Oxidative stress is a biological process that has been linked to many diseases; hence, understanding its prevention and repair is essential in medicine. This study focuses on the repair of damaged leucine as a lateral chain in a protein environment simulated by N-formyl leucinamide by a group of 13 phenolic antioxidants with a single reaction site. Hydrogen atom transfer (HAT) and single electron transfer (SET) were the repair reactions studied thermodynamically and kinetically at the M06-2X(SMD)/6-31++G(d,p) level of theory in pentyl ethanoate and water at physiological pH. These solvents simulate the lipidic and aqueous media that a damaged protein may be exposed to.

The SET repair reactions were very endergonic and had small rate constants, which indicates their lack of biological relevance. This result is also influenced by the high aqueous pKa values of these antioxidants. All HAT reactions were very exergonic and, in general, it was found that the more exergonic the reaction the larger its rate constant, as stated by the Bell-Evans-Polanyi principle. However, for several repair reactions this principle was violated, which shows the need for computational kinetics studies to properly assess the tertiary antioxidant activity of a species.

The rate constants for the HAT repair reactions were found to be δ > β > γ. From these results, the antioxidant activity of 7 polyphenolic compounds was also investigated by considering the fastest repair reaction found (the δ HAT repair in pentyl ethanoate). Some of the HAT reactions studied had rate constants in the diffusion limit which indicates their biological relevance.