Kinetic and mechanistic analyses of radical scavenging by 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid

In this study, we investigated the antioxidant mechanisms and efficiency of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid (A) and its derivative (B) via computational methods at the M05-2X/6-31G+(d) level. Our analysis, which is grounded in density functional theory and computational kinetics, reveals that the antioxidant activity of compound B is approximately 68 times greater than that of ascorbic acid (AsA) in polar environments, with rate constants indicating faster reaction times by an order of magnitude. Compound A also shows enhanced activity, albeit to a lesser extent. Specifically, compounds A and B exhibit rate constants of 1.49 × 10 8 and 1.61 × 10 8 M −1 s −1 , respectively, in terms of their ability to scavenge methylperoxyl radicals, whereas the corresponding rates are 2.56 × 10 6 M −1 s −1 for AsA. The structural analysis of compound B revealed that this enhanced activity was attributed to the introduction of tert-butyl groups at the ortho position of the phenolic hydroxyl group. This study also introduces kinetic parameters, including pKa values, branching ratios, and rate constants, for these derivatives, indicating that they are promising candidates for combating oxidative stress, with potential applications in pharmaceuticals and nutraceuticals.