- Regioselective deiodination of thyroxine by iodothyronine deiodinase mimics: An unusual mechanistic pathway involving cooperative chalcogen and halogen bonding
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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.
- Manna, Debasish,Mugesh, Govindasamy
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body text
p. 4269 - 4279
(2012/04/10)
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- A chemical model for the inner-ring deiodination of thyroxine by iodothyronine deiodinase
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The I of the beholder: The presented chemical model for the inner-ring deiodination of thyroxine (T4) and 3,5,3′-triiodothyronine (T3) by iodothyronine deiodinase (see scheme) highlights the importance of an in-built thiol group in proximity to the selenium atom. The effective removal of iodine in the case of T4 indicates that an enol-keto tautomerism is not required for deiodination. Copyright
- Manna, Debasish,Mugesh, Govindasamy
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scheme or table
p. 9246 - 9249
(2011/02/22)
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