Abstract
Edaravone (EDV) is a pharmaceutical agent used for the treatment of acute strokes resulting from thrombosis or embolism in the cerebral region. Prior research demonstrated that EDV possesses the ability to safeguard brain cells, diminish atherosclerosis, shield against retinal damage, impede lipid and DNA oxidation, and restrict the production of free radicals in the liver. This work utilized DFT simulations to assess the impact of substituents on the thermodynamic properties and hydroperoxyl radical scavenging activity of EDV derivatives. The ionization energies of the EDV derivatives were shown to be significantly reduced by substituents with electron-donating property like OMe and NMe2 groups, and increased in all positions where strong electron-withdrawing substituents such as NO2 and CF3 were located. However, the bond dissociation energy (BDE) of the C4─H bond decreased by substituents at position 4. The investigation revealed that 4-NMe2-EDV is the most effective at scavenging radicals and has the potential to act as a CP450 enzyme inhibitor, particularly in lipid environments.