Rusdipoetra Rahmanto Aryabraga, Suwito Hery, Tripuspaningsih Ni Nyoman, Haq Kautsar Ul
Bioinformatic Research Group, Research Centre of Bio-Molecule Engineering (BIOME), Airlangga University Jl. Ir. H. Soekarno Mulyorejo Surabaya Indonesia.
Department of Chemistry, Faculty of Science and Technology, Airlangga University Jl. Ir. H. Soekarno Mulyorejo Surabaya Indonesia
RSC Adv. 2025 Sep 17;15(41):33936-33945. doi: 10.1039/d5ra05587c.
The depolymerization of lignin is known to yield syringol and its derivatives, namely 4-allylsyringol, 4-propenylsyringol, and 4-propylsyringol, which have been demonstrated to exhibit strong antioxidant properties against HOO˙ radicals. However, the potential of these compounds as antinitrosants remains largely unexplored. Reactive nitrogen species (RNS), such as NO˙ and NOO˙ radicals, are equally as harmful as reactive oxygen species (ROS), contributing to an increased risk of diseases such as diabetes and neurodegenerative disorders. In this study, we employed a density functional theory (DFT) approach using the QM-ORSA protocol to comprehensively investigate the antinitrosant activity of these compounds in both polar and non-polar media, as well as the underlying scavenging mechanisms that influence their activity. This protocol includes thermodynamic and kinetic parameter calculations, along with comparative analyses. The results suggest that NOO˙ radical scavenging by these compounds occurs at a diffusion-limited rate, with hydrogen atom transfer (HAT) being the predominant pathway. Among the investigated compounds, 4-propenylsyringol is predicted to exhibit the highest activity, with = 1.10 × 10 M s (water) and 8.39 × 10 M s (pentyl ethanoate). Furthermore, this study highlights the role of conjugated double bonds in enhancing the antinitrosant activity of syringol derivatives. Overall, all four investigated compounds demonstrate effective NOO˙ radical scavenging capabilities across different solvent environments.
已知木质素的解聚会产生丁香酚及其衍生物，即4-烯丙基丁香酚、4-丙烯基丁香酚和4-丙基丁香酚，这些物质已被证明对HOO˙自由基具有很强的抗氧化性能。然而，这些化合物作为抗亚硝化剂的潜力在很大程度上仍未得到探索。活性氮物种（RNS），如NO˙和NOO˙自由基，与活性氧物种（ROS）一样有害，会增加患糖尿病和神经退行性疾病等疾病的风险。在本研究中，我们采用密度泛函理论（DFT）方法，使用QM-ORSA协议，全面研究这些化合物在极性和非极性介质中的抗亚硝化活性，以及影响其活性的潜在清除机制。该协议包括热力学和动力学参数计算以及比较分析。结果表明，这些化合物对NOO˙自由基的清除以扩散限制速率发生，氢原子转移（HAT）是主要途径。在所研究的化合物中，预计4-丙烯基丁香酚具有最高的活性，在水中k = 1.10×10 M s，在乙酸戊酯中k = 8.39×10 M s。此外，本研究强调了共轭双键在增强丁香酚衍生物抗亚硝化活性中的作用。总体而言，所有四种研究化合物在不同溶剂环境中均表现出有效的NOO˙自由基清除能力。
