Proton-Coupled Electron Transfer and Hydrogen Tunneling in Olive Oil Phenol Reactions.

ABSTRACT

Olive oil phenols are recognized as molecules with numerous positive health effects, many of which rely on their antioxidative activity, i.e., the ability to transfer hydrogen to radicals. Proton-coupled electron transfer reactions and hydrogen tunneling are ubiquitous in biological systems. Reactions of olive oil phenols, hydroxytyrosol, tyrosol, oleuropein, oleacein, oleocanthal, homovanillyl alcohol, vanillin, and a few phenolic acids with a DPPH• (2,2-diphenyl-1-picrylhydrazyl) radical in a 1,4-dioxanewater = 955 or 991 v/v solvent mixture were studied through an experimental kinetic analysis and computational chemistry calculations. The highest rate constants corresponding to the highest antioxidative activity are obtained for the ortho-diphenols hydroxytyrosol, oleuropein, and oleacein. The experimentally determined kinetic isotope effects (KIEs) for hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions are 16.0, 15.4, and 16.7, respectively. Based on these KIEs, thermodynamic activation parameters, and an intrinsic bond orbital (IBO) analysis along the IRC path calculations, we propose a proton-coupled electron transfer mechanism. The average local ionization energy and electron donor Fukui function obtained for the phenolic compounds show that the most reactive electron-donating sites are associated with π electrons above and below the aromatic ring, in support of the IBO analysis and proposed PCET reaction mechanism. Large KIEs and isotopic values of Arrhenius pre-exponential factor AH/AD determined for the hydroxytyrosol, homovanillyl alcohol, and caffeic acid reactions of 0.6, 1.3, and 0.3, respectively, reveal the involvement of hydrogen tunneling in the process.