Computational investigation of antioxidant activities and mechanisms of catechol analogues through a DFT study

Allyl-pyrocatechol and hydroxychavicol are catechol-type phenolic compounds from Piper betle that differ in the position of the allyl substituent, which may influence their electronic properties and antioxidant behavior. In this study, density functional theory (DFT) calculations were performed using the B3LYP functional with the 6-31 + G(2d,2p) basis set to investigate their frontier molecular orbital (FMO) characteristics and antioxidant mechanisms. Calculations were performed in gas and water phases using conductor-like polarizable continuum model (CPCM) solvation model. FMO analysis shows that hydroxychavicol exhibits a lower E_g in both phases (gas: 5.252 eV; water: 5.273 eV) compared to allyl-pyrocatechol (gas: 5.634 eV; water: 5.808 eV), suggesting relatively higher electronic reactivity and chemical softness. Solvent effects slightly increase the E_g of allyl-pyrocatechol, while hydroxychavicol remains relatively stable across phases. Thermodynamic evaluation indicates that formal hydrogen atom transfer (f-HAT) is more favorable in the gas phase based on bond dissociation enthalpy (BDE), whereas single electron transfer-proton transfer (SET-PT) is less competitive due to higher energetic requirements. In water phase, reduced ionization potential (IP) and proton affinity (PA) values suggest that solvation facilitates electron and proton transfer processes, making the sequential proton loss electron transfer (SPLET) pathway more relevant under polar conditions. Transition metal chelation (TMC), assessed via ΔH_acidity, indicates position-dependent deprotonation tendencies that may contribute as a secondary antioxidant pathway. Overall, hydroxychavicol is more potential reactive, while allyl-pyrocatechol is predicted relatively more stable.