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Regioselective Deiodination of Iodothyronamines, Endogenous Thyroid Hormone Derivatives, by Deiodinase Mimics
Author(s) -
Mondal Santanu,
Mugesh Govindasamy
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201403248
Subject(s) - deiodinase , chemistry , iodothyronine deiodinase , triiodothyronine , decarboxylation , hormone , thyronine , dio2 , oxidative decarboxylation , medicine , thyroid , reverse triiodothyronine , endocrinology , enzyme , biochemistry , biology , catalysis
Abstract Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that play an important role in the activation and inactivation£ of thyroid hormones. It is known that iodothyronamines (TnAMs), produced by the decarboxylation of thyroid hormones, act as substrates for deiodinases. To understand whether decarboxylation alters the rate and/or regioselectivity of deiodination by using synthetic deiodinase mimics, we studied the deiodination of different iodothyronamines. The triiodo derivative 3,3′,5‐triiodothyronamine (T3 AM) is deiodinated at the inner ring by naphthyl‐based deiodinase mimics, which is similar to the deiodination of 3,3′,5‐triiodothyronine (T3). However, T3 AM undergoes much slower deiodination than T3. Detailed experimental and theoretical investigations suggest that T3 AM forms a weaker halogen bond with selenium donors than T3. Kinetic studies and single‐crystal X‐ray structures of T3 and T3 AM reveal that intermolecular I⋅⋅⋅I interactions may play an important role in deiodination. The formation of hydrogen‐ and halogen‐bonding assemblies, which leads to the formation of a dimeric species of T3 in solution, facilitates the interactions between the selenium and iodine atoms. In contrast, T3 AM, which does not have I⋅⋅⋅I interactions, undergoes much slower deiodination.