Density Functional Study of the Radical Reactions of 3-Methyl-1-phenyl-2-pyrazolin-5-one (MCI-186): Implication for the Biological Function of MCI-186 as a Highly Potent Antioxidative Radical Scavenger

Abstract

The radical reaction intermediates and products from the antioxidative radical scavenger MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one (1), and its model system 1,3-dimethyl-2-pyrazolin-5-one (2) are investigated by a density functional method (B3LYP/6-31G*) with the self-consistent isodensity polarized continuum model (SCI-PCM). It is shown that a radical intermediate, denoted 4, is produced as a result of one-electron oxidation of 2 by active oxygen species. The subsequent reactions are studied along the scheme proposed previously by an in vitro experimental study of 1. For 4, the isotropic hyperfine coupling constants are calculated using the B3LYP/EPR-II basis set, and the results are compared with the literature values given by ESR measurements at room and body temperatures. Consequently, it is confirmed that the calculation reproduces well the experimental results. One of the most important findings is that the radical intermediate is stabilized by delocalization of spin population over the pyrazolin...