Halogen Bonding in Biomimetic Deiodination of Thyroid Hormones and their Metabolites and Dehalogenation of Halogenated Nucleosides.

ABSTRACT

Thyroid hormones (THs) are key players in the endocrine system and play pivotal roles in carbohydrate and fat metabolism, protein synthesis, overall growth, and brain development. The thyroid gland predominantly produces thyroxine or 3,5,3',5'-tetraiodothyronine (T4) as a prohormone; three isoforms of a mammalian selenoenzyme-iodothyronine deiodinase (DIO1, DIO2 and DIO3)-catalyze the regioselective deiodination of T4 to produce biologically active and inactive metabolites. Whereas DIO1 catalyzes both 5- and 5'-deiodination of T4, DIO2 and DIO3 selectively mediate 5- and 5'-deiodination, respectively. In this review we discuss the regioselective deiodination of THs in the presence of organochalcogen compounds. Naphthalene-based compounds containing sulfur and/or selenium at the peri positions mediate regioselective 5-deiodination of THs, detailed mechanistic studies having revealed that the heterolytic cleavage of the C-I bond is facilitated by the formation of cooperative Se/S⋅⋅⋅I halogen bonds and Se/S⋅⋅⋅Se chalcogen bonds. We also discuss the biomimetic deiodination of several TH metabolites, including sulfated THs, iodothyronamines, and iodotyrosines. A brief discussion on the dehalogenation of halogenated nucleosides and nucleobases in the presence of organochalcogen compounds is also included.