Molecule Modification And Performance Of Polychlorinated Phenols By 3D-QSAR Technology

Three-dimensional quantitative structure-activity relationship(3D-QSAR)models were established by comparative molecular field analysis(CoMFA)and comparative molecular similarity indices analysis(CoMSIA).Experimental toxicity data in Poecilia reticulata(pLC50)and physico-chemical properties for 12 polychlorinated phenols were used as dependent and as independent variables,respectively.Among the 12 polychlorinated phenols,nine were randomly selected and used as a training set,and the other three polychlorinated phenols were used as a test set.Pentachlorophenol(PCP),which is the most toxic among the 20 polychlorinated phenols used in this experiment,was selected as an examplefor modification using contour maps produced using the established 3D-QSAR models.The insecticidal effect,biodegradation and bioconcentration of the new designed molecules were verified through the related 3D-QSAR model.The result showed that the 3D-QSAR electrostatic contour maps were used to modify PCP and design 11 new compounds with lower toxicity.The effectiveness of each of these molecules as a pesticide was verified using a 3D-QSAR model for polychlorinated phenol toxicity against Tetrahymena pyriformis.Four of these compounds,with-Br,-I,-OH and-NH2 groups in place of chlorine at the 3-position on PCP,were all at least as effective as PCP against T.Pyriformis.The first-order rate constants(Kb)of these four compounds were predicted using a 3D-QSAR model for polychlorinated phenol degradation,which showed they were more biodegradable than PCP.Furthermore,a 3D-QSAR model for polychlorinated phenols bioconcentration in fish(containing Poecilia reticulata,Oncorhynchus mykiss,Pimephales promelas and Oryzias latipes)showed that there was no significant difference between the bioconcentration factors of the four new compounds and that of PCP.The results obtained are hoped to provide a new route for lowering the POPs characteristics of those polychlorinated phenol homologues and derivatives in use.