OH Radical Scavenging Activity of Edaravone: Mechanism and Kinetics

Abstract

The reactions of OH radicals with the neutral and anionic forms of Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, EDA) have been studied using Density Functional Theory. Different mechanisms and reaction sites have been considered. The overall rate constant was found to be diffusion-limited (1.35 × 10(10) M(-1) s(-1), in aqueous solution), and in excellent agreement with the experimental results. Therefore, the present work supports previous evidence that EDA is an excellent (•)OH scavenger. The anionic form of EDA is predicted to react 8.6 times faster than its neutral form. The preponderant mechanism was found to be different depending on the form of EDA reacting with the radical. For the anionic form, the single electron transfer mechanism was found to be the one contributing the most to the overall reactivity toward (•)OH (∼ 44%), closely followed by radical adduct formation (∼40%). For the neutral form, the latter was found to be the main mechanism, with contributions larger than 98%, regardless of the polarity of the environment. For the global reactivity of EDA toward OH radicals, at physiological pH, the main mechanism of reaction is proposed to be the sequential electron proton transfer. A detailed analysis of the UV-vis spectra is also provided. The excellent agreement with the available experimental data supports the reliability of the new information provided in the present work.

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

“…The derivative referred to as C1 in this work (3-(4-(3-methyl-5-oxo-4,5-dihydro-1-pyrazol-1-yl) phenoxy) propyl nitrate; Scheme 1) was found to be among the best ones. This is in agreement with previous results from our group based on the electron-donating capability and ease of deprotonation for a large set of EDA derivatives, [44] as well as on the kinetic of their single electron transfer (SET) reactions with free radicals of different nature in aqueous solution. [45] In both works, C1 was found to be one of the best possible free radical scavengers among the studied EDA derivatives.…”

“…[34,84] The prevailing one among them is the keto form, with a population~97%. [85] Therefore, it Scheme 1. EDA derivatives, C1 and D1…”

“…According to the results from those previous works, [44,45] there is another EDA derivative, here referred to as D1 (1-(4-aminophenyl)-3-methyl-1-pyrazol-5-one, Scheme 1), that is also among those with highest free radical scavenging activity via SET. However, in those works, the free radical scavenging activity of these compounds through hydrogen transfer (HT) or radical adduct formation (RAF) mechanisms were not investigated; and to our best knowledge, there is no information available on the possible role of such mechanisms on the free radical scavenging activity of EDA derivatives.…”

Computational consideration on advanced oxidation degradation of phenolic preservative, methylparaben, in water: mechanisms, kinetics, and toxicity assessments

“…At this point, the computational results are expected to interpret the experimental findings and provide theoretical support for the conclusions of the experimental MPB degradation results. In addition, as a approach of cost-effective, convenient, and avoiding the use of animals for toxicological study [22,23], computational approach is frequently adopted to investigate the molecular basis of environmental, chemical, and biological processes [24,25]. To date, no computational study has been reported on the mechanisms and kinetics of MPB degradation using AOPs, as well as the toxicity assessment of its degradation products.…”

Reactivity Trends in Radical-Molecule Tropospheric Reactions - A Quantum Chemistry and Computational Kinetics Approach

“…More recently in the Truhlar group (University of Minnesota) new DFT methods have been developed that can achieve the required accuracy for kinetic and thermodynamic calculations without the need of refining energies with post Hartree-Fock methods. This is the case of the M05-2X functional that we have adopted for some of our recent studies (Zavala-Oseguera et al, 2009;Galano et al 2011Pérez-González & Galano 2011;Leon-Carmona & Galano, 2011;Galano 2011;Gao et al, 2010;.…”