stability of two pairs of polymorphs subjected to ball-mill neat grinding (NG) and liquid assisted grinding (LAG). We explore the effects of particle size and solvent environment on the thermodynamic stability of two pairs of polymorphs subjected to ball-mill neat grinding (NG) and liquid assisted grinding (LAG). Two systems were studied: (i) forms I and II of a 1 : 1 theophylline : benzamide cocrystal and (ii) forms A and B of an aromatic disulfide compound. For both systems, the most stable-bulk polymorph converted to the metastable-bulk polymorph upon NG. LAG experiments yielded different outcomes depending on the amount of solvent used. This was further investigated by performing carefully controlled LAG experiments with increasing μL amounts of solvents of different nature. With these experiments, we were able to monitor form A to B and form I to II conversions as a function of solvent concentration and derive polymorph equilibrium curves. The concentration required for a switch in polymorphic outcome was found to be dependent on solvent nature. We propose that these experiments demonstrate a switch in thermodynamic stability of the polymorphs in the milling jar. Form B, the stable-bulk polymorph, has less stable surfaces than form A, thus becoming metastable at the nanoscale when surface effects become important. Ex situ diffraction and electron microscopy data confirm crystal sizes in the order of tens of nanometers after the ball mill grinding experiments reach equilibrium. DFT-d computations of the polymorph particles stabilities support these findings and were used to calculate cross-over sizes of forms A and B as a function of solvent. Attachment energies and surface stabilities of the various crystalline faces exposed were found to be very sensitive to the solvent environment. Our findings suggest that surface effects are significant in polymorphism at the nanoscale and that the outcomes of equilibrium ball-mill NG and LAG experiments are in general controlled by thermodynamics.