Sarcouncil Journal of Biomedical Sciences

Abstract: Reactive oxygen species (ROS) play dual roles in cellular physiology, contributing to both essential signaling and oxidative damage in pathological and environmental contexts. Melatonin and its derivatives have emerged as potent multi-mechanism antioxidants, exhibiting neuroprotective, anti-inflammatory, and detoxifying properties. This systematic review, conducted in accordance with PRISMA 2020 guidelines, synthesizes computational evidence on radical scavenging and spin trapping mechanisms involving melatonin derivatives. Data were collated from PubMed, Scopus, Web of Science, EMBASE, and ScienceDirect, focusing on studies employing quantum chemical methods, including DFT and QM/MM simulations. Key findings reveal that melatonin derivatives predominantly neutralize ROS via hydrogen atom transfer (HAT), with contributions from single electron transfer (SET) and radical adduct formation (RAF) pathways. Computational spin trapping simulations using agents like DMPO confirm the thermodynamic feasibility of adduct formation, supported by hyperfine coupling constant predictions. Structural features such as methoxy and amide groups significantly enhance radical stabilization. Despite methodological heterogeneity, and in silico models demonstrate strong predictive power for antioxidant performance. Translating these insights into biomedical and environmental interventions requires standardized computational protocols, kinetic integration, and experimental validation.