Vlocskó R Bernadett, Mastyugin Maxim, Török Béla, Török Marianna
Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA, 02125, USA.
Sci Rep. 2025 Jan 2;15(1):73. doi: 10.1038/s41598-024-83982-4.
Oxidative stress, associated with excessive production of reactive oxygen and nitrogen species (ROS, RNS), contributes to the development and progression of many ailments, such as aging, cardiovascular diseases, Alzheimer's disease, Parkinson's disease, diabetes, cancer, preeclampsia or multiple sclerosis. While phenols and polyphenols are the most studied antioxidants structurally similar compounds such as anilines or thiophenols are sporadically analyzed despite their radical scavenging potential. This work assesses the impact of structural features of phenols and thiophenols on their antioxidant activity. Seventeen pairs of phenol/thiophenol analogues, possessing both electron-donating and withdrawing groups were selected for this study. Several physicochemical properties of the compounds were determined by density functional theory (DFT) calculations at the (U)B3LYP/6-311++G(d,p) level of theory for gas phase calculations and at the (U)B3LYP/6-311++G(d,p) scrf = (smd, solvent = water) level for the solvated ones. Correlations between calculated properties and experimental radical scavenging activities were investigated to identify the pivotal physical characteristics contributing to antioxidant efficiency. These include S-H and O-H bond distances and bond dissociation enthalpies (BDE), dipole moments, logP values, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbital energies, and the HOMO-LUMO gap energies that were calculated at the M06-2X/6-311++G(d,p) level of theory, and Fukui functions. The experimental activity was evaluated using the 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1picrylhydrazyl (DPPH) radical scavenging assays. Several compounds exhibited superior scavenging abilities, surpassing that of the reference antioxidant Trolox. The extensive DFT calculations revealed that in the gas phase, lower BDE values, compared to IP and PA, suggested that the HAT mechanism predominates in case of these compound groups. In contrast, in water, significant reductions in PA due to solvent effects suggested that the SPLET mechanism is dominant under aqueous conditions.
氧化应激与活性氧和氮物种（ROS、RNS）的过量产生相关，它会促使许多疾病的发生和发展，如衰老、心血管疾病、阿尔茨海默病、帕金森病、糖尿病、癌症、先兆子痫或多发性硬化症。虽然酚类和多酚类是研究最多的抗氧化剂，但结构类似的化合物，如苯胺或硫酚，尽管具有自由基清除潜力，但却很少被分析。这项工作评估了酚类和硫酚类的结构特征对其抗氧化活性的影响。本研究选择了17对同时具有供电子基团和吸电子基团的酚/硫酚类似物。通过密度泛函理论（DFT）计算确定了化合物的几种物理化学性质，气相计算在（U）B3LYP/6-311++G（d，p）理论水平下进行，溶剂化化合物在（U）B3LYP/6-311++G（d，p）scrf =（smd，溶剂 = 水）水平下进行。研究了计算性质与实验自由基清除活性之间的相关性，以确定对抗氧化效率有重要贡献的关键物理特性。这些特性包括S-H和O-H键距离、键解离焓（BDE）、偶极矩、logP值、最高占据分子轨道（HOMO）和最低未占据分子轨道（LUMO）的轨道能量，以及在M06-2X/6-311++G（d，p）理论水平下计算的HOMO-LUMO能隙能量和福井函数。使用2,2'-联氮-双-（3-乙基苯并噻唑啉-6-磺酸）（ABTS）和2,2-二苯基-1-苦基肼（DPPH）自由基清除试验评估了实验活性。几种化合物表现出优异的清除能力，超过了参考抗氧化剂Trolox。广泛的DFT计算表明，在气相中，与电离势（IP）和质子亲和势（PA）相比，较低的BDE值表明这些化合物组的氢原子转移（HAT）机制占主导。相反，在水中，由于溶剂效应导致PA显著降低，表明在水相条件下，单电子转移（SPLET）机制占主导。
