Benchmarking the DFT methodology for assessing antioxidant-related properties: quercetin and edaravone as case studies

Abstract

The overall objective was to identify an accurate computational electronic method to virtually screen phenolic compounds through their antioxidant and free-radical scavenging activity. The impact of a key parameter of the density functional theory (DFT) approach was studied. Performances of the 21 most commonly used exchange-correlation functionals are thus detailed in the evaluation of the main energetic parameters related to the activities of two prototype antioxidants, namely quercetin and edaravone, is reported. These functionals have been chosen among those belonging to three different families of hybrid functionals, namely global, range separated, and double hybrids. Other computational parameters have also been considered, such as basis set and solvent effects. The selected parameters, namely bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) allow a mechanistic evaluation of the antioxidant activities of free radical scavengers. Our results show that all the selected functionals provide a coherent picture of these properties, predicting the same order of BDEs and PDEs. However, with respect to the reference values, the errors found at CBS-Q3 level significantly vary with the functional. Although it is difficult to evidence a global trend from the reported data, it clearly appears that LC-ωPBE, M05-2X, and M06-2X are the most suitable approaches for the considered properties, giving the lowest cumulative mean absolute errors. These methods are therefore suggested for an accurate and fast evaluation of energetic parameters related to an antioxidant activity via free radical scavenging.

Synthesis, Characterization and Antioxidant Properties of a New Lipophilic Derivative of Edaravone

“…In Table 1, the computed BDH CH and ΔE iso values for C18-EdV and EdV have been reported, showing that the two derivative exhibit very similar values, with C18-EdV probably only slightly less effective than EdV. Furthermore, these values are in line with other similar compounds [24,32,33].…”

“…The ability to donate a hydrogen atom is mainly governed by the homolytic bond dissociation enthalpy (BDH). The gas-phase BDH CH for EdV analogues, referring to the C-H bond at pyrazolone position 4, has been determined in previous theoretical studies [24,32,33], showing a good agreement with the experimental results. As a consequence, the antioxidant activity prediction of C18-EdV based upon this assumption was theoretically investigated at the DFT/B3LYP level of theory.…”

Computational strategies for predicting free radical scavengers' protection against oxidative stress: Where are we and what might follow?

“…Analyzing antioxidant protection in terms of the intrinsic reactivity of the antioxidant species is, by far, the theoretical approach most frequently found in the literature . There are several reactivity indexes that have been used for that purpose.…”

Kinetics and Mechanism of the Antioxidant Activities of C. olitorius and V. amygdalina by Spectrophotometric and DFT Methods

“…39,40 Research efforts in the use of the DFT method have revealed that the BDE and IP values are significantly influenced by levels of theory and the type of solvent, whereas basis sets do not play a significant role in BDE and IP calculations. 41 Among the DFT functionals, the B3LYP functional has been reported to show good performance in geometry optimization and its quite accurate prediction of X–H bond energetic and binding energies. 23,42 The LC-ωPBE functional has been successfully used in benchmarking the DFT method in probing antioxidant-related properties.…”

“…23,42 The LC-ωPBE functional has been successfully used in benchmarking the DFT method in probing antioxidant-related properties. 41 Although gas-phase calculations on antioxidant activities have been carried out on chlorogenic acid and luteolin-7-O-β-glucuronide, 24,38 little is still known about the calculations of the antioxidant activities of these compounds in the methanolic phase.…”