ELECTROCHEMICAL OXIDATION OF ENAMINES RELATED TO THE KEY INTERMEDIATE ON THIAMIN DIPHOSPHATE DEPENDENT ENZYMATIC PATHWAYS - EVIDENCE FOR ONE-ELECTRON OXIDATION VIA A THIAZOLIUM CATION RADICAL

Electrochemical experiments were performed in Me2SO on a number of 2-alkyl and 2-benzylthiazolium ions in the absence and presence of sodium bis(trimethylsilyl)amide (pK = 26). Under the latter conditions there is quantitative deprotonation at the C2± position leading to enamines that are structurally similar to the key enzyme-bound enamine intermediate present on all thiamin diphosphate dependent enzymes (Jordan, F.; Kudzin, Z. H.; Rios, C. B. J. Am. Chem. Soc. 1987, 109, 4415). For enamines derived from 2-alkylthiazolium salts in the presence of the strong base, but not in its absence, there was observed a cyclic voltammogram that is characteristic of irreversible processes. The relative peak potentials indicated that all enamines examined were easier to oxidize than ferrocene. The oxygen substituent at the C2± position facilitated oxidation compared to the hydrogen substituent by ca. 250 mV, and by ca. 120 mV compared to the methyl substituent. A series of para-substituted 2-(1-methoxy-1-phenylmethyl)thiazolium salts, when deprotonated at the C2± position, underwent reversible one-electron oxidation and gave a Hammett ρ = -7.61. The remarkably facile oxidation of all enamines was shown to proceed by a single-electron transfer according to controlled potential coulometry. The resulting cation radical undergoes dimerization according to spectroscopic analysis of the predominant product pursuant to electrolysis. Especially, the enamine derived from 2-(1-methoxyethyl)-3,4-dimethylthiazolium ion is a close analogue of the thiamin-bound intermediate. The results suggest that those enzymes responsible for oxidation at the C2± position may proceed by a stepwise redox mechanism via a thiazolium cation radical. These results constitute the first electrochemical determination of the redox properties of this key enamine intermediate and appear to have direct relevance to at least one enzymatic oxidative decarboxylation of pyruvic acid. pyruvate-ferrodoxin oxidoreductase, reported to proceed by a radical mechanism (Docampo, R.; Moreno, S. J.; Mason, R. P. J. Biol. Chem. 1987, 262, 12417). © 1990, American Chemical Society. All rights reserved.