文摘
Redox active transition metals such as copper and iron contribute to biomacromoleculardamage that occurs during oxidative stress in a number of degenerative disorders and resultsin protein cross-linking. On the basis of suggestive evidence for an oxyradical-induced cross-linking between His and Lys side chains, we investigated the Cu(II)-catalyzed oxidation of4-alkylimidazoles in the presence of amines, as surrogates for these amino acid side chains,using ascorbic acid as a continual source of reducing equivalents. A model His-Lys cross-linkwas isolated and structurally characterized as a 5-alkyl-5-hydroxy-4-(alkylamino)-1,5-dihydroimidazol-2-one by NMR and mass spectrometry. Evidence that the 2-imidazolone, theprincipal oxidation product found in the absence of amine, is an intermediate in the formationof the imidazole-amine adduct was that higher yields of the cross-link adduct were obtainedstarting with the 2-imidazolone. Possible mechanisms for formation of the cross-link and otherobserved products are discussed.