Halogen Bonding Interactions of Haloaromatic Endocrine Disruptors and the Potential for Inhibition of Iodothyronine Deiodinases

Abstract

Halogen bonding (XB) is a potential mechanism for the inhibition of the thyroid‐activating/deactivating iodothyronine deiodinase family of selenoproteins through interactions with halogenated endocrine disrupting compounds (EDCs). Trends in XB interactions were examined using density functional theory for a series of polyhalogenated dibenzo‐1,4‐dioxins, biphenyls, and other EDCs with methylselenolate, a simple model of the Dio active site selenocysteine. The strengths of the interactions depend upon the halogen (Br>Cl), the degree of substitution, and the position of the acceptor. In terms of donor‐acceptor energies, interactions at the meta position are often the strongest, suggesting a link to the topology of THs, especially for outer‐ring deiodination of thyroxine, which occurs at a meta iodine, and produces the active TH. However, relationships between XB interaction strengths and potential for Dio inhibition should be made in the context of the binding to the active sites, the topology of which are not fully characterized.