Models for Oxygenases That Catalyze the Cleavage of Carbon-Carbon Bonds: Kinetics and Mechanism of the Decomposition of 2,3-Dimethyl-3-peroxyindolenines in Aqueous Solution

Article abstract of DOI:10.1021/ja00379a025

At 41 deg C in aqueous solution, 2,3-dimethyl-2-(hydroperoxy)indolenine (6) and 2,3-dimethyl-3-(methylperoxy)indolenine (7) react according to first-order kinetics to give, depending on pH, o-acetamidoacetophenone (8), 2,3-butanedione (biacetyl), or a mixture of the two in virtually quantitative yield.The pH-rate and product profiles obtained with 6 and 7 show some similarities but are not identical.With 7 as reactant the rate constant for formation of each product is characterized by a bell-shaped curve, the half-maximum points being at ca. pH 2.2 and 6 for biacetyl formation and at 6 and 7.5 for the formation of 8.Compound 6 reacts more rapidly and over a broader pH range; the overall ferst-order rate constant is at a maximum and relatively constant from pH 4 to 10, but it decreases at low and high pH.Above pH 7, 8 is the only product, but a mixture of 8 and biacetyl are formed at lower pHs.The pK_as of protonated 6 and 7 were found to be 2.28 and 2.18 respectively.Studies with 18O-labeled 6 indicate that at pH 4 8 is formed with essentially 100percent of the amide group labeled, but at higher pHs, the amount of unlabeled oxygen in this position increases to a maximum of 50percent at pHs 9 to 12.6.The results with 7 can be quantitatively rationalized in terms of a mechanism that involves cis and trans isomers of a carbinolamine (formed by hydration of 7) as important intermediates.Both geometric isomers can give biacetyl through a ring-opened intermediate that undergoes a carbon to oxygen migration of the aryl group.Only one geometric isomer can give 8, apparently by rapid decomposition of the alkoxide formed from the intermediate carbinolamine.The reaction of 6 is too complex to be able to fit the data quantitatively to a particular reaction mechanism, but qualitative considerations indicate that 8 can be formed from 6 by three different mechanisms that all seem to be competing under the reaction conditions.The relevance of these findings to related enzymic reactions is briefly considered.