HIGH RESOLUTION 1H NMR INVESTIGATIONS OF THE REACTIVITIES OF ALPHA -KETO ACID ANIONS WITH HYDROGEN PEROXIDE

The chemical reactivity of various a-keto acid anions (β hydroxypyruvate, β-phenylpyruvate, 2-ketobutyrate and 2-ketoglutarate) with hydrogen peroxide (H2O2) was investigated at physiological pH (7.4) and a temperature of 25°C. The initial concentration of the α-keto acid anions was kept constant at 1.00 mM whilst that of added H2O2 was varied from 0.25 to 1.00 mM, and the rate and extent of these reactions was evaluated using 1H NMR spectroscopy. At all H2O2 concentrations utilised, the order of reactivity of the α-keto acid anions was Shydroxypyruvate > β-phenylpyruvate > 2-ketobutyrate > 2-ketoglutarate. The results obtained are in agreement with a proposed mechanism for these reactions, involving nucleophilic attack of the mono-depro-tonated peroxide species (HO2-) at the C-2 carbonyl group carbon centre. The antioxidant capacity of such a-keto acids is discussed in terms of their potential use as therapeutic agents in clinical conditions where H2O2 has been shown to play a critical role in the diseas...