The scavenging mechanism of hydrazone compounds towards HOO˙ and CHOO˙ radicals: a computational mechanistic and kinetic study.

In this study, a detailed DFT investigation was conducted to systematically analyze the scavenging activity of six hydrazone compounds (1-6) against HOO˙ and CHOO˙ radicals. Three mechanistic pathways were explored: hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SETPT), and sequential proton loss electron transfer (SPLET). These mechanisms were evaluated based on thermodynamic parameters, including bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA), and electron transfer enthalpy (ETE) in the gas phase, water, and pentyl ethanoate. HAT was identified as the most favorable mechanism in the gas phase, while SPLET was preferred in water. Among the studied compounds, compound 2 showed the highest rate constants for HOO˙ scavenging following the HAT mechanism in the gas phase observed at the O2'-H bond with a value of 6.02 × 10 M s. For CHOO˙ scavenging, the same compound exhibited the highest rate constants at the N8-H (9.03 × 10 M s) and O2'-H (7.22 × 10 M s) sites. The calculated overall rate constant values of compound 2 are (HOO˙) = 6.86 × 10 M s and (CHOO˙) = 1.63 × 10 M s. These results suggest that compound 2 exhibits antioxidant activities comparable to butylated hydroxyanisole (BHA), consistent with experimental findings, indicating its potential as an effective scavenger of hydroperoxyl and methoxy peroxyl radicals. In aqueous solution, the anionic form of compound 2 showed the greatest HOO˙ and CHOO˙ radical scavenging activity among all of the studied compounds with rate constants of = 1.8 × 10 M s and = 3.3 × 10 M s, respectively. Compared with some typical antioxidants such as rubiadin, natural fraxin, and natural anthraquinones, compound 2 showed higher HOO˙ and CHOO˙ radical scavenging activity in water. Thus, compound 2 is a promising antioxidant in aqueous physiological environments.