取代芳烃对大型蚤急性毒性的定量构效关系研究

目的]建立具有良好相关性和稳定性的取代芳烃对大型蚤定量结构-活性关系（QSAR）模型。方法]采用Gaussian03程序包中密度泛函理论（DFT）B3LYP方法计算取代芳烃的部分结构参数和毒性参数。结果]-lgEC50的回归方程为-lgEC50=4.496＋1.5×10-2MM＋9.958×EHOMO＋0.677×ΔQR;方程中各自变量的变异膨胀因子（VIF）分别为：1.508、1.364和1.157。取代芳烃对大型蚤急性毒性的主要影响因子为分子量MM、分子最高占有轨道能EHOMO和苯环上净电荷增量ΔQR,且这3个结构参数与-lgEC50正相关,其标准系数分别为0.986、0.289和0.175。分子量越大,分子总能量（能量为负值）越低,化合物越稳定,毒性越大;分子量越大,lgP越大,化合物的脂溶性越大,毒性越大。结论]该试验建立的模型具有良好的稳定性和很强的预测能力。

Study on the Quantitative Structure-activity Relationship of Acute Toxicities of Substituted Aromatic Compounds to Daphnia magna

Objective] The study aimed to establish the quantitative structure-activity relationship (QSAR) model of substituted aromatic compounds to Daphnia magna,which had good relativity and stability. Method] The partial structure parameters and toxicity parameters of substituted aromatic compounds were calculated out by using density functional theory (DFT) B3LYP method from Gaussian03 software package. Result] The regression equation of-lgEC50 was-lgEC50 = 4.496 + 1.5 × 10-2MM + 9.958 × EHOMO + 0.677 × ΔQR; the variance inflation factors (VIF) of independent variables in the equation were 1.508,1.364 and 1.157 resp. The main influencing factors of acute toxicity of substituted aromatic compounds to D. magna were molecular weight MM,energy of highest occupied molecular orbital (EHOMO) EHOMO and net charge increment on benzene ring ΔQR,these 3 structure parameters was positively related to-lgEC50 and their standard coefficients were 0.986,0.289 and 0.175 resp. The bigger the molecular weight was,the lower its total energy (the energy was negative value) was,the more stable the compound was and the stronger its toxicity was; the bigger the molecular weight was,the bigger the lgP was,the better the fat-solubility of compound was and the stronger its toxicity was. Conclusion] The model established in this experiment had good stability and very strong prediction ability.