title: Effect of Molecular Structure on the Relative Hydrogen Peroxide Scavenging Ability of Some α-Keto Carboxylic Acids.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopalco
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047. Electronic address: stella@ku.edu.
authors.forename: Valentino J
authors.initials: VJ
authors.lastname: Stella
mesh_terms: D000465:Algorithms; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007651:Keto Acids / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D015394:Molecular Structure; D019289:Pyruvic Acid / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D016166:Free Radical Scavengers; D007651:Keto Acids; D019289:Pyruvic Acid; D006861:Hydrogen Peroxide
keywords: HPLC; UV/Vis spectroscopy; antioxidant; chemical stability; hydrogen peroxide; kinetics; oxidation; pyruvic acid; structure reactivity; α-keto carboxylic acid