Amide-based glutathione peroxidase mimics: effect of secondary and tertiary amide substituents on antioxidant 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 tBuOOH 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.
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012 (India), Fax: (+91) 80-2360 1552/2360 0683.
Krishna P
KP
Bhabak
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012 (India), Fax: (+91) 80-2360 1552/2360 0683.
Govindasamy
G
Mugesh
D000577:Amides / Q000737:chemistry*; D000975:Antioxidants / Q000378:metabolism; D032701:Biomimetics; D002264:Carboxylic Acids / Q000737:chemistry; D002384:Catalysis; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D016566:Organoselenium Compounds / Q000737:chemistry
D000577:Amides; D000975:Antioxidants; D002264:Carboxylic Acids; D016566:Organoselenium Compounds; C473453:seleninic acid; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase