BINDING OF SOME DIOXINS AND DIBENZOFURANS TO THE AH RECEPTOR - A QSAR MODEL-BASED ON COMPARATIVE MOLECULAR-FIELD ANALYSIS (COMFA)

Based on comparative molecular field analysis (CoMFA), a quantitative structure-activity relationship, model for the cytosolic aryl hydrocarbon (Ah) receptor binding affinity of 50 chlorinated dibenzo-para-dioxin and dibenzofuran analogues is presented. The electronic structures of these compounds were calculated using the semiempirical AM 1 method. Their extreme stabilities were rationalized using the frontier molecular orbital theory. The results indicate that their binding affinity was mainly influenced by steric and electrostatic interactions, whereas charge-transfer and hydrogen bonding mechanisms are probably of minor importance.