苯胺类化合物结构与毒性的密度泛函理论研究  

Study on the structure-toxicity relationship of aniline compounds by density functional theory

作　　者：顾云兰[1,2] 陈鑫[2] 简美玲[2] 

机构地区：[1]江苏省滩涂生物资源与环境保护重点建设实验室,江苏盐城224051 [2]盐城师范学院应用化学与环境工程研究所,江苏盐城224051

出　　处：《化学研究与应用》2015年第8期1139-1144,共6页Chemical Research and Application

基　　金：江苏省滩涂生物资源与环境保护重点建设实验室开放基金资助课题项目(JLCBE12009)资助;盐城师范学院自然科学研究项目(12YCKL004)资助

摘　　要：应用密度泛函理论(DFT)在杂化泛函B3LYP和基组6-311G(d,p)水平上对57个标题化合物进行结构优化,计算获得化合物的量化和理化参数,采用最佳变量子集回归构建了化合物对梨形四膜虫的毒性与描述符之间的定量结构-活性关系(QSAR)模型。所建最佳三元QSAR模型的复相关系数R2为0.915,留一法(leave-one-out,LOO)交互检验复相关系数Rcv2为0.891;用随机筛选出的19个预测集样本进行外部预测,所得外部预测集交互检验系数Qext2为0.821,QSAR模型具有较好的稳定性和较强的预测能力。模型结果表明影响毒性的主要因素有化合物最低空轨道能、正辛醇-水分配系数及最负非氢原子净电荷。对模型应用域(AD)进行了表征,所建模型可用于应用域内苯胺类化合物对梨形四膜虫毒性的预测。The geometrical structures of aniline compounds were optimized and the corresponding quantum-chemical and physicalchemical parameters were calculated using DFT/B3LYP procedure at 6-311 G （d, p）level. A reasonable QSAR equation for predicting the toxicities of aniline compounds to tetrahymena pyriformis was achieved with a quite high complex correlation coefficient（ R2 = 0.915 ）by leaps-and-bounds regression. The performance of the model was tested through cross-validation using leave-one-out procedure（LOO） and external validation with Rcv2and Qeat2 values of 0. 891,0. 821, respectively. The results showed that not only the QSAR model had good stability and predictability, but also the energy of the lowest unoccupied orbit（ ELUMO ） , the octanol-water partition coefficient（logP） and the most negative atomic net charge of molecule（q-） were the main factors affecting the toxicities of ani- line compounds. Moreover, the applicability domain of the developed model was assessed and visualized by the Williams plot. The developed QSAR model could be used to predict the toxicities of aniline compounds within the application domain to tetrahymena pyriformis.

关 键 词：苯胺类化合物 梨形四膜虫 最佳变量子集回归 密度泛函理论 定量构效关系 

分 类 号：O641[理学—物理化学]