ePrints@IIScePrints@IISc Home | About | Browse | Latest Additions | Advanced Search | Contact | Help

Regioselective Deiodination of Thyroxine by Iodothyronine Deiodinase Mimics: An Unusual Mechanistic Pathway Involving Cooperative Chalcogen and Halogen Bonding

Manna, Debasish and Mugesh, Govindasamy (2012) Regioselective Deiodination of Thyroxine by Iodothyronine Deiodinase Mimics: An Unusual Mechanistic Pathway Involving Cooperative Chalcogen and Halogen Bonding. In: Journal of the American Chemical Society, 134 (9). pp. 4269-4279.

[img] PDF
Regioselective.pdf - Published Version
Restricted to Registered users only

Download (2403Kb) | Request a copy
[img] PDF
Supporting_ionformation_for.pdf - Supplemental Material
Restricted to Registered users only

Download (2688Kb) | Request a copy
[img] Plain Text
om201244a_si_002.cif - Supplemental Material
Restricted to Registered users only

Download (33Kb) | Request a copy
[img] Plain Text
ja210478k_si_004.cif - Supplemental Material
Restricted to Registered users only

Download (24Kb) | Request a copy
[img] Plain Text
ja210478k_si_005.cif - Supplemental Material
Restricted to Registered users only

Download (4Kb) | Request a copy
Official URL: http://pubs.acs.org/doi/abs/10.1021/ja210478k

Abstract

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 pen-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 pen-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 pen-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 sigma* 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.

Item Type: Journal Article
Additional Information: Copy right of this article belongs to American Chemical Society.
Department/Centre: Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited: 25 Apr 2012 08:31
Last Modified: 25 Apr 2012 08:33
URI: http://eprints.iisc.ernet.in/id/eprint/44345

Actions (login required)

View Item View Item