Regioselective Deiodination of Thyroxine by Iodothyronine Deiodinase Mimics: An Unusual Mechanistic Pathway Involving Cooperative Chalcogen and Halogen Bonding
Data(s) |
07/03/2012
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Resumo |
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. |
Formato |
application/pdf application/pdf text/plain text/plain text/plain |
Identificador |
http://eprints.iisc.ernet.in/44345/1/Regioselective.pdf http://eprints.iisc.ernet.in/44345/2/Supporting_ionformation_for.pdf http://eprints.iisc.ernet.in/44345/3/om201244a_si_002.cif http://eprints.iisc.ernet.in/44345/4/ja210478k_si_004.cif http://eprints.iisc.ernet.in/44345/5/ja210478k_si_005.cif 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. |
Publicador |
American Chemical Society |
Relação |
http://pubs.acs.org/doi/abs/10.1021/ja210478k http://eprints.iisc.ernet.in/44345/ |
Palavras-Chave | #Inorganic & Physical Chemistry |
Tipo |
Journal Article PeerReviewed |