A DFT analysis of the antioxidant capacity of scopolin and scopoletin

Scopolin and scopoletin belong to the class of coumarins and have experimentally proven natural antioxidants. Natural antioxidants are crucial in mitigating the impact of oxidants in the human body through radical scavenging. Even though scopolin and scopoletin are proven antioxidants by experimental results, their antioxidant mechanisms still remained unexplained. In this study, Density functional theory (DFT) calculations were used to study the radical scavenging mechanisms of both scopolin and scopoletin using kinetic and thermodynamics parameters. The global parameters indicated that both scopolin and scopoletin have antioxidant properties. The band gap energy $\left({\Delta E}_{\text{HOMO}-\text{LUMO}}\right)$ revealed that scopoletin (4.18 eV) has strong antioxidant activity compared to scopolin (4.31 eV). These studies found that hydrogen atom transfer (HAT) is the primary mechanism for CH₃OO• radical scavenging at the C-H bond in scopolin (91.98 kcal.mol^-1) and the O-H bond in scopoletin (77.05 kcal.mol^-1) due to their lowest bond dissociation energies. The calculated activation energy ( $E_a$ ) for the radical scavenging reaction, reconfirmed scopoletin ( $E_a$ =11.19 kcal.mol^-1) performed as a better antioxidant compared to scopolin ( $E_a$ =20.91 kcal.mol^-1). In this study, the results of DFT calculations confirmed that scopoletin exhibits a higher antioxidant capacity, and HAT mechanism is the most effective radical scavenging mechanism.

The antioxidant activity of scopolin and scopoletin was determined by DFT at the B3LYP/6-31G(d) level of theory. Global parameter calculations and frontier molecular orbital analysis were conducted to assess these compounds' capacity for scavenging radicals. Hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SETPT), and sequential proton loss electron transfer (SPLET) mechanisms were the three main mechanisms that were taken into consideration. The potential energy surface (PES) verified the most appropriate processes shown by the enthalpy calculations.