In Silico design of hydroxylated coumarins and thermodynamic investigation of their free radical scavenging mechanism

Coumarin and its derivatives have been found to exhibit antioxidant activities. However, a detailed description of the thermodynamics of free radical scavenge by these compounds has not received adequate attention. In order to explore the reaction energetics of the free radical scavenging mechanism of newly designed coumarin compounds, a theoretical study, based on density functional theory (DFT) using the Becke’s three-parameter Lee-Yang-Parr hybrid functional (B3LYP) in connection with the 6-311G* basis set, was employed. Hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) mechanisms were investigated by thermodynamic studies in the gas phase and aqueous solution. Various reaction enthalpies such as bond dissociation enthalpy (BDE), adiabatic ionization potential (AIP), proton dissociation enthalpy (PDE), proton affinity (PA), electron transfer enthalpy (ETE) and Gibbs free energy changes that characterize these mechanisms were calculated. The high solvation enthalpies of the electron and proton resulted in lower values of AIP and PA respectively in aqueous solution than in the gas phase. The reaction Gibbs free energy results indicate that hydroxylated coumarin molecules are efficient free radical scavengers by HAT and SPLET mechanisms in the gas phase and aqueous solution. The SET-PT mechanism was thermodynamically prohibited in the gas phase, but feasible in aqueous solution. Also these compounds were observed to be more reactive towards HOO. than CH₃OO. radicals.