取代酚类化合物LC_(50)的QSAR模型建立与分析  

The buliding and analyse of QSAR models of LC_(50) of substituted phenol compounds

作　　者：彭艳芬[1] 王云[1] 刘小四[1] 刘天宝[1] 汪新[1] 

机构地区：[1]池州学院材料与化学工程系,安徽池州247000

出　　处：《计算机与应用化学》2015年第3期369-372,共4页Computers and Applied Chemistry

基　　金：国家自然科学基金资助项目(21271035);安徽省教育厅自然科学基金资助项目(KJ2013Z238);地方高校国家级大学生创新创业训练计划资助项目(201311306003;201211306025);安徽省大学生创新创业训练计划资助项目(AH201311306003)

摘　　要：基于定量结构.活性(QSAR)研究取代酚类化合物的急毒性具有重要意义。采用DFT-B3LYP方法,在较高基组6-311G^(**)水平下,全优化计算21种取代酚。从中获得分子最高占用和最低空轨道能(E_(HOMO)和E_(LUMO))、分子次最高占用和次最低空轨道能(E_(NHOMO)和E_(NLUMO))、分子总能量(E_T)、氢原子所带的最高正电荷(q_H^+)、最负非氢原子的静电荷(q^-)、分子偶极矩(μ)和分子体积(V)等描述符。结合文献中标题化合物对梨形四膜虫的毒性值(-lg LC_(50))和疏水性系数(10g Kow),由多元线性回归方法建成QSAR模型,采用内外双重验证的办法,深入分析和检验模型的稳健性。最佳模型的复相关系数(R^2),去一法(LOO)交替检验复相关系数(R_(cv)~2),外部预测样本复相关系数(R_(ext)~2)分别为0.924,0.922和0.830,故所建QSAR模型的稳定性和预测能力良好。由此推断,标题物对梨形四膜虫的毒性作用分为两步,首先穿过细胞壁在细胞内富集,以log Kow描述;其次与亲核试剂发生亲电反应,以点E_(NLUMO)表示。Study on quantitative structure-activity relationship （QSAR） of substituted phenol compounds would be helpful in researching for their acute toxieities. The DFT-B3LYP method, with the basis set 6-311G^＊＊, was employed to calculate the molecular geometries and electronic structures of 21 substituted phenol compounds. EHOMO, ELUMO, ENHOMO, ENLUMO, ET, qH^＋, q^-,μ~ and V were selected as structural descriptors. The acute toxicity （-Ig LC50） of these compounds to Tetrahymena pyriformis along with hydrophobieity described by log Kow, the above nine structural parameters, was used to established the quantitative structure-activity relationships （QSAR） by multiple linear regression. The estimation stability and generalization ability of the model was strictly analyzed by both internal and external validation. The correlation coefficient （R2）, leave-one-out （LOO） cross validation R2cv, predicted values versus experimental ones of external samples R^2ext of established the best model are 0.924, 0.922 and 0.830, respectively. These show that the QSAR model has both favorable estimation stability and good prediction capability. In light of the model, the toxic actions of organic compounds included two steps： one was the collection of the compounds in vivo, which was described by log Kow; the next was the electronic reactions between the chemicals and macromolecular compounds, which were represented by ENLUMO.

关 键 词：取代酚 密度泛函理论 定量构效关系 梨形四膜虫 

分 类 号：O641[理学—物理化学]