Nonenzymatic mechanisms of oxidation/reduction reactions of biologically important organic compounds.

摘要

Ascorbate acid, 2,3-dimethyl-1,4-hydroquinone and the vitamin E analogue Trolox normally oxidize by losing hydrogen atoms rather than electrons. Imidazole promotes oxidation of these compounds as assessed by cyclic voltammetry at pH 8.0. In the presence of a high concentration of imidazole, the oxidizing peaks of all three compounds are shifted toward lower potentials. By contrast, imidazole does not affect the cyclic voltammogram of methyl viologen, which undergoes electron rather than hydrogen-atom transfer. Imidazole is effective at pH 8.0 but only to a lesser extent at pH 5.5 indicating that it is the unprotonated form of imidazole that facilitates oxidation.;Imidazole and histamine also increase the rate of oxygen reduction by the biological organic reductants. Cyclic voltammogram data shows that imidazole and histamine affect the reductants rather than the potential of O2/O 2-·. This effect depends on the pH and concentration of imidazole or histamine. These results are consistent with the organic redox complex mechanism.;Dopamine oxidizes to an o-quinone especially at high pH. The dopamine side chain then inserts into the catechol ring forming a bicyclic compound, dopaminochrome. 4-Methylcatechol, a dopamine analogue that lacks the side-chain amine required for cyclization was studied. 4-Methylcatechol oxidizes in solution and adds H2O to form 4-methyl-1,2,5-trihydroxybenzene. This consumes O2 but is not inhibited by superoxide dismutase. Because the reduction potential of 4-methylcatechol is too high to reduce O2 to superoxide, O2 is most likely reduced by the 4-methylcatechol semiquinone formed by comproportionation of methylcatechol and the methylcatechol quinone. Aniline reacts quickly with the 4-methylcatechol quinone, eliminating it and halting formation of the semiquinone by comproportionation. Thus, methylcatechol oxidation in the presence of aniline requires superoxide. Superoxide is probably generated by reaction of the methylcatechol-aniline adduct with O2. These results suggest that cyclization of the dopamine quinone prevents the formation of other products such as 6-hydroxydopamine, the adduct formed by H2 O addition, and also the comproportionation of dopamine, which would facilitate oxidation.