Modeling the activity of glutathione as a hydroxyl radical scavenger considering its neutral non-zwitterionic form.

Glutathione is an immensely important antioxidant, particularly in the central nervous system. The scavenging mechanism of glutathione towards the OH radical was studied theoretically, considering its neutral, non-zwitterionic form relevant to acidic media. Gibbs free barrier and released energies involved in hydrogen abstraction from the different sites of glutathione by an OH radical were studied at the B3LYP/6-31G(d,p), B3LYP/AUG-cc-pVDZ, M06/AUG-cc-pVDZ, M06-2X/AUG-cc-pVDZ levels of density functional theory. Solvation in bulk aqueous media was also studied at all these levels of theory employing the polarizable continuum model. Our study shows that a hydroxyl radical can abstract a hydrogen atom easily from glutathione. Thus, glutathione is shown to be an efficient scavenger of OH radicals, which is in agreement with the results of previous studies.