Evaluation of the radical scavenging potency and mechanism of natural phenolamides: A DFT study

Phenolamides have received increasing interest owing to their diverse pharmacological activities and health benefits. However, the structure-antioxidant activity relationship and underlying mechanism are still largely unclear. Herein, thermodynamic and kinetic calculations based on density functional theory (DFT) were carried out to clarify the antioxidant effects and mechanisms of four aromatic monoamines conjugated phenolamides (AMCPs). The results show that solvent effect plays a crucial role in modulating the action mechanisms for the studied phenolamides. In non-polar media, the studied AMCPs prefer to trap radicals via the formal hydrogen atom transfer (fHAT) mechanism, while in polar solvents the radical-scavenging reaction proceeds via mixed mechanisms with sequential proton loss electron transfer (SPLET), sequential proton loss hydrogen atom transfer (SPLHAT) and sequential double proton loss electron transfer (SdPLET) depending on the pH of environments. 4 -OH in A-ring was found to be the preferred site to trap radical for CoTrp and CaTrp, while 5 '-OH in C-ring for CoSer and FeSer. Moreover, the representative compound CaTrp was predicted to has excellent HOO center dot scavenging potency (koverall = 3.15 x 108 M-1 s-1) in water at physiological pH, stronger than the two well-known anti-oxidants Trolox and ascorbic acid, and thus deserves to further utilization as nutraceutical or pharmaceutical candidates.