On the •OH and •OOH scavenging activity of 3‐methyl‐1‐pyridin‐2‐yl‐5‐pyrazolone: Comparisons with its parent compound, edaravone

Abstract

AbstractThe free radical scavenging activity of 3‐methyl‐1‐pyridin‐2‐yl‐5‐pyrazolone (pyridyl) has been studied in aqueous and lipid solutions, using the density functional theory. Four mechanisms of reaction have been considered: single electron transfer, sequential proton electron transfer (SPET), hydrogen transfer, and radical adduct formation. It was found that the reaction with •OH occur at diffusion‐limited rate, which is very similar to that of edaravone, regardless of the polarity of the environment. This indicates that they are both excellent •OH scavengers. Regarding the •OOH scavenging activity of pyridyl, in lipid media it was predicted to be about 15 times higher than that of edaravone. However, in this case they were found to be rather poor •OOH scavengers in lipid media. On the contrary, they are predicted to be excellent •OOH scavengers in aqueous solution. In fact, they were found to be among the best peroxyl radical scavengers in such medium. The rates constants of the •OOH reactions with pyridyl and edaravone, in aqueous solution, were estimated to be 1.1 × 107 and 4.3 × 108 M−1 s−1, respectively. The outstanding scavenging activity of these compounds was attributed to the presence of their anionic forms, which are much more reactive than the neutral species. The reactions with •OOH were found to take place almost exclusively by the SPET mechanism. © 2012 Wiley Periodicals, Inc.