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

Abstract

The 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.

A DFT analysis on the radical scavenging activity of oxygenated terpenoids present in the extract of the buds of Cleistocalyx operculatus

“…This is coherent with the results reported in previous studies. 19,26,36,37 Among studied compounds, falcarinol seems to be the most efficient antioxidant molecule via both HAT and SPLET mechanisms. And a-vetivone is also a promising antioxidant compound.…”

A Computer-Assisted Systematic Search for Melatonin Derivatives with High Potential as Antioxidants

“…M05-2X is a global hybrid exchangecorrelation GGA functional designed for thermochemistry, kinetics and noncovalent interactions (96), it has also been recommended for calculating reaction energies involving free radicals (98). Furthermore, the M05-2X functional has been widely used for estimating the pKa values, the bonding dissociation energies and, in general, the free radical scavenging activity of several antioxidant molecules (99)(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111). SMD is considered a universal solvation model, due to its applicability to any charged or uncharged solute in any solvent or liquid medium for which a few key descriptors are known (97).…”

On the hydroperoxyl radical scavenging activity of two Edaravone derivatives: mechanism and kinetics

“…This particular derivative (D1) was found to be among the best peroxyl scavengers known so far, with an efficiency similar to that its parent molecule, EDA (8.8 Â 10 7 M À1 s À1 ), [92] sesamol (2.4 Â 10 8 M À1 s À1 ), [99] and caffeic acid (2.7 Â 10 8 M À1 s À1 ).…”

“…) [92] 9.1 times faster than C1, but 2.6 times slower than D1. However, they all react very fast with peroxyl radicals under such conditions.…”

“…Under such conditions, they were found to react about 78 and 106 times faster than EDA (0.12 M À1 s À1 ), [92] which suggests that further investigations aiming to increase the peroxyl scavenging activity of this kind of compounds in lipid media, via structural modifications, are worthwhile. On the other hand, in aqueous solution at physiological pH, EDA reacts with…”