Dehydration of crystalline solids is a widespread phenomenon, yet the fundamental mechanisms by which dehydration occurs are not properly understood. This arises due to technical limitations in studying such fast processes with sufficient sensitivity; nevertheless, understanding dehydration pathways is critical for designing optimal properties for materials, particularly in the case of pharmaceutical solids. The computational methods presented here allow for accurate determination of the dehydrated species’ crystal structure and to develop an understanding of the mechanism of dehydration at the molecular level. This work also highlights the critical role of explicitly taking into account the dynamical aspect of molecules using computational techniques, rather than relying on static energy minimization approaches. Specifically, the crystalline active pharmaceutical agent naproxen sodium, and its hydrates, is studied in silico using density functional theory and molecular dynamics, ultimately elucidating the face-specific dehydration mechanisms and revealing highly complex diffusion and nucleation behavior. Additionally, the results indicate that the method is a viable way to explore dehydration pathways and predict new dehydrated crystal structures.

中文翻译：

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用分子动力学模拟追踪结晶水合物中的脱水机理

结晶固体的脱水是一种普遍现象，但是对脱水发生的基本机理还没有适当的了解。这是由于在以足够的灵敏度研究这种快速过程中的技术局限性而产生的；但是，了解脱水途径对于设计材料的最佳性能至关重要，特别是在药物固体的情况下。此处介绍的计算方法可以准确确定脱水物质的晶体结构，并有助于在分子水平上理解脱水的机理。这项工作还强调了使用计算技术而不是依靠静态能量最小化方法明确考虑分子动力学方面的关键作用。具体来说，利用密度泛函理论和分子动力学对硅进行了研究，最终阐明了特定于脸部的脱水机制，并揭示了高度复杂的扩散和成核行为。此外，结果表明该方法是探索脱水途径和预测新的脱水晶体结构的可行方法。