Selective desolvation in two-step nucleation mechanism steers crystal structure formation
Selective desolvation in two-step nucleation mechanism steers crystal structure formation
复制标题
两步成核机制中的选择性去溶剂化引导晶体结构形成
DOI：
10.1039/d1nr06346d
复制
发表时间：
2022
期刊：
影响因子：
6.7
通讯作者：
Singh, Meenesh R.
中科院分区：
文献类型：
--
作者：
Dighe, Anish V.;Coliaie, Paria;Podupu, Prem K.;Singh, Meenesh R.
两步成核理论（TSN）和晶体结构预测（CSP）分别是预测成核速率和晶体结构的两种相互脱节但又十分流行的方法。TSN理论是一种成熟的机制，用于描述各种结晶材料在不同溶剂中的成核。然而，它从未被扩展到预测晶体结构或多晶型。相反，现有的CSP技术仅凭经验考虑溶剂效应。因此，TSN理论和CSP技术继续作为单独的方法来预测成核速率和结构的两个基本属性。在这里，我们弥合了这一差距，并首次展示了晶体结构是如何在TSN理论的框架内形成的。TSN中提出了一种顺序去溶剂化机制，其中第一步涉及部分去溶剂化以形成致密的簇，然后是指导晶体结构形成的官能团的选择性去溶剂化。我们研究了使用分子模拟的特定相互作用对谷氨酸分子的不同官能团周围的溶剂化程度的影响。模拟的能量景观和活化障碍，在增加过饱和度表明顺序和选择性去溶剂化。我们通过计算和实验验证了晶体结构的形成和多晶型物的选择是由于以前未被认识到的过饱和驱动的不对称去溶剂化的分子的后果。
The two-step nucleation (TSN) theory and crystal structure prediction (CSP) techniques are two disjointed yet popular methods to predict nucleation rate and crystal structure, respectively. The TSN theory is a well-established mechanism to describe the nucleation of a wide range of crystalline materials in different solvents. However, it has never been expanded to predict the crystal structure or polymorphism. On the contrary, the existing CSP techniques only empirically account for the solvent effects. As a result, the TSN theory and CSP techniques continue to evolve as separate methods to predict two essential attributes of nucleation – rate and structure. Here we bridge this gap and show for the first time how a crystal structure is formed within the framework of TSN theory. A sequential desolvation mechanism is proposed in TSN, where the first step involves partial desolvation to form dense clusters followed by selective desolvation of functional groups directing the formation of crystal structure. We investigate the effect of the specific interaction on the degree of solvation around different functional groups of glutamic acid molecules using molecular simulations. The simulated energy landscape and activation barriers at increasing supersaturations suggest sequential and selective desolvation. We validate computationally and experimentally that the crystal structure formation and polymorph selection are due to a previously unrecognized consequence of supersaturation-driven asymmetric desolvation of molecules.