含硫苯衍生物对发光细菌生物毒性的QSAR研究

摘要

应用分子力学，半经验量子化学RM1方法，对29个含硫苯衍生物的几何构型进行全优化，将一系列的量子化学参数用于其结构和对发光细菌生物毒性的QSAR研究中．利用SPSS13．0软件，用多元逐步回归法建立了含硫苯衍生物对发光细菌毒性与量化参数的多元回归方程，结果表明，前线轨道能量差△E，辛醇／水分配系数（lgKow），取代基的Hammett电荷效应常数∑σ，碳原子C（6）上的静电荷E（6）及苯环上碳原子的静电之和∑，E对其生物毒性有明显的影响，其生物毒性可用下列模型来定量描述：lg（1／EC50）=10．238—0．009△E＋3．034E（6）＋2．108∑E-0．2921gKow＋0．522∑σ，N=29，R=0．930．%In this work,molecular mechanics and semi-empirical quantum chemistry RM1 methods were used to refine and optimize the geometry of 29 thiobenzene-containg derivartives and then the physicochemieal properties parameters,molecular parameters extracted from the geometric model along with indicator parameters were applied to establish the QSAR model for biological toxicity of thiobenzene-containg derivartives to photobacteria. Based on the multiple linear regression analysis,using software SPSS 13.0,equation was established between biological toxicity of thiobenzene-containing derivatives to photobacteria and the quantum chemical descriptors. The results indicate that biological toxicity of thiobenzene-containing derivatives to photobacteria was affected obviously by frontier orbital energy gap AE（ELuMO - EHOMo） ,Octanol/water Partition Coefficients（lg Kow）, Hammett charge effect constant（ , Electrostatic of C（6）E（6） as well as total electrostatic of benzene ring（∑E）. Then,we establish a QSAR model（lg（1/EC50） = 10.;238 - 0.009△E ＋ 3.034E（6） ＋ 2. 108 ∑σ - 0.2921g Kow ＋0.522∑σR = 0.930）with satisfactory results