QSAR MODEL FOR THE PREDICTION OF THE HALF LIFE OF POLYCHLORINATED BIPHENYLS IN HUMANS
Keywords:PCBs, half life, atomic charge, congener, QSAR, molecular descriptor.
AbstractThe elimination rate of the polychlorinated biphenyls (PCBs) in humans is of great environmental
importance, as represented by their half-lives (t1/2). Based on the literature, a database of this toxickinetic variable for PCBs in humans is elaborated. 14 PCB structures with known half-lives are
optimized, making a previous scan of the dihedral angle between the two phenyl rings, using AM1 to
find the most stable conformation. Substituted mono-orto PCBs present an approximate dihedral
angle of 120°, and the substituted poly-orto of 90°. Several descriptors are calculated from optimized structures using B3LYP/6-31G**. The molecular descriptors are associated with the t1/2 values by multiple lineal regression analysis. This reveals that the t1/2 of PCBs is a function of the sum of atomic charges on the chlorine atoms (åQCl) and the sum of atomic charges for the carbon atoms in metaposition (ΣQC-meta). The regression coefficient value of the prediction model is 0.84, and the Pvalue is <0.01 (range: 1.2-24 years). A discriminant analysis allows to verify the molecular characteristics that describe best the t1/2 of PCBs. The discrimination function carried out for two groups, finds that the descriptor ΣQC-meta is the most important to classify the PCBs according to their t1/2. Taking in account that the metabolism of PCBs depends on the substitution of the carbon atoms in meta-para positions, since this begins with the formation of an epoxy-PCB in these atoms of the biphenyls, the electronic descriptor ΣQC-meta can explain this local chemical environment and the metabolic susceptibility of the congener to degradation by cytochrome P450 isozymes (CYPs).
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