Theoretical investigation of the anti-nitrosant mechanism of syringol and its derivatives

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 <i>k</i> _overall = 1.10 × 10¹⁰ M^-1 s^-1 (water) and 8.39 × 10⁹ M^-1 s^-1 (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.