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

Reactive oxygen species, particularly the hydroxyl radical ([Formula: see text]), 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.