Pushing Technique Boundaries to Probe Conformational Polymorphism.
Pushing Technique Boundaries to Probe Conformational Polymorphism.
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DOI：
10.1021/acs.cgd.3c00641
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发表时间：
2023-10-04
影响因子：
3.8
通讯作者：
Oswald, Iain D H
中科院分区：
文献类型：
--
作者：
Ward, Martin R;Taylor, Christopher R;Mulvee, Matthew T;Lampronti, Giulio I;Belenguer, Ana M;Steed, Jonathan W;Day, Graeme M;Oswald, Iain D H
我们提出了一个广泛的探索的固体形态景观的氯磺丙脲（CPA）使用相结合的实验计算方法在这两个领域的前沿。我们已经获得了新的构象多晶型的CPA，将它们与已知的形式，使用灵活的分子晶体结构预测的背景下。我们强调了通过喷雾干燥实验形成的一种新的多晶型物（α-CPA），尽管其相对于热力学α-形式具有显着的亚稳性（14 kJ/mol），并且我们鉴定并解析了2019年分离的球磨η-形式。此外，我们采用杂质和凝胶辅助结晶来控制多晶型和新的多组分形式的形成。因此，我们展示了这种协作筛选方法的力量，以观察，合理化和控制新的亚稳态形式的形成。我们提出了一个广泛的探索的固体形态景观氯磺丙脲使用相结合的实验-计算方法在这两个领域的前沿。
We present an extensive exploration of the solid-form landscape of chlorpropamide (CPA) using a combined experimental–computational approach at the frontiers of both fields. We have obtained new conformational polymorphs of CPA, placing them into context with known forms using flexible-molecule crystal structure prediction. We highlight the formation of a new polymorph (ζ-CPA) via spray-drying experiments despite its notable metastability (14 kJ/mol) relative to the thermodynamic α-form, and we identify and resolve the ball-milled η-form isolated in 2019. Additionally, we employ impurity- and gel-assisted crystallization to control polymorphism and the formation of novel multicomponent forms. We, thus, demonstrate the power of this collaborative screening approach to observe, rationalize, and control the formation of new metastable forms. We present an extensive exploration of the solid-form landscape of chlorpropamide using a combined experimental−computational approach at the frontiers of both fields.