采用QSPR模型预测手性二芳基甲烷衍生物保留因子与分离因子

摘要

Quantitative structure-property relationship (QSPR) studies on retention and separation factors of chiral compounds play a key role in predicting the retention and separation factors even the elution order of enantiomers. Chiral diarylmethane derivates were selected for computing molecular structural descriptors using VolSurf program. Models were built between the descriptors and retention as well as separation factors. The robustness of the model with respect to separation factors was assessed by external validation through the test set, leave-many-out cross-validation and Y-randomization test. The results were satisfactory. Analysis on the variables shows that the molecular globularity, hydrophilic regions at median energy levels, hydrophilic-lipophilic balance, amphiphilic moment, suitable hydrogen bond donors and acceptors are beneficial to the retention of enantiomers on the chiral stationary phase. Large differences of the hydrophilic regions at high energy levels, hydrophobic regions at low energy levels, amphiphilic moment, suitable hydrogen bond donors and acceptors, and anion regions between enantiomers are advantageous to the separation of enantiomers on the chiral stationary phase. These models allow the prediction of retention and separation factors, especially the elution order of enantiomers.%对手性化合物的保留因子和分离因子进行定量结构-特征关系(QSPR)研究，对于预测保留因子和分离因子甚至对映体的洗脱顺序都起着重要作用。本文选择手性二芳基甲烷衍生物为研究对象，采用VolSurf程序计算分子结构参数，并分别在其与保留因子以及分离因子间建立模型，采用测试集外部检验、留多法交叉验证和Y随机性检验等方法对分离因子模型的鲁棒性进行了评估，结果令人满意。对变量进行分析显示，分子的球形性，中等能级的亲水区、亲水-亲脂平衡、两亲矩、合适的氢键给体和受体均有利于异构体在手性固定相上的保留；一对对映体的高能级的亲水区、低能级的疏水区、两亲矩、合适的氢键给体和受体以及阴离子区之间大的差异对对映体在手性固定相上的分离是有利的。利用这些模型，可以轻松地预测对映体的保留因子和分离因子，甚至洗脱顺序。