4604-41-5Relevant articles and documents
Deiodination of thyroid hormones by iodothyronine deiodinase mimics: Does an increase in the reactivity alter the regioselectivity?
Manna, Debasish,Mugesh, Govindasamy
, p. 9980 - 9983 (2011)
Organoselenium compounds as functional mimics of iodothyronine deiodinase are described. The naphthyl-based compounds having two selenol groups are remarkably efficient in the inner-ring deiodination of thyroxine. The introduction of a basic amino group in close proximity to one of the selenol moieties enhances the deiodination. This study suggests that an increase in the nucleophilic reactivity of the conserved Cys residue at the active site of deiodinases is very important for effective deiodination.
Remarkable Effect of Chalcogen Substitution on an Enzyme Mimetic for Deiodination of Thyroid Hormones
Raja, Karuppusamy,Mugesh, Govindasamy
supporting information, p. 7674 - 7678 (2015/06/25)
Iodothyronine deiodinases are selenoenzymes which regulate the thyroid hormone homeostasis by catalyzing the regioselective deiodination of thyroxine (T4). Synthetic deiodinase mimetics are important not only to understand the mechanism of enzyme catalysis, but also to develop therapeutic agents as abnormal thyroid hormone levels have implications in different diseases, such as hypoxia, myocardial infarction, critical illness, neuronal ischemia, tissue injury, and cancer. Described herein is that the replacement of sulfur/selenium atoms in a series of deiodinase mimetics by tellurium remarkably alters the reactivity as well as regioselectivity toward T4. The tellurium compounds reported in this paper represent the first examples of deiodinase mimetics which mediate sequential deiodination of T4 to produce all the hormone derivatives including T0 under physiologically relevant conditions.
Regioselective deiodination of thyroxine by iodothyronine deiodinase mimics: An unusual mechanistic pathway involving cooperative chalcogen and halogen bonding
Manna, Debasish,Mugesh, Govindasamy
supporting information; experimental part, p. 4269 - 4279 (2012/04/10)
Iodothyronine deiodinases (IDs) are mammalian selenoenzymes that catalyze the conversion of thyroxine (T4) to 3,5,3′-triiodothyronine (T3) and 3,3′,5′-triiodothyronine (rT3) by the outer- and inner-ring deiodination pathways, respectively. These enzymes also catalyze further deiodination of T3 and rT3 to produce a variety of di- and monoiodo derivatives. In this paper, the deiodinase activity of a series of peri-substituted naphthalenes having different amino groups is described. These compounds remove iodine selectively from the inner-ring of T4 and T3 to produce rT3 and 3,3′-diiodothyronine (3,3′-T2), respectively. The naphthyl-based compounds having two selenols in the peri-positions exhibit much higher deiodinase activity than those having two thiols or a thiol-selenol pair. Mechanistic investigations reveal that the formation of a halogen bond between the iodine and chalcogen (S or Se) and the peri-interaction between two chalcogen atoms (chalcogen bond) are important for the deiodination reactions. Although the formation of a halogen bond leads to elongation of the C-I bond, the chalcogen bond facilitates the transfer of more electron density to the C-I σ* orbitals, leading to a complete cleavage of the C-I bond. The higher activity of amino-substituted selenium compounds can be ascribed to the deprotonation of thiol/selenol moiety by the amino group, which not only increases the strength of halogen bond but also facilitates the chalcogen-chalcogen interactions.
