Prediction of hydroxylated metabolites in polychlorodibenzo-p-dioxins and polychlorodibenzofurans by Hückel molecular orbital calculations

Abstract

Hydroxylation either by mono- or di-oxygenases is the most common initial step in the metabolism of aromatic xenobiotic compounds by mammals and micro-organisms. From the observed metabolic patterns for polychlorodibenzo-p-dioxins (PCDD) and polychlorodibenzofurans (PCDF) it was shown that HMO calculations can predict the hydroxylated products derived from these compounds. The resistance of 2,3,7,8-tetrachlorodibenzo-p-dioxin and similarly substituted PCDDs towards enzymatic attack can be explained by the predicted lack of reactivity at positions 1, 4, 6, and 9 of the dibenzo-p-dioxin ring system. Influence of variations in the carbon skeleton and change in chlorine substitution on the level of HOMO energies are correlated with measured absorption of charge transfer complexes. Charge transfer properties of PCDD and PCDF probably play no role in difference of toxicities of various isomers.