Reactions of the Wurster's blue radical cation with thiols, and some properties of the reaction products

Formation of 1-electron oxidation products of aromatic amines in biological systems have been ascertained. The mechanisms of the toxic actions of the aminyl radicals and their corresponding detoxication reactions are much less established. During the studies of reactions of GSH with the N,N,N',N'-tetramethyl-p-phenylenediamine radical cation (TMPD) (Wurster's blue) two pathways were detected: (1) a slow second order reaction (k = 5 M-1.s-1) which gave the parent amine and (ultimately) GSSG, and (2) a fast, complex reaction which yielded 2-(glutathione-S-yl)-N,N,N',N'-tetramethyl-p-phenylenediamine (2-GS-TMPD). From kinetic reasons, this reaction was suggested to be composed of a rapid disproportionation reaction followed by a reductive 1,4-Michael-addition. This reaction pathway prevailed at GSH concentrations below 1 mM. At higher GSH concentrations formation of the thioether was suppressed. This hypothesis was confirmed when the reaction of the highly labile N,N,N',N'-tetramethyl-p-quinonediiminium dication (TMQDI++) with GSH was followed: In this case, thioether formation outweighed clearly reductive mechanisms, the latter yielding ultimately the amine and GSSG. Similar to N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), 2-GS-TMPD was also capable of producing ferrihemoglobin in a catalytic reaction. Its rate, however, was only 3% that observed with the parent amine. During this reaction the thioether was apparently oxidized to the corresponding quinonediiminium dication, which gave the corresponding quinonemonoimine on acidification.