The biological effects of most organophosphate compounds (OP) are arising by inhibition of the enzyme acetylcholinesterase (ACHE). The 3D-quantitative structure-activity relationship (3D-QSAR) on the acute toxicity to...The biological effects of most organophosphate compounds (OP) are arising by inhibition of the enzyme acetylcholinesterase (ACHE). The 3D-quantitative structure-activity relationship (3D-QSAR) on the acute toxicity to housefly (Musca nobulo L.) of 35 dialkyl phenyl phosphate compounds are studied by using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods, and the reaction mechanism between the OP and the AChE are discussed. In contrast to classical QSAR methods, CoMFA and CoMSIA, especially the combination of both approaches, can give more comprehensive and accurate perspectives on the mechanism of the reaction between OP and ACHE. The results show that the length of alkyl, and the electronegative of substituent on phenyl of OP have significant effects on the AChE activity,whereas, the hydrophobicity of OP has little influence. The steric and electronic properties of OP have a dominant influence on the reaction between OP and ACHE.展开更多
Optimized calculation of 35 dialkyl phenyl phosphate compounds (OPs) was carded out at the B3LYP/6-31G^* level in Gaussian 98 program. Based on the theoretical linear solvation energy relationship (TLSER) model, ...Optimized calculation of 35 dialkyl phenyl phosphate compounds (OPs) was carded out at the B3LYP/6-31G^* level in Gaussian 98 program. Based on the theoretical linear solvation energy relationship (TLSER) model, the obtained parameters were taken as theoretical descriptors to establish the novel QSPR model for predicting n-octanol/water partition coefficients (lgKow) of OPs. The new model achieved in this work contains three variables, i.e., molecular volume (Vm), dipole moment of the molecules (μ) and enthalpy (H^0). For this model, R^2 = 0.9167 and SD = 0.31 at large t values. In addition, the variation inflation factors (VIF) of variables are all close to 1.0, suggesting high accuracy of the predicting model. And the results of cross-validation test (q^2 = 0.8993) and method validation also showed the model of this study exhibited optimum stability and better predictive power than that from semi-empirical method. The model achieved can be used to predict IgKow of congeneric compounds.展开更多
文摘The biological effects of most organophosphate compounds (OP) are arising by inhibition of the enzyme acetylcholinesterase (ACHE). The 3D-quantitative structure-activity relationship (3D-QSAR) on the acute toxicity to housefly (Musca nobulo L.) of 35 dialkyl phenyl phosphate compounds are studied by using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) methods, and the reaction mechanism between the OP and the AChE are discussed. In contrast to classical QSAR methods, CoMFA and CoMSIA, especially the combination of both approaches, can give more comprehensive and accurate perspectives on the mechanism of the reaction between OP and ACHE. The results show that the length of alkyl, and the electronegative of substituent on phenyl of OP have significant effects on the AChE activity,whereas, the hydrophobicity of OP has little influence. The steric and electronic properties of OP have a dominant influence on the reaction between OP and ACHE.
基金the State Science Foundation of China (No. 20477018)
文摘Optimized calculation of 35 dialkyl phenyl phosphate compounds (OPs) was carded out at the B3LYP/6-31G^* level in Gaussian 98 program. Based on the theoretical linear solvation energy relationship (TLSER) model, the obtained parameters were taken as theoretical descriptors to establish the novel QSPR model for predicting n-octanol/water partition coefficients (lgKow) of OPs. The new model achieved in this work contains three variables, i.e., molecular volume (Vm), dipole moment of the molecules (μ) and enthalpy (H^0). For this model, R^2 = 0.9167 and SD = 0.31 at large t values. In addition, the variation inflation factors (VIF) of variables are all close to 1.0, suggesting high accuracy of the predicting model. And the results of cross-validation test (q^2 = 0.8993) and method validation also showed the model of this study exhibited optimum stability and better predictive power than that from semi-empirical method. The model achieved can be used to predict IgKow of congeneric compounds.