Effect of Molecular Structure on the Relative Hydrogen Peroxide Scavenging Ability of Some α-Keto Carboxylic Acids

• Published in: Journal of pharmaceutical sciences Vol. 105; no. 9; pp. 2879 - 2885
• Main Authors: Lopalco, Antonio, Stella, Valentino J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2016
• Subjects: Algorithms; antioxidant; Carboxylic Acids - chemistry; Carboxylic Acids - pharmacology; chemical stability; Chromatography, High Pressure Liquid; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; HPLC; hydrogen peroxide; Hydrogen Peroxide - chemistry; Hydrogen-Ion Concentration; Keto Acids - chemistry; Keto Acids - pharmacology; Kinetics; Molecular Structure; oxidation; pyruvic acid; Pyruvic Acid - chemistry; Pyruvic Acid - pharmacology; Spectrophotometry, Ultraviolet; structure reactivity; Structure-Activity Relationship; UV/Vis spectroscopy; α-keto carboxylic acid; antioxidant; chemical stability; α-keto carboxylic acid; hydrogen peroxide; structure reactivity; oxidation; kinetics; pyruvic acid; UV/Vis spectroscopy; HPLC
• DOI: 10.1016/j.xphs.2016.03.041
• ISSN: 0022-3549; 1520-6017

The α-keto carboxylic acid, pyruvic acid (1) was found to be a very effective peroxide scavenger but is subject to an aldol-like self-condensation/polymerization reaction. The purpose of this study was to evaluate the hydrogen peroxide, H2O2, scavenging ability of 3-methyl-2-oxobutanoic acid (2), 4-methyl-2-oxopentanoic acid (3), and 2-oxo-2-phenylacetic acid (phenylglyoxylic acid, 4) in the pH range 2-9 at 25°C and the effect of molecular structure on the relative reactivity. The reaction with H2O2 was followed by UV spectrophotometry at 220 or 260 nm and high-performance liquid chromatography. Pseudo-first order, buffer-independent decarboxylation kinetics were observed in the presence of molar excess H2O2. The second-order rate constants for 2-4 followed a sigmoidal shape and mechanism similar to pyruvic acid. Pyruvic acid was a superior H2O2 scavenger to 2-4 over the pH range 2-9 but 4 was more reactive than 2 and 3 at pH values above 6. There was a qualitative correlation between the degree of keto-group hydration and reactivity of the acids in the pH range 4-6 while the data above pH 7 suggested that the intrinsic decarboxylation step for 4 was faster than for pyruvic acid. Differences in reactivity to molecular structure were analyzed.