Ascorbate oxidation by iron, copper and reactive oxygen species: review, model development, and derivation of key rate constants

Ascorbic acid is among the most abundant antioxidants in the lung, where it likely plays a key role in the mechanism by which particulate air pollution initiates a biological response. Because ascorbic acid is a highly redox active species, it engages in a far more complex web of reactions than a typical organic molecule, reacting with oxidants such as the hydroxyl radical as well as redox-active transition metals such as iron and copper. The literature provides a solid outline for this chemistry, but there are large disagreements about mechanisms, stoichiometries and reaction rates, particularly for the transition metal reactions. Here we synthesize the literature, develop a chemical kinetics model, and use seven sets of laboratory measurements to constrain mechanisms for the iron and copper reactions and derive key rate constants. We find that micromolar concentrations of iron(III) and copper(II) are more important sinks for ascorbic acid (both AH₂ and AH⁻) than reactive oxygen species. The iron and copper reactions are catalytic rather than redox reactions, and have unit stoichiometries: Fe(III)/Cu(II) + AH₂/AH⁻ + O₂ → Fe(III)/Cu(II) + H₂O₂ + products. Rate constants are 5.7 × 10⁴ and 4.7 × 10⁴ M⁻² s⁻¹ for Fe(III) + AH₂/AH⁻ and 7.7 × 10⁴ and 2.8 × 10⁶ M⁻² s⁻¹ for Cu(II) + AH₂/AH⁻, respectively.