Mechanism of scavenging action of N-acetylcysteine for the OH radical: a quantum computational study.

N-Acetylcysteine, a precursor of glutathione, is an effective antioxidant present in biological systems. The mechanism of scavenging action of N-acetylcysteine for the OH radical was studied theoretically. For this purpose, reactions of the OH radical at the different sites of N-acetylcysteine were investigated. All the relevant extrema on the potential energy surfaces were located by optimizing the geometries of the reactant and product complexes as well as those of the transition states at the BHandHLYP/AUG-cc-pVDZ level of density functional theory in the gas phase. The solvent effect of aqueous media was treated by performing single point energy calculations at the BHandHLYP/AUG-cc-pVDZ and MP2/AUG-cc-pVDZ levels of theory employing the polarizable continuum model. Correction for basis set superposition error (BSSE) was made by the counterpoise method. Rate constants for all the reaction mechanisms were calculated including the tunneling contributions. Our calculations show that the hydrogen atom of the SH group of N-acetylcysteine would be most efficiently abstracted by the OH group, which is in agreement with experimental observations.