Understanding the Reactivity of CO 3 ·- and NO 2 · Radicals toward S-Containing and Aromatic Amino Acids.

The reactivity of CO3 ·- and NO2 · radicals toward six amino acid side chains namely, cysteine (Cys), methionine (Met), phenylalanine (Phe), tyrosine (Tyr), histidine (His), and tryptophan (Trp), has been explored using state-of-art density functional theory (DFT) and transition state theory (TST). Three reaction mechanisms, namely hydrogen atom abstraction (HAT), radical adduct formation (RAF), and single electron transfer (SET), have been considered for detailed study. While CO3 ·- radical is highly reactive toward majority of amino acids, the reactivity of NO2 · radical is limited. The CO3 ·- radical creates oxidative damage to amino acid residues predominantly via HAT mechanism with moderate to high rate constant. Kinetic data suggest that tryptophan and tyrosine moiety possess the highest reactivity while the phenylalanine furnishes slow reaction. On the other hand, NO2 · radical cannot produce direct damage toward most of the amino acids except tryptophan and histidine. The NO2 · radical reacts exclusively by SET mechanism with 6.01 × 106 M-1 s-1 and 4.69 × 102 M-1 s-1 rate constant for Trp and His, respectively. Therefore, the CO3 ·- radical may cause severe damage to amino acid side chains during oxidative stress conditions, whereas the NO2 · radical is mostly inert. Moreover, the reaction of CO3 ·- and NO2 · radicals with amino acid radical intermediates generate variety of oxidation and nitro products which explain the formation of different experimentally characterized biomarkers during oxidative stress.