NEW QSAR MODELS FOR POLYHALOGENATED AROMATICS

Electronic properties of polychlorinated dibenzo-p-dioxins (PCDDs), po lychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs), and polychlorinated diphenyl ethers (PCDEs) were calculated using the semi-empirical AM1 method. The calculated electronic descriptors - th e energy of the lowest unoccupied molecular orbital (E(LUMO)), the ene rgy of the highest occupied molecular orbital (E(HOMO)), the E(LUMO)-E (HOMO) gap (dE), and molecular polarizability - are related to the Ah receptor binding affinity values of PCDDs, PCDFs, and PCBs and immunot oxicity values for PCDEs. The quantitative structure-activity relation ships (QSARs) based on chlorine substitution patterns were also constr ucted, and they proved to be very predictive for Ah receptor binding. Significant correlations of the electronic factors were found between the dE and Ah receptor binding affinities for PCDDs, PCDFs, and PCBs a nd for immunotoxicity of PCDEs. A combination of descriptors E(LUMO) a nd the total number of chlorine atoms attached to a molecule (n(Cl)) g ives significant correlation for the Ah receptor binding of PCDFs and for immunotoxicity of PCDEs. Hydrophobicity values taken from the lite rature were shown to be nonsignificant for toxicity prediction of thes e polychlorinated compounds.