Structure-Antioxidant Activity Relationship of Hydroxycinnamic Acid Derivatives: A Computational Study

Cinnamic acid derivatives (ferulic acid (FA), isoferulic acid (IFA), m/p-coumaric acid (MCA/ PCA)) are frequently occurring in plants, and used in food, cosmetics and diverse therapeutic indications.The antioxidant activity of these derivatives, including guaiacol (GO), was investigated in the gas phase and in different solvents using B3LYP/6-31++G(d,p) level of theory.In this study, several mechanisms involving electron and proton transfers, including hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SETPT), Sequential Proton Loss Electron Transfer (SPLET), and Sequential Proton Loss Hydrogen Atom Transfer (SPLHAT), double HAT (dHAT) and others were systematically examined.The HAT and dHAT are identified as the main radical-scavenging mechanisms in aqueous media, as evidenced by their lower energy requirement compared to other methods such as SETPT and SPLET.Lower BDE3 values for the anionic species favoured the SPLHAT mechanism over SETPT and SPLET.The presence of guaiacyl units allows strong radical-scavenging performance via dHAT mechanisms.The absence of a methoxy group in PCA and MCA increases the BDE compared to FA and IFA.The side chain has a negligible effect on IP (FA vs GO), whereas methoxy substitution reduces IP but increases PDE in FA, IFA, and GO relative to PCA and MCA.The electron donation index indicates a strong electron donor potential, whereas the electron-accepting index suggests poor electron-acceptor ability of these compounds.Additionally, the activation energies for HAT by the HOO• radical show that FA and GO follow similar trends and are both kinetically and thermodynamically more favourable than the other molecules.