Oxidation of Acid, Base, and Amide Side-Chain Amino Acid Derivatives via Hydroxyl Radical.

Hydroxyl radical (• OH) is known to be highly reactive. Herein, we analyze the oxidation of acid (Asp and Glu), base (Arg and Lys), and amide (Asn and Gln) containing amino acid derivatives by the consecutive attack of two • OH. In this work, we study the reaction pathway by means of density functional theory. The oxidation mechanism is divided into two steps: (1) the first • OH can abstract a H atom or an electron, leading to a radical amino acid derivative, which is the intermediate of the reaction and (2) the second • OH can abstract another H atom or add itself to the formed radical, rendering the final oxidized products. The studied second attack of • OH is applicable to situations where high concentration of • OH is found, e.g., in vitro. Carbonyls are the best known oxidation products for these reactions. This work includes solvent dielectric and confirmation's effects of the reaction, showing that both are negligible. Overall, the most favored intermediates of the oxidation process at the side chain correspond to the secondary radicals stabilized by hyperconjugation. Intermediates show to be more stable in those cases where the spin density of the unpaired electron is lowered. Alcohols formed at the side chains are the most favored products, followed by the double-bond-containing ones. Interestingly, Arg and Lys side-chain scission leads to the most favored carbonyl-containing oxidation products, in line with experimental results.