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Amide‐Based Glutathione Peroxidase Mimics: Effect of Secondary and Tertiary Amide Substituents on Antioxidant Activity
Author(s) -
Bhabak Krishna P.,
Mugesh Govindasamy
Publication year - 2009
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200800483
Subject(s) - amide , moiety , chemistry , thiol , substrate (aquarium) , antioxidant , glutathione peroxidase , stereochemistry , medicinal chemistry , organic chemistry , catalase , oceanography , geology
Sec or terts: A series of sec ‐ and tert ‐amide substituted diselenides have been synthesised as synthetic mimics of glutathione peroxidase (GPx), characterized, and studied for their antioxidant activities using H 2 O 2 , Cum‐OOH, and t BuOOH as substrates and PhSH as thiol co‐substrate. The substitution at the free NH group of the amide moiety in the sec‐amide based diselenides is shown to enhance the GPx activity.A series of secondary and tertiary amide‐substituted diselenides were synthesized and studied for their GPx‐like antioxidant activities using H 2 O 2 , Cum‐OOH, and t BuOOH as substrates and PhSH as thiol co‐substrate. The effect of substitution at the free NH group of the amide moiety in the sec ‐amide‐based diselenides on GPx activity was analyzed by detailed experimental and theoretical methods. It is observed that substitution at the free NH group significantly enhances the GPx‐like activities of the sec ‐amide‐based diselenides, mainly by reducing the Se⋅⋅⋅O nonbonded interactions. The reduction in strength of the Se⋅⋅⋅O interaction upon introduction of N , N ‐dialkyl substituents not only prevents the undesired thiol exchange reactions, but also reduces the stability of selenenyl sulfide intermediates. This leads to a facile disproportionation of the selenenyl sulfide to the corresponding diselenide, which enhances the catalytic activity. The mechanistic investigations indicate that the reactivity of diselenides having sec ‐ or tert ‐amide moieties with PhSH is extremely slow; indicating that the first step of the catalytic cycle involves the reaction between the diselenides and peroxide to produce the corresponding selenenic and seleninic acids.