Substituent-controlled phenoxy radical stabilization and HAT thermodynamics in small phenolic antioxidants: an ωB97X-D/CPCM molecular modeling study
Year: 2026
Type: preprint
Abstract: Context: Phenolic antioxidants are widely studied as small-molecule radical scavengers, but their apparent activity depends on the competition among hydrogen-atom transfer (HAT), sequential proton-loss electron transfer (SPLET), and single-electron transfer followed by proton transfer (SET-PT). In this context, the present work uses density functional molecular modeling to clarify how substituent pattern, phenoxy-radical stabilization, and medium effects control site-resolved antioxidant thermodynamics in eleven phenolic compounds, with caffeine and parent coumarin retained as non-phenolic electronic controls. Methods Geometry optimizations and harmonic frequency calculations were performed at the ωB97X-D/def2-SVP level, and gas- and solvent-phase single-point energies were refined at ωB97X-D/def2-TZVP using CPCM water, methanol, and benzene. Gibbs free energies were constructed as ESP + Gcorr, while absolute SPLET and SET-PT values used literature H + and e − free-energy constants. HAT was the lowest-energy pathway in all media. Caffeic acid OH1 showed the lowest ΔG HAT values in gas phase, water, methanol, and benzene (66.86, 69.60, 69.54, and 68.29 kcal mol − 1 , respectively). Spin-density, Mulliken, and NBO/NPA analyses linked favorable HAT to reduced O-centered spin localization and effective π-delocalization in phenoxy radicals. A focused M06-2X benchmark preserved the main ranking, supporting the robustness of the site-selectivity conclusion.
Source: Research Square
Institution: Cenderawasih University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7204256181