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.
Bhabak
Krishna P
KP
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012 (India), Fax: (+91) 80-2360 1552/2360 0683.
Mugesh
Govindasamy
G
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012 (India), Fax: (+91) 80-2360 1552/2360 0683.
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