Kowalska-Baron Agnieszka
Institute of Natural Products and Cosmetics, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland.
Int J Mol Sci. 2024 Nov 27;25(23):12753. doi: 10.3390/ijms252312753.
In this study, the DFT/M062X/PCM method was applied to investigate thermodynamic and kinetic aspects of reactions involved in possible mechanisms of antioxidant activity of caffeic acid against HOO radicals in aqueous medium at different pH values. Kinetic parameters of the reactions involved in HAT (Hydrogen Atom Transfer), RAF (Radical Adduct Formation), and SET (Single Electron Transfer) mechanisms, including reaction energy barriers and bimolecular rate constants, were determined, and identification and characterization of stationary points along the reaction pathways within HAT and RAF mechanisms were performed. Inspection of geometrical parameters and spin densities of the radical products formed within HAT and RAF mechanisms revealed that they are stabilized by hydrogen bonding interactions and the odd electron originated through the reaction with the HOO radical is spread over the entire molecule, resulting in significant radical stabilization. Thermodynamic and kinetic data collected in this study indicated that increasing pH of the medium boosts the antioxidant activity of caffeic acid by reducing the energy required to generate radicals within the RAF and/or HAT mechanism and, at extremely high pH, where the trianionic form of caffeic acid is a dominant species, by the occurrence of an additional fast, diffusion-limited electron-related channel.
在本研究中，采用密度泛函理论（DFT）/M062X/极化连续介质模型（PCM）方法，研究了在不同pH值的水介质中，咖啡酸对HOO自由基抗氧化活性可能机制中涉及的反应的热力学和动力学方面。确定了氢原子转移（HAT）、自由基加合物形成（RAF）和单电子转移（SET）机制中涉及的反应的动力学参数，包括反应能垒和双分子速率常数，并对HAT和RAF机制中反应途径上的驻点进行了识别和表征。对HAT和RAF机制中形成的自由基产物的几何参数和自旋密度的检查表明，它们通过氢键相互作用得以稳定，并且通过与HOO自由基反应产生的单电子分布在整个分子上，从而导致显著的自由基稳定化。本研究收集的热力学和动力学数据表明，提高介质的pH值可通过降低RAF和/或HAT机制中产生自由基所需的能量来增强咖啡酸的抗氧化活性，并且在极高pH值下，当咖啡酸的三阴离子形式占主导时，通过出现一个额外的快速、扩散受限的电子相关通道来增强其抗氧化活性。
