DFT investigation of hydroxyl radical scavenging mechanisms in bioactive terpenoids from Syzygium nervosum

Reactive oxygen species, particularly the hydroxyl radical ( OH• ), drive oxidative stress and cellular damage. This study employs density functional theory (M06-2X/def2-TZVP//M06-2X/ma-def2-SVP with SMD solvation) to identify the most promising antioxidant compounds from thirteen terpenoids isolated from Syzygium nervosum . Radical adduct formation (RAF) emerges as the dominant scavenging mechanism with low kinetic barriers (14–49 kJ/mol), indicating room-temperature reactivity. Dehydroisolongifolene exhibits the lowest RAF barrier (14 kJ/mol) and exceptional multi-mechanism performance, making it the top candidate for experimental validation. (+)-Carotol shows balanced activity across multiple mechanisms, ideal for broad-spectrum applications, while (-)-myrtenol demonstrates the best RAF performance among monoterpenoids. Sesquiterpenoids outperform monoterpenoids in electron transfer due to enhanced π -conjugation, whereas monoterpenoids excel in radical addition kinetics. Oxygen functionalization, conjugation extent, and site accessibility are key determinants of antioxidant capacity. These computational predictions provide a rational basis for prioritizing dehydroisolongifolene, (+)-carotol, and (-)-myrtenol in bioassay-guided fractionation, accelerating the discovery of novel antioxidants for burn wound healing, neuroprotection, and oxidative stress management.