Binding of Polychlorinated Biphenyls to the Aryl Hydrocarbon Receptor

Abstract

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Three-Dimensional Quantitative Structure-Activity Relationships of Dioxins and Dioxin-like Compounds: Model Validation and Ah Receptor Characterization

“…These results are consistent with research previously performed by Kafafi et al (27) on the entire congeneric series of chlorinated biphenyls. In this study, the authors presented a thermodynamic model based on lipophilic, electronic, and entropic characteristics for calculating the dissociation constants of ligand-receptor complexes.…”

Activation of the aryl hydrocarbon receptor by carbaryl: Computational evidence of the ability of carbaryl to assume a planar conformation

“…A significant amount of information suggests that the AhR can be bound and/or activated by chemicals for which the structural and physicochemical properties deviate from the defined structural requirements for AhR ligands [12, 13, 27, 31]. In line with this, our thorough computational study has shown that carbaryl preferentially takes a nonplanar conformation (CAR‐I).…”

“…The importance of planarity for AhR binding and CYP1A induction was exemplified by PCBs, from which congeners with para ‐ or meta ‐substitution, which can easily take a coplanar conformation, are potent CYP1A inducers, but ortho ‐substituted congeners, for which a coplanar conformation is energetically unfavorable, are weak or noninducers of CYP1A [9]. However, this statement has been questioned by several authors who determined, using computational studies, that some PCBs traditionally considered as AhR ligands are not coplanar molecules [12, 13]. In addition, it was found that some electrostatic properties (i.e., the dipole and quadrupole moments [14] and the electrostatic potential) were significant in rationalizing the effect on AhR.…”

The selective dietary accumulation of planar polychlorinated biphenyls in the otter (Lutra lutra)

“…Several authors have suggested that planar CBs are enriched in the aquatic food chain in comparison to nonplanar CBs, because planar CBs have a higher lipophilicity than similar nonplanar CBs [36]. Indeed, the depuration rate constants of planar CBs from mussels and oysters are lower than for other congeners with the same number of chlorine atoms [37,38].…”