Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.
Faculty of Chemical Engineering and Technology, University of Zagreb, 10000 Zagreb, Croatia.
Int J Mol Sci. 2024 Jun 7;25(12):6341. doi: 10.3390/ijms25126341.
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-dioxane:water = 95:5 or 99:1 / 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 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 / 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.
橄榄油酚被认为是具有许多积极健康影响的分子，其中许多依赖于其抗氧化活性，即向自由基转移氢的能力。质子偶联电子转移反应和氢隧穿在生物系统中普遍存在。在 1,4-二恶烷：水=95:5 或 99:1/溶剂混合物中，研究了橄榄油酚、羟基酪醇、酪醇、橄榄苦苷、橄榄苦苷、橄榄苦苷、香草醇、香草醛和几种酚酸与 DPPH•（2,2-二苯基-1-苦基肼基）自由基的反应通过实验动力学分析和计算化学计算。对于邻二酚羟基酪醇、橄榄苦苷和橄榄苦苷，获得了对应于最高抗氧化活性的最高速率常数。羟基酪醇、香草醇和咖啡酸反应的实验测定动力学同位素效应（KIE）分别为 16.0、15.4 和 16.7。基于这些 KIE、热力学活化参数以及 IRC 路径计算中的固有键轨道（IBO）分析，我们提出了质子偶联电子转移机制。酚类化合物的平均局部电离能和电子给体 Fukui 函数表明，最具反应性的供电子位点与芳香环上方和下方的π电子相关，支持 IBO 分析和提出的 PCET 反应机制。羟基酪醇、香草醇和咖啡酸反应的 KIE 和 Arrhenius 前指数因子/的同位素值较大，分别为 0.6、1.3 和 0.3，表明氢隧穿在该过程中起作用。
