Single Electron Transfer-proton Transfer Research Articles

Flavonoid Oxidation Potentials and Antioxidant Activities-Theoretical Models Based on Oxidation Mechanisms and Related Changes in Electronic Structure.

Herein, I will review our efforts to develop a comprehensive and robust model for the estimation of the first oxidation potential, Ep1, and antioxidant activity, AA, of flavonoids that would, besides enabling fast and cheap prediction of Ep1 and AA for a flavonoid of interest, help us explain the relationship between Ep1, AA and electronic structure. The model development went forward with enlarging the set of flavonoids and, that way, we had to learn how to deal with the structural peculiarities of some of the 35 flavonoids from the final calibration set, for which the Ep1 measurements were all made in our laboratory. The developed models were simple quadratic models based either on atomic spin densities or differences in the atomic charges of the species involved in any of the three main oxidation mechanisms. The best model takes into account all three mechanisms of oxidation, single electron transfer-proton transfer (SET-PT), sequential proton loss electron transfer (SPLET) and hydrogen atom transfer (HAT), yielding excellent statistics (R2 = 0.970, S.E. = 0.043).

Comprehensive density functional theory studies on Kojic acid derivatives: NBO, basicity, aromaticity and antioxidant investigations

The 4-pyrone scaffold inherent in Kojic acid demonstrates substantive biological attributes. This present inquiry delves into the structural and electronic characteristics of twelve Kojic acid derivatives employing the DFT/B3LYP 6–311++G(d, p) methodology, scrutinizing their behavior in the gas phase and water. Aromaticity indices reveal the aromatic nature of the six-membered rings within the conjugated acids of these compounds. Notably, compound 10, housing an imine group, exhibits heightened basicity surpassing that of 1,8-bis(dimethylamino)naphthalene, potentially categorizing it as a superbase. The assessment of antioxidant activity encompasses both hydrogen atom transfer and single electron transfer-proton transfer mechanisms, revealing a discernible impact of X and Y heteroatoms on the antioxidant activity of structures 1–12.

Predicting the activity of methoxyphenol derivatives antioxidants: II-Importance of the nature of the solvent on the mechanism, a DFT study.

The various mechanisms of primary antioxidant action of a series of 2-Methoxyphenols are investigated in the present work. The electronic properties have just been studied in a joint article, so that we focus here on Hydrogen Atom Transfer (HAT), Single Electron Transfer-Proton Transfer (SET-PT) and Sequential Proton-Loss Electron-Transfer (SPLET) mechanisms. The two computational approaches used in the previous study of the structure and reactivity of these compounds [Computational and Theoretical Chemistry 1229 (2023) 114287] provide identical mechanisms trends in gas phase. In gas media, hydrogen atom transfer (HAT) is more favored. On the contrary, the solvent polarity has a significant effect on the mechanism of the antioxidant activity, since the polarity of the solvent increases the contribution of the SPLET mechanism.

Revisiting the scavenging activity of glutathione: Free radicals diversity and reaction mechanisms

Glutathione (GSH) is the most abundant low-molecular-mass thiolated compound in plants and animals, highly relevant in humans since it is one of the principal antioxidant agents capable of scavenging reactive oxygen species (ROS). In addition, it has a function in the immune system and in cell proliferation, and most recently it was discovered that it works against COVID-19. Considering the high flexibility of glutathione, with an atomic configuration and charge state susceptible to minimal changes in its chemical environment, it is of relevance to ascertain what is the scavenging capacity of each of the most probable glutathione species under physiological conditions. In order to find the site and mechanism that contributes the most to the antioxidant activity of GSH, density functional theory (DFT) calculations on multiple species of this molecule were performed in this work. Reactivity indexes, related to hydrogen atom transfer (HAT), single electron transfer-proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanism were calculated for glutathione. In addition, Gibbs free energies of reaction (ΔG) were obtained for the reactions of GSH with several free radicals to confirm the thermochemical viability of each antioxidant mechanism and to avoid misleading conclusions in terms of considering energetically unfavorable reactions. The results confirm that HAT is the chemical route contributing the most to the antioxidant activity of GSH. However, at least for one radical of interest, SPLET should also be considered.

Study on structural detailing of gossypetin and its medicinal application in UV filtering, radical scavenging, and metal chelation open up through NCI, TD-DFT, QTAIM, ELF, and LOL analysis

Density functional theory (DFT) computations were used to investigate gossypetin’s antioxidant effects via •OH, •OOH, and •NO2 scavenging and Zn2+ chelation mechanisms in solvent phases. Intramolecular hydrogen bonding, which accounts for the stability of generated radicals, was explained using non-covalent interaction (NCI) analysis. Investigations have been done on three primary operating mechanisms, sequential proton loss electron transfer (SPLET), single electron transfer-proton transfer (SET-PT), and H-atom transfer (HAT). SPLET was found to be the most advantageous for •OOH, HAT for •NO2, and HAT in polar whereas SPLET in non-polar media for •OH. UV absorption in the region 200–400 nm suggests, gossypetin can act as a UV filter and the nature of excitation was described by hole-electron analysis. The interaction energy analysis predicted the best chelation site in gossypetin. The bond critical point (BCP) analysis explained the electrostatic nature of donor–acceptor interaction. The influence of explicit solvent effects is also taken into account.

Experimental evaluation of the antioxidant and antitumor activities of thyme and basil essential oils and their phenolic constituents: theoretical antioxidant evaluation

BackgroundIdentifying specific biological activities of natural products are of the main concerns worldwide for the use in safe functional food manufacture; essential oils and their components are good candidates in this respect. The present work aims to evaluate the biological activities of basil and thyme oils as well as their phenolic constituents. Using computational methods to predict biological activities are currently effective tools in minimizing and explaining experimental works.ResultsChemical composition of thyme and basil oils were determined using GC–MS. The identified phenolic components were thymol (28.21%) and carvacrol (0.47%) in thyme oil and eugenol (11.37%) in basil oil. The antioxidant activity of both oils and their phenolic constituents as expressed by EC50 value were 535.01, 134.37, 176.57, 407.89 and 2.29 µg/mL against DPPH and 131.95, 56.65, 57.15, 82.71and 32.80 µg/mL against hydrogen peroxide, respectively. The order of activity is basil oil > thyme oil while phenolic compound order is eugenol > thymol > carvacrol; reducing power showed the same order. Basil oil showed also higher and good antitumor activity where it reduces the surviving fraction to 38.4% of brain tumor cells (U251) and 61.3% of liver tumor cells (HEPG2) at concentration 10 µg/mL. The antioxidant activity were evaluated theoretically according to the main three mechanisms, Hydrogen-Atom-Transfer (HAT), Single Electron Transfer–Proton Transfer (SET-PT) and the Sequential Proton Loss Electron-Transfer (SPLET); the results proved the experimental order of antioxidant and biological activities, and explained the remarkably higher activities of basil oil and its main phenolic component, eugenol.ConclusionTheoretical calculation can be used successfully to explain and predict the experimental biological activity results. Basil oil and its main phenolic component, eugenol, were found effective as antioxidants. Basil oil was also efficient in reducing the surviving fraction of liver and brain cancer cells where it reduces brain cells even lower than cells treated by doxorubicin, a known anti-cancer agent; thus, basil oil and its main phenolic components, eugenol, can be used safely in food preservation and functional food production.Graphical

Molecular docking and A DFT study on the antiradical activity of naringenin and hesperetin with nitric oxide, peroxy, and methoxy radicals

AbstractNaturally occurring flavonoids, naringenin (N) and hesperetin (H), were theoretically investigated for their ability to scavenge nitric oxide, peroxy, and methoxy radicals in gas, water, and benzene solvent media. BMK/6‐311+G(d,p) level of theory was used to for determine antiradical activity of the selected compounds and the calculation of reaction enthalpies related to three possible mechanisms of free radical scavenging activity, namely, hydrogen atom transfer (HAT), single electron transfer–proton transfer (SET‐PT), and sequential proton loss electron transfer (SPLET). When the results were examined, it was seen that the SET‐PT mechanism was not an effective antioxidant effect mechanism in any solvent medium. In addition, in the absence of any radicals, HAT in the gas phase, SPLET in the water phase, and HAT and SPLET in the benzene phase are in competition. When the investigated antioxidants were examined in the presence of various radicals in terms of their antiradical scavenging properties, it was observed that the SET‐PT mechanism was not possible in all radicals and all solvent phases due to positive ionization potential (IP) values. In addition, it was determined that the SPLET mechanism pathway was the most likely mechanism pathway with all the radicals examined. In addition, molecular docking calculations of the studied molecules were made to compare the activities against to human peroxiredoxin‐5 (HP5), a protein with antioxidant properties.

Effect of substituent on the rate of reaction between 4Y‐ArNH2 (Y = H, F, Cl, CH3, OCH3, NH2, N(CH3)2, CF3, CN, NO2) with CH3OO• in the gas phase

AbstractEffect of substituent (Y), including halogen (F and Cl), electron donating (ED) and electron withdrawing (EW) group on the thermoparameters and kinetic behavior of reactions between 4Y‐ArNH2 and CH3OO• was computationally studied using density functional theory (DFT) at M05‐2X/6‐311++G(d,p) method in combination with the transition state theory (TST) in Eyringpy program. Based on the three mechanisms of reaction between 4Y‐ArNH2 and CH3COO•, namely the hydrogen transfer (HAT/PCET), single electron transfer ‐ proton transfer (SET‐PT), and sequential proton loss electron transfer (SPLET), the effects on the thermoparameters involved in these mechanisms were investigated. ED group reduces the bond dissociation energy (BDE) and ionization energy (IE) then also increases the rate of hydrogen transfer reaction of 4Y‐ArNH2 and CH3OO•. Hydrogen atom transfer reaction of ArNH2 with CH3OO• at 298.15 K in the gas phase preferably takes place via PCET with the rate constant kPCET of 1.19×10‐19 cm3.molecule‐1.s‐1 is higher than that of kHAT of 2.19×10‐20 cm3.molecule‐1.s‐1. The rate constants of all 4Y‐ArNH2 + CH3OO• reactions were also reported and PCET mechanism is dominated with the branching ratio (Γ%) ranging from 73 % to 95 %.

Antioxidant Potential of Santowhite as Synthetic and Ascorbic Acid as Natural Polymer Additives.

A wide variety of additives are used to improve specific characteristics of the final polymeric product. Antioxidant additives (AAs) can prevent oxidative stress and thus the damage of polymeric materials. In this work, the antioxidant potential and thus the applicability of Santowhite (SW) as synthetic and ascorbic acid (Asc) as natural AAs were explored by using computational tools. Two density functional theory (DFT) methods, M05-2X and M06-2X, have been applied in combination with the 6-311++G(2d,2p) basis set in gas phase. Three antioxidant mechanisms have been considered: hydrogen atom transfer (HAT), single electron transfer-proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). Bond dissociation enthalpy (BDE), ionization potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA), and electron transfer enthalpy (ETE) have been computed for each potential hydrogen donor site. The results indicate that the antioxidant potential of Asc is higher than SW. Furthermore, some of the C-H bonds, depending on their position in the structures, are potent radical scavengers, but O-H groups are more prone to donate H-atoms to free radicals. Nonetheless, both additives can be potentially applied to safeguard common polymers and prohibit oxidative stress-induced material deterioration.

Phenolic acids and their carboxylate anions: Thermodynamics of primary antioxidant action

Phenolic acids represent naturally occurring antioxidants and play important role in free radicals scavenging. In this work, we have studied thermodynamics of the first step of primary antioxidant action for phenolic OH groups of benzoic and cinnamic acid derivatives, and their carboxylate anions. M06–2X/6–311++G(d,p) reaction enthalpies related to Hydrogen Atom Transfer (HAT), Single Electron Transfer – Proton Transfer (SET-PT), and Sequential Proton-Loss Electron-Transfer (SPLET) mechanisms were computed for model non-polar environment (benzene) and aqueous solution. The effect of acid structure on found reaction enthalpies was investigated, as well. For HAT, representing relevant reaction path in both environments, the lowest O–H bond dissociation enthalpies, BDE, were found for sinapic acid (347 kJ mol−1 in benzene and 337 kJ mol−1 in water). With two exceptions, carboxylate anions show lower BDEs than parent acids. In aqueous solution, enthalpies of the first step of SPLET from phenolic OH groups are low (135–199 kJ mol−1). It indicates thermodynamic feasibility of the mechanism for acids, as well as their carboxylate anions. Although enthalpies of electron transfer from dianions formed after successive deprotonations of carboxyl and phenolic groups in water are usually higher than BDEs, differences are within 25 kJ mol−1. Demethylation of OCH3 groups may affect radical scavenging activity of studied substances due to O–CH3 BDE considerably lower (230–269 kJ mol−1) in comparison to O–H ones.

Computational study of synthetic and natural polymer additives — Antioxidant potential of BHA, TBHQ, BHT, and curcumin

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.

Antioxidant activity of erlotinib and gefitinib: theoretical and experimental insights

Erlotinib and gefitinib are quinazoline derivatives with antineoplastic properties. Usually, intake of antineoplastic agents results in much a greater degree of oxidative stress, i.e. the production of free radicals, than induced by cancer itself. Hence, anticancerous drugs must also exhibit antioxidant activity but this has not been studied thus far. In this study, the antioxidant activity of erlotinib and gefitinib was examined by experimental and computational studies. It was found that erlotinib and gefitinib exhibit good 2,2-dipheny l-1-picrylhydrazyl (DPPH) radical and hydroxyl radical scavenging (HRS) activities. In DPPH assay, the IC50 for erlotinib and gefitinib were 0.584 and 0.696 mM, respectively, while IC50 for HRS assay were 0.843 and 1.03 mM for erlotinib and gefitinib, respectively. Structural characteristics such as frontier molecular orbitals (FMOs), molecular electrostatic potential maps (MESPs), and global descriptive parameters were calculated at DFT/B3LYP/6-311++G (d,p) on the optimized geometries of erlotinib and gefitinib. UV–visible spectroscopy revealed the possible electronic transitions between the FMOs and their associated excitation energies of both drugs and found that erlotinib has π to π* transitions while gefitinib has π to π* and σ to π* transitions. To elucidate the antioxidant activity of erlotinib and gefitinib, three mechanisms namely hydrogen atom transfer (HAT), single electron transfer proton transfer (SETPT), and sequential proton-loss electron-transfer (SPLET) were employed and articulated the results in arithmetic parameters like bond dissociation energy (BDE), proton affinity (PA), ionization potential (IP), electron transfer enthalpy (ETE), and proton dissociation enthalpy (PDE). Further, molecular docking studies have been carried out to have a better understanding of binding sites and modes of interaction with a well-known antioxidant target protein monoamine oxidase-B (MAO-B) employing docking scores and types of interactions. All the calculated parameters point out that though gefitinib and erlotinib were interchangeable, erlotinib requires a lesser amount of energy for proton transfer and electron transfer, moreover it scavenges radicals easily.

Theoretical investigations on the antioxidant potential of 2,4,5-trihydroxybutyrophenone in different solvents: A DFT approach

2,4,5-trihydroxybutyrophenone (THBP) is a synthetic molecule possessing phenolic OH groups as well as non-phenolic CHx (x = 2 and 3) groups which are believed to be responsible for its antioxidant behavior. The antioxidant nature of THBP has been systematically investigated through quantum chemical calculation by density functional theory (DFT) method with B3LYP hybrid functional and 6-311G++(d,p) basis set in gas, water and methanol media. The principal pathways such as hydrogen atom transfer (HAT), sequential proton loss electron transfer (SPLET) and single electron transfer-proton transfer (SETPT) were considered for antioxidant reactions. Changes of enthalpy (ΔH) and free energy (ΔG) were computed for OH radical scavenging by THBP. In addition, geometry, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), energy gap (Eg), the other descriptors (electron affinity (EA), ionization potential (IP), global hardness (η), softness (σ), electrophilicity (ω), chemical potential (μ), electronegativity (χ) etc.), Fukui function, molecular electrostatic potential (MEP) surface and spin density were also taken into account. The calculated data values were compared with those of gallic acid (GA), a well-recognized antioxidant, calculated at the same level and also with literature of those compounds claiming efficient antioxidant. The values of the calculated thermochemical parameters convey evidence in favor of THBP as an antiradical molecule which is strongly supported by the descriptor values. The free radical scavenging reaction may occur preferentially at 5-OH > 4-OH > α-CH2 positions of the molecule.

A DFT study on OH radical scavenging activities of eriodictyol, Isosakuranetin and pinocembrin

Flavonoids are natural compounds with antioxidant properties that have positive effects on human health, which reduce toxic effects of reactive oxygen species (ROS) and partially oxidative damage. In the work, the density functional theory (DFT/BMK) calculations were performed for antioxidant activity evaluation of pinocembrin (P), isosakuranetin (I) and eriodictyol (E). Four main mechanisms were examined: hydrogen atom transfer (HAT), radical adduct formation (RAF), single electron transfer-proton transfer (SET-PT) and Sequential proton loss electron transfer (SPLET). HAT and SPLET are thermodynamically the most probable process in gas phase and water. The three flavonoids examined + •OH HAT and RAF mechanisms for each possible location were investigated theoretically for the first time. The results were discussed by considering thermodynamic, kinetic and structural data of various reaction paths using IRC approach. Communicated by Ramaswamy H. Sarma

Theoretical investigations on the antioxidant potential of a non-phenolic compound thymoquinone: a DFT approach.

Thymoquinone (TQ) is a natural compound present in black cumin which possesses potent antioxidant activity without having any phenolic hydroxyl group which is responsible for antioxidant activity. In the present study, computational calculation based on density functional theory (DFT) was executed to assess systematically the antioxidant behavior of this compound by considering geometrical characteristics, highest occupied molecular orbital - lowest unoccupied molecular orbital (HOMO-LUMO), and molecular electrostatic potential (MEP) surface. Thermochemical parameters correlated to the leading antioxidant mechanisms such as hydrogen atom transfer (HAT), single electron transfer-proton transfer (SETPT), and sequential proton loss electron transfer (SPLET) were studied in gas and water media. In addition, the changes of thermochemical parameters such as free energy change (∆G) and enthalpy change (∆H) were computed for hydrogen abstraction (HA) from TQ to hydroxyl radical in gas and water phases to investigate its free radical scavenging potency. The low and comparable values of bond dissociation enthalpy (BDE), proton dissociation enthalpy (PDE), ionization potential (IP), proton affinity (PA), and electron transfer enthalpy (ETE) revealed the antioxidant activity. The ∆G and ∆H also indicated apposite thermodynamic evidence in favor of antiradical capability of TQ. The attack of the free radical occurred preferentially at 3CH position of the molecule.

Investigation of antioxidant activity of epigallocatechin gallate and epicatechin as compared to resveratrol and ascorbic acid: experimental and theoretical insights

Antioxidants are molecules that help the human body to fight oxidative stress caused by excess free radicals that trigger a number of diseases. Understanding the structure–activity relationship of antioxidants and their mechanisms of action is important for designing more powerful antioxidants. Polyphenols from Vitis vinifera L. have shown several biological activities among which antioxidant activity. Among polyphenolic compounds having potent biological activities, we find resveratrol (RSV) which is a stilbene and epigallocatechin gallate (EGCg) and epicatechin (EC) which are catechins or flavanols. We report here a comparative study of the antioxidant potential of EGCg and EC as compared to RSV. The most favorable mechanism by which each molecule exerts the antioxidant activity is determined. Ascorbic acid (AA) was included as a reference. DPPH and FRAP assays were used for experimental evaluation of antioxidant activity and for theoretical calculations, density functional theory (DFT) method was chosen. Three mechanisms were investigated: hydrogen atom transfer (HAT), single electron transfer-proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET). Calculated thermodynamic parameters correlate well with percentage inhibition (I%) and half maximal inhibitory concentration (IC50) values given by the DPPH test. Both experimental and theoretical approaches showed that EGCg is more potent antioxidant than EC and RSV. The most preferential sites are gallate moiety and 4′-OH in EGCg and OH sites of the B ring in EC. The pKa values confirm this finding. All proposed mechanisms are favored for EGCg, and SET-PT is preferred antioxidant mechanism for EC and it is the most suitable in the first step for RSV. Flavanols are more potent antioxidants than the stilbene, RSV.

Free Radical Scavenging Activity of Dihydrocaffeic Acid: A Quantum Chemical Approach

Based on density functional theory (DFT), to investigate relationships between the antioxidant activity and structure of dihydrocaffeic acid, quantum chemical calculation is used. The optimized structures of the neutral, radical and ionic forms have been carried out by DFT-B3LYP method with the 6-311G(d,p) basis set. Reaction enthalpies related with the hydrogen atom transfer (HAT), single electron transfer proton transfer (SET-PT) and sequential proton loss and electron transfer (SPLET) were calculated in gas and water phase. The HOMO-LUMO energy gap, electron affinity, electronegativity, ionization energy, hardness, chemical potential, global softness and global electrophilicity were calculated by using the same level of theory. Surfaces with a molecular electrostatic potential (MEP) were studied to determine the reactive sites of dihydrocaffeic acid. The difference in energy between the donor and acceptor as well as the stabilization energy was determined through the natural bond orbital (NBO) analysis. The Fukui index (FI) based on electron density was employed to predict reaction sites. Reaction enthalpies are compared with previously published data for phenol and 3,4-dihydroxycinnamic acid.

Theoretical insights on the antioxidant activity of dihydrocaffeic acid

In this work, quantum chemical analysis have been done to study the structure and antioxidant activity (AA) of dihydrocaffeic acid (DHCA) based on the density functional theory (DFT). Structural optimization and thermochemical calculations of the neutral, radical and ionic forms of DHCA have been carried out by DFT-B3LYP/6-311G(d,p) approach. Systematic study of reaction enthalpies related with the hydrogen atom transfer (HAT), single electron transfer proton transfer (SET-PT) and sequential proton loss and electron transfer (SPLET) have also been calculated in gas and water. Global Molecular Descriptors (GMD) and Non-Linear Optical (NLO) properties have been calculated by using the same theory. The interaction between donors and acceptors and stabilization energy have been determined with the help of Natural Bond Orbital (NBO) tool.

Predicting the antioxidant activity of some flavonoids of Arbutus plant: A theoretical approach

In this work, the antioxidant activity, free radical-scavenging capacity, molecular geometry and intramolecular hydrogen bonding interaction were explored for three natural flavonoid compounds of Arbutus unedo L. plant, Fisetin (3,3′,4′,7-tetrahydroxy flavone), Catechin (Flavan-3,3′,4′,5,7-pentol) and Apigenin (4′,5,7-trihydroxy flavone). Three potential mechanisms of antioxidant activity, hydrogen atom transfer (HAT), single electron transfer-proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET), have been explored. The physicochemical parameters (BDE, IP, PA, PD, ETE, HOMO and LUMO), as well spin density distribution, were calculated in different solvents. The mechanisms involved in the radical scavenging activity, taking into account the position of the most active OH hydroxyl group, are in accordance with the experimental tests. HAT mechanism is most favorable in the gas phase and benzene solvent. B-ring of the three flavonoids is the active center for the antioxidant activity. Fisetin presents the best antioxidant activity with high free radical scavenging capacity followed by Catechin and Apigenin, respectively.

DFT investigation of pachypodol for exploring anti-oxidant action – Performance of B3LYP and M06-2X

Anti-oxidant mechanism of the pachypodol is computed with the aid of density functional theory (DFT) in the light of B3LYP (B3, Lee-Yang-Parr correlation function) and M06-2X (highly parameterized, exchange correlation function) using 6-311G(d,p) basis set in the Gaussian 09 software package. This investigation aims to prove the better reaction enthalpies among hydrogen atom transfer (HAT), sequential proton-loss electron-transfer (SPLET) and single electron transfer-proton transfer (SET-PT) in gas and solvent phases with both the level of theories (B3LYP and M06-2X). The result shows that the preferred anti-oxidant mechanism is found to be HAT in both gas and solvent phases. The analysis of bond dissociation enthalpy (BDE) has been carried out in gas and solvent phases. Molecular descriptors are analyzed and computed in the light of both the level of theories. The radical scavenging of pachypodol is well established with B3LYP theory, since it yields appreciable results with respect to BDE, IP and PDE than M06-2X level of theory. Preferred electrophilic and nucleophilic sites of pachypodol are analyzed using MEP. The weak and strong intramolecular bonds are examined with the aid of NBO.