Electron Transfer Mechanisms in Antioxidant Activity

Electron transfer mechanisms lie at the heart of antioxidant action, governing how molecules intercept and neutralise reactive species. Primary pathways include hydrogen atom transfer, in which an antioxidant donates a hydrogen atom to a free radical; single electron transfer coupled to proton transfer, where an initial electron transfer is followed by proton donation; and sequential proton loss electron transfer, in which deprotonation precedes electron donation. The relative importance of these routes depends on molecular structure, redox potentials, solvent environment and pH. Computational studies employing density functional theory have revealed how bond dissociation enthalpies, ionisation potentials and proton affinities dictate reactivity. Experimental kinetics complement these findings by measuring rate constants for radical scavenging in lipid-like and aqueous media. Together, these insights inform the rational design of novel antioxidants for therapeutic and preservative applications, highlighting the global significance of modulating oxidative stress in biology, medicine and material science.

Research from Nature Portfolio

Recent theoretical investigations into flavonoid glycosides have shown that sugar conjugation alters both hydrogen atom transfer and sequential proton loss electron transfer pathways. Calculations in gas and solvent phases demonstrate that hydrogen atom transfer dominates in non-polar environments, while sequential proton loss electron transfer becomes thermodynamically preferred in polar solvents, with implications for dietary antioxidant efficacy. In parallel, in silico studies of natural lignans have identified benzylic hydrogen atoms as key sites for radical scavenging. They reveal that hydrogen atom transfer is favoured when benzylic C–H bonds are involved, whereas proton-coupled electron transfer prevails when phenolic O–H bonds act as the radical source. These findings provide molecular templates for designing antioxidants with tailored mechanistic profiles.

Electron Transfer Mechanisms in Antioxidant Activity publication trend

The graph below shows the total number of articles in electron transfer mechanisms in antioxidant activity across all publications each year (not limited to Nature Index journals).

Technical terms

Hydrogen atom transfer (HAT): Direct transfer of a hydrogen atom (proton plus electron) from an antioxidant to a radical species.

Single electron transfer (SET): Initial transfer of one electron from antioxidant to radical, often followed by proton transfer.

Sequential proton loss electron transfer (SPLET): Two-step process in which antioxidant first loses a proton, generating an anion that then donates an electron to a radical.

Electron transfer–proton transfer (ETPT): Electron transfer followed by a separate proton transfer event to complete radical quenching.

Bond dissociation enthalpy (BDE): Energy required to homolytically break a bond, indicating how readily an antioxidant can donate a hydrogen atom.

Density functional theory (DFT): Quantum mechanical method for calculating electronic energies, molecular geometries and thermodynamic parameters relevant to antioxidant mechanisms.

References

1. On the dual role of (+)-catechin as primary antioxidant and inhibitor of viral proteases. Computers in Biology and Medicine (2024).
2. Antioxidant Activity of Quercetin and Its Glucosides from Propolis: A Theoretical Study. Scientific Reports (2017).
3. Density functional theory study of the role of benzylic hydrogen atoms in the antioxidant properties of lignans. Scientific Reports (2018).
4. Current Trends in Computational Quantum Chemistry Studies on Antioxidant Radical Scavenging Activity. Journal of Chemical Information and Modeling (2022).
5. Computational Study of Ortho-Substituent Effects on Antioxidant Activities of Phenolic Dendritic Antioxidants. Antioxidants (2020).