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A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that the majority of PCBs are likely to interact with AhR in their nonplanar conformations. In addition, we demonstrate that the affinities of PCBs for AhR relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding toxic equivalency factors in animals. The reported methodology is likely to be applicable to other polyhalogenated and mixed polyhalogenated bi- and terphenyls and related xenobiotics; thus, it could minimize the number of in vivo studies in laboratory animals and facilitate the identification of potentially hazardous aromatic xenobiotics.Imagesp422-aFigure 2.

Results of experimental and theoretical studies of the properties and reactions of polycyclic aromatic aryl radicals are reported. Reactions of phenyl, 1-and 2-naphthalenyl, and 9-anthracenyl radicals with toluene and naphthalene were examined in the gas phase at 400 and 450 °C. Arylation rates for each radical were measured relative to hydrogen abstraction from

The dimerization energies of formamide and cis-N-methylacetamide (cis-NMA) are compared with those of the Ala and Gly dipeptides in their canonical β-sheet conformations using ab initio (SCF and MP2), density functional theory (DFT), and the SIBFA molecular mechanics procedure. Consistent with the gas-phase ab initio and DFT results, the SIBFA procedure is able to account for the larger dimerization energies of formamide and cis-NMA than of the dipeptides. In contrast, the majority of “conventional” force fields produced an inversion of the relative dimerization energies, giving rise to a more favorable dimerization of the Ala dipeptide than of cis-NMA (Beachy, M. D.; et al. J. Am. Chem. Soc. 1997, 119, 5908). Energy decomposition analysis on the dimers of formamide and the Gly dipeptide shows the Coulombic energy contribution to be the most important term favoring the formamide dimer. The analysis based on the SIBFA procedure similarly shows the multipolar energy term (E MTP) to be the most important contributor to this difference. This is due to its monopole−dipole and monopole−quadrupole components. The issue of the transferability of the multipolar expansion is discussed in the context of simulations of oligopeptides.