Computational Study of the Peroxyl Radical Scavenging Ability of Phenolic Antioxidants

The physiological implications of chronic oxidative stress motivate research on antioxidant activity: the cellular defence and repair mechanism for oxidative damage. Through evaluation of thermodynamic and kinetic quantities of hydroperoxyl (•OOH) and methylperoxyl (•OOCH3) radical scavenging reactions, the primary antioxidant activity of twenty phenolic compounds, previously investigated for tertiary antioxidant activity, is evaluated at the M06-2X(SMD)/6-31++G(d,p) level of theory in water and pentyl ethanoate. The formal-hydrogen atom transfer (f-HAT) and single electron transfer (SET) mechanisms are considered. In aqueous environments, SET proves to be the dominant mechanism for most phenols studied, as nearly half of the phenols produced rate constants within the diffusion limit, implicating biochemical relevance. Only three of the phenols also exhibited significant activity via f-HAT. The phenols show greater SET scavenging of •OOH than •OOCH3, but the more efficient f-HAT target is variable. Through comparison with their tertiary activity, we show that thermodynamics are a better predictor for antioxidant activity when the radical is a less complex species (i.e., •OOH versus protein radical); however, several inconsistencies in the Bell–Evans–Polanyi principle still appear between and within solvents and phenolic compounds. This work examines the differences that appear when studying primary versus tertiary antioxidant activity and highlights the importance of using kinetic strategies to investigate antioxidant activity.