Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
J Am Chem Soc. 2020 Jun 17;142(24):10755-10768. doi: 10.1021/jacs.0c02097. Epub 2020 Jun 3.
Predicting the crystallization of chiral molecules from solution is a major challenge in the chemical sciences. In this paper, we use molecular dynamics computer simulations to study the crystallization of a family of coarse-grained models of chiral molecules with a broad range of molecular shapes and interactions. Our simulations reproduce the experimental crystallization behavior of real chiral molecules, including racemic and enantiopure crystals, as well as amorphous solids. Using efficient algorithms for the packing of shapes, we enumerate millions of low-energy crystal structures for each model and analyze the thermodynamic landscape of polymorphs. In agreement with recent conjectures, our analysis shows that the ease of crystallization is largely determined by the number of competing polymorphs with low free energy. We find that this number and, hence, crystallization outcomes depend on molecular interactions in a simple way: Strongly heterogeneous interactions across molecules promote crystallization and favor the spontaneous resolution of racemic mixtures. Our results help rationalize a number of experimental observations and can provide guidance for the design of molecules and experimental conditions for desired crystallization outcomes.
从溶液中预测手性分子的结晶是化学科学的一个主要挑战。在本文中，我们使用分子动力学计算机模拟来研究一系列具有广泛分子形状和相互作用的粗粒模型的手性分子的结晶。我们的模拟再现了真实手性分子的实验结晶行为，包括外消旋和对映纯晶体以及非晶固体。使用用于形状堆积的有效算法，我们为每个模型枚举了数百万个低能量晶体结构，并分析了多晶型物的热力学景观。与最近的推测一致，我们的分析表明，结晶的容易程度在很大程度上取决于具有低自由能的竞争多晶型物的数量。我们发现，这个数量，因此，结晶结果以简单的方式取决于分子相互作用：分子之间强烈的不均匀相互作用促进了结晶，并有利于外消旋混合物的自发拆分。我们的结果有助于合理化许多实验观察结果，并为设计所需结晶结果的分子和实验条件提供指导。
