title: Kinetic and thermodynamic aspects of the chain-breaking antioxidant activity of ascorbic acid derivatives in non-aqueous media.
abstract: Ascorbic acid (vit. C) is a cofactor whose reactivity toward peroxyl and other radical species has a key-role in its biological function. At physiological pH it is dissociated to the corresponding anion. Derivatives of ascorbic acid, like ascorbyl palmitate, are widely employed in food or in cosmetics and pharmaceuticals. While the aqueous chemistry of ascorbate has long been investigated, in non-aqueous media it is largely unexplored. In this work oxygen-uptake kinetics, EPR and computational methods were combined to study the reaction of peroxyl radicals with two lipid-soluble derivatives: ascorbyl palmitate and 5,6-isopropylidene-l-ascorbic acid in non-aqueous solvents. In acetonitrile at 303 K the undissociated AscH(2) form of the two derivatives trapped peroxyl radicals with k(inh) of (8.4 ± 1.0) × 10(4) M(-1) s(-1), with stoichiometric factor of ca. 1 and isotope effect k(H)/k(D) = 3.0 ± 0.6, while in the presence of bases the anionic AscH(-) form had k(inh) of (5.0 ± 3.3) × 10(7) M(-1) s(-1). Reactivity was also enhanced in the presence of acetic acid and the mechanism is discussed. The difference in reactivity between the AscH(2)/AscH(-) forms was paralleled by a difference in O-H bond dissociation enthalpy, which was determined by EPR equilibrations as 81.0 ± 0.4 and 72.2 ± 0.4 kcal mol(-1) respectively for AscH(2) and AscH(-) in tert-butanol at 298 K. Gas-phase calculations for the neutral/anionic forms were in good agreement yielding 80.1/69.0 kcal mol(-1) using B3LYP/6-31+g(d,p) and 79.0/67.8 kcal mol(-1) at CBS-QB3 level. EPR spectra of ascorbyl palmitate in tBuOH consisted of a doublet with HSC = 0.45 G centred at g = 2.0050 for the neutral radical AscH˙ and a doublet of triplets with HSCs of 1.85 G, 0.18 G and 0.16 G centred at g = 2.0054 for Asc˙(-) radical anion.
authors.affiliation: Department of Organic Chemistry A. Mangini, University of Bologna, Bologna, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Amorati
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Pedulli
authors.forename: Luca
authors.initials: L
authors.lastname: Valgimigli
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D018384:Oxidative Stress / Q000187:drug effects; D010545:Peroxides / Q000737:chemistry; D055471:Thermal Diffusion
chemical_list: D000975:Antioxidants; D010545:Peroxides; C049375:perhydroxyl radical; D001205:Ascorbic Acid