A comparative analysis of the electrostatic potentials of some structural analogues of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin and of related aromatic systems

Abstract

AbstractWe have carried out an ab initio STO‐5G computational analysis of the electrostatic potentials of four structural analogues of the highly toxic 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) and four related aromatic systems benzo[a]pyrene, benz[a]anthracene, and two isomeric benzoflavones. These systems, to varying degrees, induce aryl hydrocarbon hydroxylase activity and are believed to interact with the same cytosolic receptor in initiating their biochemical responses. Our present results for the TCDD analogues support and have allowed us to further qualify our early observations regarding factors which are linked to high biological activities in the dibenzo‐p‐dioxins and structurally similar systems. We find that a high degree of activity appears to require nonoverlapping negative potentials above all or most of the lateral regions, with an observed optimum range of magnitudes. In systems with central oxygens, it is required that the negative oxygen potentials be small and weak; however, oxygen negative regions in the molecule are not necessary for high activity. The observed differences between the potential patterns of the four aromatic systems and those of TCDD and its active analogues may reflect an inherent dissimilarity in the nature of their interactions with the cytosolic receptor. That the carbonyl oxygen negative potential of 7,8‐benzoflavone is significantly more negative than its isomer's supports earlier speculation concerning the former's more effective inhibiting effects on metabolic oxidation.