Predicting spontaneous racemate resolution using recent developments in crystal structure prediction
Predicting spontaneous racemate resolution using recent developments in crystal structure prediction
复制标题
利用晶体结构预测的最新进展预测自发外消旋体拆分
作者：
J. Kendrick;Matthew D. Gourlay;M. Neumann;F. Leusen
采用分子力学和量子力学混合固态DFT方法对四种分子的外消旋和对映体纯晶体结构的稳定性进行了重新排序； 4-羟甲基-2-恶唑烷酮、5-羟甲基-2-恶唑烷酮、2-(4-羟基苯基)-2,5,5-三甲基吡咯烷-1-氧基和2-(3-羟基苯基)-2,5,5-三甲基吡咯烷-1-氧基。先前使用基于力场的方法来预测这些晶体结构的工作表明，晶格能量可能是预测手性分子是否会在结晶时自发分解的合适标准。然而，在某些情况下，该方法预测了与实验观察到的结构相对应的不切实际的高晶格能量。混合 DFT 方法成功预测了那些自发分解的分子，并进一步预测了所有实验观察到的结构的令人满意的晶格能量。根据对两种方法预测的晶格能量的比较，得出的结论是，所使用的力场不足以准确地预测自发分辨率。然而，混合 DFT 方法被证明对于进行此类预测足够准确。
A hybrid molecular mechanics and quantum mechanics solid state DFT method is used to re-rank the stability of racemic and enantiopure crystal structures of four molecules; 4-hydroxymethyl-2-oxazolidinone, 5-hydroxymethyl-2-oxazolidinone, 2-(4-hydroxyphenyl)-2,5,5-trimethylpyrrolidine-1-oxy and 2-(3-hydroxyphenyl)-2,5,5-trimethylpyrrolidine-1-oxy. Previous work using a force field based method to predict these crystal structures indicated that the lattice energy may be a suitable criterion for predicting whether a chiral molecule will resolve spontaneously on crystallisation. However, in some cases, the method had predicted an unrealistically high lattice energy for the structure corresponding to the experimentally observed one. The Hybrid DFT method successfully predicts those molecules which resolve spontaneously and furthermore predicts satisfactory lattice energies for all experimentally observed structures. Based on a comparison of the predicted lattice energies from the two methods it is concluded that the force fields used were not sufficiently accurate to predict spontaneous resolution with any confidence. However, the Hybrid DFT method is shown to be sufficiently accurate for making such predictions.