Use and Abuse of the DPPH(•) Radical Foti, Mario C
Journal of agricultural and food chemistry,
2015-Oct-14, Volume:
63, Issue:
40
Journal Article
Peer reviewed
The 2,2-diphenyl-1-picrylhydrazyl (DPPH(•)) radical is approaching 100 years from its discovery in 1922 by Goldschmidt and Renn. This radical is colored and remarkably stable, two properties that ...have made it one of the most popular radicals in a wide range of studies. First, there is the evaluation of the antioxidant abilities of phenols and other natural compounds (A-H) through a "test" that-at a closer look-is utterly inappropriate. In fact, the test-derived EC50, that is, the concentration of A-H able to scavenge 50% of the initial DPPH(•), is not a kinetic parameter and hence its purported correlation with the antioxidant properties of chemicals is not justified. Kinetic measurements, such as the second-order rate constants for H-atom abstraction from A-H by DPPH(•), in apolar media, are the only useful parameters to predict the antioxidant ability of A-H. Other applications of DPPH(•) include kinetic and mechanistic studies, kinetic solvent effects, EPR spectroscopy, polymer chemistry, and many more. In this review these applications are evaluated in detail by showing the usefulness of some and the uselessness of others. The chemistry of DPPH(•) is also briefly reviewed.
•Antioxidant potential of one natural and three synthetic additives have been compared.•In general, O-H bonds are weaker than C-H in all species.•BHT is the best radical scavenger within the studied ...set of species.•The ranking of the species is the following: BHT > BHA ≈ TBHQ > curcumin A > curcumin D.
The antioxidant potential of commonly used synthetic and natural antioxidant additives, including butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), tert‑butylhydroquinone (TBHQ), and natural additive, curcumin have been studied and compared by calculating the bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA), and electron transfer enthalpy (ETE) values for each potential hydrogen donor site. The results indicate that, in each additive an OH group has the highest antioxidant potential (lowest BDE value). The studied molecules can be ranked based on their antioxidant potential as follows: BHT > BHA ≈ TBHQ > curcumin A > curcumin D. By comparing with commonly used polymers, in each studied species, there is at least one X-H bond which has a lower BDE value than in the corresponding polymeric material. Thus, all studied additives are potentially applicable to protect polymeric materials. BHT is the best radical scavenger additive in case of the hydrogen atom transfer (HAT), and the sequential proton loss electron transfer (SPLET) mechanisms to donate a H atom, but in single electron transfer proton transfer (SETPT) curcumin could also be suitable.
Moracin T is a natural product isolated from Morus mesozygia (Moraceae), which acts as potent antioxidant agent. In this study, density functional theory-based computational methods have been ...performed to evaluate systematically the radical scavenging behaviour of this compound. Structural characteristics such as frontier molecular orbitals and molecular electrostatic potential mapping have been investigated. Thermodynamic parameters related to the three main antiradical mechanisms, hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SETPT), and sequential proton loss electron transfer (SPLET) have been studied. In addition, two variants of SPLET mechanism namely sequential proton loss hydrogen atom transfer (SPLHAT) and double sequential proton loss electron transfer (D-SPLET) have been investigated. The reaction of moracin T with hydroperoxyl radical (HOO
*
), as representative reactive oxygen species, was also studied. The obtained results are of great significance in better understanding the chemical mechanism of the radical-scavenging action and open new perspectives for the design of new potent antioxidant agents.
The present paper describes combined experimental and theoretical studies of twelve heterocyclic compounds bearing hydrazone functional group (1–12). Experimentally, the free radical scavenging ...activity of all the compounds have been investigated using DPPH, ABTS, and DMSO alkaline assays. The obtained results showed that these compounds are potent antiradical agents. The best results have been obtained with the imidazole derivatives 5 and 12, which showed higher antiradical activity than the BHT standard in DPPH and ABTS assays. Theoretical calculations, by means of DFT/B3LYP approach, were carried out in order to explain the experimental results. Some structural characteristics such as molecular descriptors, highest occupied molecular orbital, and molecular electrostatic potential mapping have been computed. The mechanisms, HAT (hydrogen atom transfer), SETPT (sequential electron transfer proton transfer), and SPLET (sequential proton loss electron transfer) have been studied and discussed. In addition, the reactions toward HO•, MeO•, HOO•, and MeOO• radicals have been investigated. As results, the radical scavenger properties of the studied compounds were confirmed. The HAT was found to be the thermodynamically dominant mechanism in the gas-phase for all the studied compounds, whereas the SPLET mechanism is the thermodynamically favorable pathway in ethanol. A good correlation with DPPH and ABTS assays was found between experimental and theoretical results.
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•The antiradical activity of twelve heterocyclic hydrazone compounds has been studied.•DPPH, ABTS, and DMSO alkaline assays were employed to investigate the in vitro antiradical activity.•DFT calculations of the antiradical mechanisms have been performed.•The reactions with typical reactive oxygen species have been investigated.
Since the last few years, the growing interest in the use of natural and synthetic antioxidants as functional food ingredients and dietary supplements, is observed. The imbalance between the number ...of antioxidants and free radicals is the cause of oxidative damages of proteins, lipids, and DNA. The aim of the study was the review of recent developments in antioxidants. One of the crucial issues in food technology, medicine, and biotechnology is the excess free radicals reduction to obtain healthy food. The major problem is receiving more effective antioxidants. The study aimed to analyze the properties of efficient antioxidants and a better understanding of the molecular mechanism of antioxidant processes. Our researches and sparing literature data prove that the ligand antioxidant properties complexed by selected metals may significantly affect the free radical neutralization. According to our preliminary observation, this efficiency is improved mainly by the metals of high ion potential, e.g., Fe(III), Cr(III), Ln(III), Y(III). The complexes of delocalized electronic charge are better antioxidants. Experimental literature results of antioxidant assays, such as diphenylpicrylhydrazyl (DPPH) and ferric reducing activity power assay (FRAP), were compared to thermodynamic parameters obtained with computational methods. The mechanisms of free radicals creation were described based on the experimental literature data. Changes in HOMO energy distribution in phenolic acids with an increasing number of hydroxyl groups were observed. The antioxidant properties of flavonoids are strongly dependent on the hydroxyl group position and the catechol moiety. The number of methoxy groups in the phenolic acid molecules influences antioxidant activity. The use of synchrotron techniques in the antioxidants electronic structure analysis was proposed.
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•The radical scavenging study of BOH towards HO• was investigated by the DFT method.•The SOMO showed that the PCET is dominant mechanism for H atom abstraction.•Six positions in BOH ...structure were active for radical adduct formation with HO•.•The kinetically preferred pathway for the anionic species is electron transfer.•Molecular docking confirmed inhibitory effectiveness of BO− to the GLOI receptor.
Baicalein (BOH) is an essential flavone molecule with proven significant scavenging activity towards various reactive species, although the actual mechanism has not been fully elucidated. Three common mechanisms: Hydrogen Atom Abstraction (HAA), Radical Adduct Formation (RAF), and Electron Transfer (EA), for the reaction between BOH and HO• have been investigated thermodynamically and kinetically in water and penthylethanoate. Based on the pKa values of BOH, the percentages of various acid-base species were estimated and subsequently incorporated into the described procedures. Changes in Gibbs free energy of HAA reactions demonstrated the spontaneity of hydrogen transfer from each OH group of BOH with reaction rates of 1.8 × 107 and 7.5 × 104 M−1 s−1. This process occurred through Proton Coupled-Electron Transfer (PCET) mechanism. Reactions involving RAF processes were operable in six places, with rate constants ranging from 4.8 × 104 to 3.0 × 108 M−1 s−1. Reaction rates calculated for electron transfer from anionic species (BO-) were the kinetically most favorable reaction pathway of the order of 109 M−1 s−1, which unequivocally shows that these reactions are diffusion controlled. These results shed new light on BOH chemistry and its possible medical use. The molecular docking analysis was performed to identify the inhibition potency of the baicalein-anion against Glyoxalase I (GLOI) receptor. This study demonstrated that molecular docking analysis is an important tool for evaluating the interactions of biologically significant compounds, particularly their many acid-base forms.
This paper describes a theoretical comparative study of the antiradical properties of six aromatic compounds namely eugenol (EUG), safrole (SAF), myristicin (MYR), carvacrol (CAR), cinnamaldehyde ...(CIN), and isoeugenol (ISO) found in antioxidant essential oils. Using density functional theory (DFT) calculations, some structural characteristics such as molecular descriptors, frontier molecular orbitals, and molecular electrostatic potential have been studied. Three main antiradical mechanisms, hydrogen atom transfer (HAT), single electron transfer proton transfer (SETPT, and sequential proton loss electron transfer (SPLET) have been also investigated. In addition, the Gibbs free energies related to the reactions of the studied compounds with two reactive oxidant species (HO
*
and HOO
*
) have been computed. Throughout the study, the implicitly of polar and nonpolar solvents (water and benzene) has been taken into account. It was found that EUG, SAF, CIN, and ISO scavenge free radicals by means of a CH bond, while CAR and ISO by means of an OH bond. In the gas and benzene phases, all the studied compounds prefer to undergo HAT mechanism, while in water, SPLET is more favoured for CIN, CAR, and ISO and both HAT and SPLET are possible for EUG, SAF, and MYR. In all the studied mediums, the sequence of the antiradical potential is: MYR ≈ SAF ≈ ISO ≈ EUG > CAR > CIN. This order is in line with the available experimental results.
DFT-based computational calculations have been used to investigate the hydroperoxyl radical scavenging activity of four essential oil constituents namely thymol (Thy), rosefuran (Ros), terpinolene ...(Ter), and umbelliferone (Umb). Different reaction mechanisms including formal hydrogen transfer (FHT), radical adduct formation (RAF), sequential proton loss electron transfer (SPLET), and sequential electron transfer proton transfer (SETPT) have been examined in the gas phase and physiological environments. It was found that the HOO radical scavenging activity of these compounds is strongly influenced by the environment, which becomes more important in water than pentyl ethanoate. According to the overall reaction rate constants, the phenolic compounds Thy and Umb are predicted to exhibit excellent activity in aqueous solution. Umb with an overall rate constant of 1.44 × 108M−1s−1 at physiological pH is among the best HOO radical scavengers in water with activity comparable to that of caffeic acid, higher than those of ascorbic acid, guaiacol and eugenol, and much higher than that of Trolox.
The hydroperoxyl radical scavenging activity and mechanism of four essential oil components were revealed using thermodynamic and kinetic calculations. Display omitted
•HOO scavenging activity of four essential oil constituents has been investigated.•All of the studied compounds are moderate HOO scavengers in lipid medium.•Rosefuran and terpinolene are good HOO scavengers in water.•Thymol and umbelliferone are excellent HOO scavengers in water.•Via the SPLET mechanism, umbelliferone is among the best HOO scavengers in water.
In this communication we draw attention on serious flaws that plague recently reported antioxidant properties of atorvastatin (ATV) in methanol. First and foremost, we emphasize that the O-H bond ...dissociation energies (BDE) of about 400kcal/mol previously reported are completely wrong. Further, we present results refuting the previous claim that the proton affinity (PA) of ATV is smaller than that of the ascorbic acid. That unfounded claim relies on incorrect data for PA’s ascorbic acid (which we correct here) circulated in the literature. Further, we correct the values of the chemical reactivity indices (e.g., chemical hardness, electrophilicity index, electroaccepting and electrodonating powers), which were inadequately estimated previously via Kohn–Sham HOMO and LUMO energies. Finally, our updated values for O-H bond dissociation enthalpy (BDE = 91.4kcal/mol) and electron transfer enthalpy (ETE = 105.7kcal/mol) tentatively suggest that direct H-atom transfer (HAT) and sequential proton loss electron transfer (SPLET) may coexist.
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•Atorvastatin does not have the unrealistically strong O-H bonds estimated recently.•Atorvastatin does not have proton acidity lower than ascorbic acid.•Proton affinity of ascorbic acid drastically overestimated previously is adequately computed.•Global molecular descriptors realistically calculated without using questionable Kohn–Sham orbitals.
The antioxidant properties of echinatin (Ech), isolated from liquorice, have recently been reported. It is well known that the free radical species can be deactivated by phenolic antioxidants via ...different mechanistic pathways. In this work, the scavenging of eighteen different reactive oxygen species (ROS) has been considered, focussing on three main working mechanisms, namely hydrogen atom transfer (HAT), single electron transfer followed by proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET). The investigations have been performed in different dielectric media, viz. gas phase, benzene, methanol and aqueous solution, using density functional theory (DFT) calculations at the M05-2X/6-311++G** level. Various molecular descriptors have been elucidated for Ech as well as the ROS and compared with the reference antioxidant molecule, trolox. In addition, the redox potentials and the equilibrium constants have been calculated to discuss the feasibility of the overall scavenging process. The results demonstrate that the 4-OH group is the first site for H-atom donation, followed by 4'-OH. Further, it has been found that HAT would be the most favourable mechanism in the gas phase. The SPLET mechanism is thermodynamically favoured in polar media like water and methanol, while in the case of non-polar solvents like benzene, the two mechanisms are observed to be competitive.
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