Assessment of Free Radical Scavenging Potency of Folates. A DFT Study

Folic acid (FA) is a widely known essential compound with various biochemical properties, including antioxidant. The antiradical/antioxidant properties of FA and its physiological reduced forms: 7,8-dihydrofolate (DHF), 5,6,7,8-tetrahydrofolate (THF), 5-methyltetrahydrofolate (5-MTHF), and 5-formyltetrahydrofolate (5-FTHF) were studied using density functional theory (DFT) in gas phase and benzene, ethanol, aqueous medium. Three possible competing mechanisms for free radical inactivation are considered: hydrogen atom transfer (HAT), stepwise electron transfer-proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). Thermodynamically preferred active sites of selected folate structures have been revealed, as well as a growing order of free radical scavenging activity: FA << 5-FTHF < 5-MTHF < THF < DHF . It has been accepted that folates act as antioxidants with many free radical scavenging sites, and the hydroxyl group of the reduced forms of folic acid is the most favorable site for free radical attack.