Light-Induced Oxidation of Tryptophan and Histidine. Reactivity of Aromatic N-Heterocycles toward Triplet-Excited Flavins

Mechanisms of flavin-mediated photooxidation of electron-rich amino acids tryptophan and histidine were investigated for aqueous solutions. Indole, representing the tryptophan side chain in proteins, reacted at nearly diffusion controlled rates (k ∼ 2.7 × 109 L mol−1 s−1 at 293 K) with the triplet-excited flavin state, but reactions of imidazole (and histidine) were significantly slower (k < 2.0 × 108 L mol−1 s−1) as determined by laser flash photolysis. Oxidation rates of derivates were invariably susceptible to electronic factors affecting incipient radical cation stability, while no primary kinetic hydrogen/deuterium isotope effect was observed for imidazole. Thus reaction by electron transfer was proposed in contrast to a direct hydrogen abstraction. Unlike indole compounds, imidazole derivatives suffered from the presence of a basic imino nitrogen (═N−), which caused the rate constant of histidine free base (k ∼ 1.8 × 108 L mol−1 s−1) to drop considerably upon protonation. Complexation of the imino n...