Ferulic Acid as a Spin Trap: Computational Studies of Hydroxyl Radical Stabilization

Ferulic acid (FA) is a naturally occurring phenolic antioxidant that has been proposed as a potential spin-trapping framework for hydroxyl radicals (•OH). However, the relative thermodynamic stability of FA–OH radical adducts has not been systematically evaluated using high-level quantum chemical methods. In this study, geometry optimizations and harmonic vibrational frequency analyses were performed at the Hartree–Fock (HF) and Density Functional Theory (DFT) levels using correlation-consistent and augmented basis sets. Double-zeta to triple-zeta complete basis set extrapolation schemes were applied to refine electronic energies, and zero-point energy corrections were included to obtain stabilization energies. Across all methods and extrapolation models, •OH addition at the C8 position of FA was consistently predicted to be the most thermodynamically favorable site, establishing the stability ordering C8 > C7 > C9. Atomic spin population analysis further supported this trend, indicating enhanced spin delocalization for the C8 adduct. These results support the thermodynamic viability of FA as a naturally derived spin-trapping agent.