物理化学学报 >> 2015, Vol. 31 >> Issue (1): 73-82.doi: 10.3866/PKU.WHXB201410281

理论与计算化学 上一篇    下一篇

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

胡桂香1, 骆成才1, 潘善飞2, 蒋勇军1, 邹建卫1   

  1. 1. 浙江大学宁波理工学院生物与化学工程学院, 浙江 宁波 315100;
    2. 浙江大学化学系, 杭州 310028
  • 收稿日期:2014-08-16 修回日期:2014-10-27 发布日期:2014-12-25
  • 通讯作者: 胡桂香 E-mail:hugx@nit.zju.edu.cn
  • 基金资助:

    国家自然科学基金(21002088, 21272211)和宁波市科技计划(2013D1003)资助项目

Predicting Retention and Separation Factors of Chiral Diarylmethane Derivates by QSPR Models

HU Gui-Xiang1, LUO Cheng-Cai1, PAN Shan-Fei2, JIANG Yong-Jun1, ZOU Jian-Wei1   

  1. 1. School of Biotechnology and Chemical Engineering, Ningbo Institute of Technology, Zhejiang University, Ningbo 315100, Zhejiang Province, P. R. China;
    2. Department of Chemistry, Zhejiang University, Hangzhou 310028, P. R. China
  • Received:2014-08-16 Revised:2014-10-27 Published:2014-12-25
  • Contact: HU Gui-Xiang E-mail:hugx@nit.zju.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (21002088, 21272211) and Programof Science and Technology of Ningbo, China (2013D1003).

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摘要：

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.

关键词: 手性, 分子建模, VolSurf, 二芳基甲烷, 偏最小二乘

Abstract:

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 lowenergy 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 allowthe prediction of retention and separation factors, especially the elution order of enantiomers.

Key words: Chirality, Molecular modeling, VolSurf, Diarylmethane, Partial least squares