3D-QSAR/HQSAR-based analysis of bioconcentration and molecular modification of monophenyl aromatic compounds

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) of three-dimensional quantitative structure–activity relationship (3D-QSAR) models were conducted using 36 aromatic compound congeners as the training set and eight aromatic compound congeners as the test set. Logarithms ofexperimental bioconcentration data (logBCF) were used as dependent variables and the physicochemical properties ofthe aromatic compound congeners were used as independent variables. Furthermore, the molecular holographic quantitative structure–activity relationship (HQSAR) model constructed by the HQSAR module in Sybyl software was usedto establish a method to find molecular activity substitution sites of bioconcentration potential by coupling the moleculeactivity contribution map of HQSAR with the electrostatic contour map of CoMSIA. Pentachlorobenzene (PeCB) wasused as the target molecule to design PeCB derivatives with low bioconcentrations. Seven PeCB derivatives with lowbioconcentrations showed no significant changes in molecular toxicity and migration, while 5-NO2 -PeCB and six otherPeCB derivatives showed increased degradation abilities. By quantitative calculation using density functional theory,the flame retardancy and insulation properties of the PeCB derivatives were found to remain unchanged, except for thoseof 5-NO2 -PeCB.

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