Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
J Am Chem Soc. 2021 Dec 29;143(51):21580-21593. doi: 10.1021/jacs.1c09321. Epub 2021 Dec 17.
Kinetics can play an important role in the crystallization of molecules and can give rise to polymorphism, the tendency of molecules to form more than one crystal structure. Current computational methods of crystal structure prediction, however, focus almost exclusively on identifying the thermodynamically stable polymorph. Kinetic factors of nucleation and growth are often neglected because the underlying microscopic processes can be complex and accurate rate calculations are numerically cumbersome. In this work, we use molecular dynamics computer simulations to study simple molecular models that reproduce the crystallization behavior of real chiral molecules, including the formation of enantiopure and racemic crystals, as well as polymorphism. A significant fraction of these molecules forms crystals that do not have the lowest free energy. We demonstrate that at high supersaturation crystal formation can be accurately predicted by considering the similarities between oligomeric species in solution and molecular motifs in the crystal structure. For the case of racemic mixtures, we even find that knowledge of crystal free energies is not necessary and kinetic considerations are sufficient to determine if the system will undergo spontaneous chiral separation. Our results suggest conceptually simple ways of improving current crystal structure prediction methods.
动力学在分子结晶中起着重要的作用，并可能导致多晶型现象，即分子形成多种晶体结构的倾向。然而，目前的晶体结构预测计算方法几乎完全专注于识别热力学稳定的多晶型物。成核和生长的动力学因素通常被忽略，因为潜在的微观过程可能很复杂，并且准确的速率计算在数值上很繁琐。在这项工作中，我们使用分子动力学计算机模拟来研究简单的分子模型，这些模型再现了真实手性分子的结晶行为，包括对映纯和外消旋晶体以及多晶型现象的形成。这些分子的很大一部分形成的晶体没有最低自由能。我们证明，在高过饱和度下，可以通过考虑溶液中低聚物物种与晶体结构中分子基元之间的相似性来准确预测晶体的形成。对于外消旋混合物的情况，我们甚至发现不需要知道晶体自由能，而只需考虑动力学因素就足以确定系统是否会发生自发的手性分离。我们的结果表明了改进当前晶体结构预测方法的概念上简单的方法。
