Mechanism of Antiradical Activity of Newly Synthesized 4,7-Dihydroxycoumarin Derivatives-Experimental and Kinetic DFT Study

Abstract

Coumarin derivatives have proven beneficial biological activities, but the mechanism of their radical scavenging potency is not fully understood. In this study, the antiradical capacity of two newly synthesized 4,7-dihydroxycoumarin derivatives: (E)-3-(1-((3-hydroxy-4-methoxyphenyl)amino)-ethylidene)-2,4-dioxochroman-7-yl acetate (A-3OH) and (E)-3-(1-((4-hydroxy-3-methoxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A-4OH) towards HO• were examined by Electron Paramagnetic Resonance (EPR) Spectroscopy and Density Functional Theory (DFT). The compounds were fully characterized by the elemental microanalysis, IR, and NMR spectroscopies. The effect of pH on the acid–base equilibria is separately discussed and the predominant species at the physiological pH were determined. Several common mechanisms (Hydrogen Atom Transfer (HAT), Single-Electron Transfer followed by Proton Transfer (SET-PT), Sequential Proton Loss followed by Electron Transfer (SPLET), Radical Adduct Formation (RAF), and Intramolecular Hydrogen Atom Abstraction (iHAA)) of radical scavenging were investigated based on thermodynamic and kinetic parameters. EPR results indicated that both compounds significantly reduce the amount of present HO•. The results of the kinetic DFT study demonstrated that both compounds predominantly exhibit antiradical capacity through HAT and SPLET mechanisms. The estimated overall rate constants (koverall) proved that A-4OH shows better antioxidant capacity than A-3OH which is well-correlated with the results obtained by EPR measurement.

Coumarin N-Acylhydrazone Derivatives: Green Synthesis and Antioxidant Potential—Experimental and Theoretical Study

“…The BDE values show a noticeably lower value in the non-polar solvent relative to the values in methanol, as shown in Table 5. These results are expected and in good agreement with the results of earlier research [26,[36][37][38][39][49][50][51][52][53].…”

“…For the assessment of the antioxidant activity, three main radical scavenging mechanisms-Hydrogen Atom Transfer (HAT), Single-Electron Transfer Followed by Proton Transfer (SET-PT), and Sequential Proton Loss-Electron Transfer (SPLET) were used [37][38][39][40]. In the first reaction mechanism, the O-H bond is homolytic cleavage, resulting in the separation of a hydrogen atom and a radical species (A-O • ) (Equation ( 1)).…”

Degradation Mechanisms of 4,7-Dihydroxycoumarin Derivatives in Advanced Oxidation Processes: Experimental and Kinetic DFT Study

“…The M06-2X/6-311++G(d,p) theoretical model (with polarization and diffuse functions included) was employed for the optimization of the structures of the coumarin derivatives, as suggested in [29]. The applied theoretical model is suitable for thermodynamic and kinetic analyses of various reactions [23][24][25]30,31]. The conductorlike polarizable continuum model (CPCM, water (ε = 78.36)) was applied to approximate the solvent effect in the experimental environment [32].…”

“…A similar methodology has been successfull plied to other coumarin derivatives [23,24]. The applied methodology was based on the calculation of the thermodynamic kinetic parameters of generally accepted radical scavenging mechanisms, such a drogen atom transfer (HAT), single-electron transfer followed by proton tra (SE−TPT), sequential proton loss followed by electron transfer (SPLET), and radica duct formation (RAF) [25,26]. In addition, assessment of the reactivity of the n formed radical species utilizing appropriate models for biomolecular targets was o Structures of previously synthesized [21] aminophenol derivatives of 4,7−dihydroxycoumarin.…”

Density functional theory investigation of mechanisms of degradation reactions of sulfonated PEEK membranes with OH radicals in fuel cells: addition–elimination reactions and acid catalyzed water elimination

“…It has been shown to provide good performance in calculating bond dissociation energies for reactions involving radicals [25]. It has very recently been implemented to calculate the reaction pathways, including transition states, of reactions of OOH and OH radicals in aqueous solution [26][27][28] Within reference 6, additional calculations of the enthalpies of a number gas-phase reactions involving radicals also illustrated that M062X/6-311 + G(3df,2p) singlepoint calculations following M062X/6-311 + G(2d,2p) optimizations can very accurately reproduce the energetics of a number of reactions involving breaking of C-O and C-C bonds to form H radicals as well as radicals of carbon and oxygen atoms such as CH 3 , OCH 3 and OH radicals.…”