Study on the multiple mechanisms underlying the reaction between hydroxyl radical and phenolic compounds by qualitative structure and activity relationship

The activity–structure relationships (ASR) of phenolic compounds as hydroxyl-radical scavengers have mostly been studied and discussed with regard to their iron-chelating and hydrogen-donation properties in Fenton-type system, but extensive elucidation of multiple mechanisms underlying the hydroxyl radical scavenging reaction is out of obtaining up to now. In the present paper, a series of phenolic compounds was studied for their reactivity with hydroxyl radical by computed chemistry and deoxyribose degradation assay. The rate constant (K_S), an index dependent markedly on the reaction mechanism and intrinsic reactivity of antioxidants, was found to have good correlation with hydroxyl O–H bond strength (ΔH_f), electron-donating ability (ionization potential approximated by HOMO energy level), enthalpy of single electron transfer (E_a), and spin distribution of phenoxyl radicals (Ds^r) after H-abstraction. Moreover, the theoretical parameters were highly intercorrelated, suggesting that multiple mechanisms co-exist in the hydroxyl-radical-scavenging reaction and interact with each other. Multi-linear regression analysis indicated that, in addition to H-atom transfer, electron transfer process and stability of the resulted phenoxyl radicals also significantly influence the reactivity of quenching hydroxyl radicals. The QSAR model so established here was based on the elucidation of the complex molecular mechanisms, and may reasonably predict the antioxidant activity using simple experimental and calculated parameters.