Radical Adduct Formation Mechanisms Research Articles

The degradation of methyl orange by OH radicals in aqueous environments: A DFT study on the mechanism, kinetics, temperature and pH effects

Methyl orange (MO) is extensively used in the food, textile, leather, and paper industries. As with many industrial chemicals, while primary environmental effects are documented, the secondary effects from its natural degradation have not been fully established. This study employs quantum chemical calculations to investigate the reaction of MO with HO• radicals that is a typical breakdown pathway in aqueous environments. It was found that the HO• + MO reaction in water can occur via either hydrogen transfer, single electron transfer, or radical adduct formation mechanisms, resulting in a variety of metastable intermediates and products. The calculated total rate constant (ktotal = 2.43×1010 M−1 s−1 at 298 K, pH = 9.2) is in good agreement with the experimental rate constant (kExp = (2.0 ± 0.3) ×1010 M−1 s−1at 298 K, pH = 9.2), thus confirming the accuracy of the calculation method. MO can degrade in natural water within the broad time range of 3.28 hrs to 56.6 years. The breakdown of methyl orange by HO• radicals is more effective at high temperatures and basic pH levels.

Exploring antioxidative properties of xanthohumol and isoxanthohumol: An integrated experimental and computational approach with isoxanthohumol pKa determination

This study explores the antioxidative activities of xanthohumol (XN) and isoxanthohumol (IXN), prenylated flavonoids from Humulus lupulus (family Cannabaceae), utilizing the oxygen radical absorption capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays along with computational Density Functional Theory methods. Experimentally, XN demonstrated significantly higher antioxidative capacities than IXN. Moreover, we determined IXN pKa values using the UV/Vis spectrophotometric method for the first time, facilitating its accurate computational modeling under physiological conditions. Through a thermodynamic approach, XN was found to efficiently scavenge HOO• and CH3O• radicals via Hydrogen Atom Transfer (HAT) and Radical Adduct Formation (RAF) mechanisms, while CH3OO• scavenging was feasible only through the HAT pathway. IXN exhibited its best antioxidative activity against CH3O• via both HAT and RAF mechanisms and could also scavenge HOO• through RAF. Both Single Electron Transfer (SET) and Sequential Proton Loss-Electron Transfer (SPLET) mechanisms were thermodynamically unfavorable for all radicals and both compounds.

Reaction of methylene blue with OH radicals in the aqueous environment: mechanism, kinetics, products and risk assessment.

Methylene Blue (MB) is an industrial chemical used in a broad range of applications, and hence its discharge is a concern. Yet, the environmental effects of its degradation by HO˙ radicals have not been fully studied yet. This study employs quantum chemical calculations to investigate the two-step degradation of MB by HO˙ radicals in aqueous environments. It was found that MB undergoes a rapid reaction with the HO˙ radical, with an overall rate constant of 5.51 × 109 to 2.38 × 1010 M-1 s-1 and has a rather broad lifetime range of 11.66 hours to 5.76 years in water at 273-383 K. The calculated rate constants are in good agreement with the experimental values (k calculation/k experimental = 2.62, pH > 2, 298 K) attesting to the accuracy of the calculation method. The HO˙ + MB reaction in water followed the formal hydrogen transfer and radical adduct formation mechanisms, yielding various intermediates and products. Based on standard tests these intermediates and some of the products can pose a threat to aquatic organisms, including fish, daphnia, and green algae, they have poor biodegradability and have the potential to induce developmental toxicity. Hence MB in the environment is of moderate concern depending on the ratio of safe to harmful breakdown products.

Effect of hydroxyl position on antioxidant ability of hydroxycoumarin derivatives: A theoretical investigation

Effect of the OH group position on the antioxidant ability of hydroxycoumarin derivatives (HOC) was investigated by quantum chemical computation. Frontier molecular orbitals, molecular electrostatic potential, and thermodynamic parameters were analyzed in detail. The results indicate that 3-HOC, 6-HOC, and 7-HOC exhibit as the best reactants with free radicals through analysis of global reactivity descriptor values, meanwhile H (in OH groups) of 4-HOC, 5-HOC, 6-HOC, and 7-HOC molecules are the most preferable sites for nucleophilic attacks. Besides, thermodynamic and kinetic studies reveal hydrogen atomic transfer is the primary mechanism when hydroxycoumarin derivatives react with HOO• free radical in the gas phase and pentyl ethanoate. Hydrogen atomic transfer products account for over 97 % of the total products of hydrogen atomic transfer and radical adduct formation mechanisms. According to the study, 6-HOC is the most effective scavenger of free radicals when compared to other derivatives, with a rate constant of 1.38 × 104 M−1s−1 in the gas phase and 6.5 × 103 M−1s−1 in pentyl ethanoate. The interaction of O20∙∙∙H21 in the transition state of 6-HOC is crucial in stabilizing its structure. This finding suggests that 6-HOC can be a potential candidate for developing antioxidants for various applications in the medical and industrial fields. The results of this study provide valuable insights into the mechanisms by which antioxidants can scavenge free radicals and protect against oxidative stress.

Radical Scavenging Mechanisms of 1-Arylhydrazone Benzimidazole Hybrids with Neuroprotective Activity.

Benzimidazole-arylhydrazone hybrids showed promising potential as multifunctional drugs for the treatment of neurodegenerative disorders. The neuroprotection studies conducted using an in vitro model of H2O2-induced oxidative stress on the SH-SY5Y cell line revealed a remarkable activity of the compound possessing a vanilloid structural fragment. The cell viability was preserved up to 84% and this effect was significantly higher than the one exerted by the reference compounds melatonin and rasagiline. Another compound with a catecholic moiety demonstrated the second-best neuroprotective activity. Computational studies were further conducted to characterize in depth the antioxidant properties of both compounds. The possible radical scavenging mechanisms were estimated as well as the most reactive sites through which the compounds may deactivate a variety of free radicals. Both of the compounds are able to deactivate not only the highly reactive hydroxyl radicals but also alkoxyl and hydroperoxyl radicals, following hydrogen atom transfer or radical adduct formation mechanism. In nonpolar medium, 3e is predicted to react slightly faster than 3a with alkoxyl radicals and around two orders of magnitude faster than 3a with hydroperoxyl radicals. The most reactive sites for formal hydrogen atom transfer in 3a are the meta-hydroxy group in the phenyl ring in water and the amide N-H group in benzene; in 3e, the amide N-H group is more reactive in both solvents. The radical adduct formation can occur at several positions in 3a and 3e, the most active being C4, C6, and C14. The stability of the formed radicals was estimated by NBO calculations. The NBO calculations indicated that the spin density in the radicals formed by the abstraction of a hydrogen atom from the amide groups of both compounds is delocalized over the phenyl ring and the hydrazone chain. The obtained theoretical data for the better radical scavenging ability of the vanilloid hybrid corroborate its experimentally established better neuroprotective activity.

A DFT study on the scavenging activity of curcumin toward methyl and ethyl radicals

The curcumin is a well-known antioxidant that can scavenge free radicals efficiently. The methyl free radicals, generated by the metabolism of various genotoxic compounds such as hydrazines and peroxides, can methylate various sites in DNA. Herein, we have carried out density functional theory calculations to investigate the scavenging activity of curcumin toward the methyl and ethyl radicals through radical adduct formation (RAF), hydrogen atom transfer (HAT) and single electron transfer (SET) mechanisms. The SET mechanism is found to be highly endergonic and so not viable. Our calculations show that the curcumin can scavenge methyl radicals through both RAF and HAT mechanisms but RAF would be preferred over the HAT. Further, it is found that the curcumin can scavenge methyl radicals more efficiently as compared to ethyl radicals through RAF mechanism.

Antioxidant activity of caffeic acid: thermodynamic and kinetic aspects on the oxidative degradation pathway

Caffeic acid is a phenolic secondary metabolite from plants, which is known for its antioxidant properties. The effective mitigation of methanol-induced oxidative stress by caffeic acid depends on the direct radical scavenging as well as the formation of new metabolites via oxidative degradation. Herein, thermodynamic and kinetic aspects of the oxidative degradation pathway of caffeic acid in the presence of radical CH3O• and its isomer, •CH2OH are discussed for the first time, employing density functional theory (DFT). The direct radical scavenging activity of caffeic acid against these radicals is verified via hydrogen atom transfer (HAT) and radical adduct formation (RAF) mechanisms. HAT is predicted to be more feasible than RAF mechanism as per the computed data. Additionally, energetic details of the proposed oxidative degradation pathway of radical adduct intermediates toward the formation of a cyclic metabolite is analyzed. Kinetic studies indicated a significant tunneling contribution to the H abstraction pathways having high activation barriers. Further, our results imply that the newly formed metabolites exhibit comparable antioxidant activity with that of caffeic acid.

On The Radical Scavenging and DNA Repairing Activities by Natural Oxygenated Diterpenoids: Theoretical Insights.

Diterpenoids are abundant and important compounds in Euphorbia species owing to their structural diversity; therefore, in this study, we investigate the modern-concept antioxidant activities, including free-radical scavenging and oxidative DNA damage repairing, of highly oxygenated diterpenoids originating from the aerial part of Euphorbia helioscopia. Four compounds with structural types of ent-abietane, containing a fused furan ring in their structures, including euphelionolide A (1), euphelionolide D (2), euphelionolide I (3), and euphelionolide L (4) are selected. First, the radical-scavenging activity of these compounds was evaluated with two typical radicals HOO• and HO• in water and pentyl ethanoate (PEA, to mimic lipid environment) via three main mechanisms, namely, hydrogen atom transfer (HAT), radical adduct formation (RAF), and single electron transfer. It is found that the studied compounds are able to scavenge free radicals at multiple reactive sites favorably via HAT and RAF mechanisms, in which the former dominates in the case with HOO• while both mechanisms are competitive in the reaction with HO•. Second, chemical repairing of DNA damage is modeled with the H-atom and single electron being transferred from the studied molecules to damaged 2'-deoxyguanosine (2dG) (i.e., 2dG• radicals and 2dG•+ radical cation). Among the four compounds, euphelionolide A is shown as the most effective radical scavenger and also the highest potential species for chemical repairing of radical-damaged DNA in both water and PEA.

A Computational Study of the Reactions between Dehydrozingerone Derivatives and the Hydroperoxyl Radical in Aqueous and Lipid Media

Dehydrozingerone (the half-analogue of curcumin) is a natural product that is isolated from ginger rhizomes. Recent studies have shown that this compound displays several physiological activities including antioxidant properties, and it can scavenge oxygen-free radicals like hydroxyl, peroxyl and superoxide radicals. In this work, the thermodynamic and kinetic aspects of the antiradical activity of the natural dehydrozingerone DHZ0 (R=H) and the designed derivatives DHZ1 (R=CHO), DHZ2 (R=OMe) and DHZ3 (R=NMe2) towards the hydroperoxyl radical (HOO•) were investigated at the M06-2X/6-311[Formula: see text]G([Formula: see text],[Formula: see text]) level of theory. The calculations have been performed in gas phase, pentyl ethanoate and water solvents using the implicit SMD solvation model. Four potential mechanisms have been investigated, namely, hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), sequential proton loss electron transfer (SPLET) and radical adduct formation (RAF). The obtained results show that the SET-PT and RAF mechanisms are endergonic processes and are thermodynamically disfavored, whereas the exergonic HAT process is predicted as the most thermodynamically favored mechanism in all media. The SPLET mechanism was excluded due the minor proportions of the anion species at physiological pH. Kinetic calculations show that DHZ3 reacts with HOO• 1860, 1250 and 215 times faster than DHZ0 in gas phase, pentyl ethanoate, and water, respectively. Based on thermodynamic and kinetic calculations, the designed compound DHZ3 is predicted as a good candidate for hydroperoxyl scavenging in both polar and nonpolar media. Drug likeness evaluation of the studied DHZ derivatives shows that the pharmacokinetic parameters satisfy all the Lipinski and Veber rules.

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

Antiradical Activity of Beetroot (Beta vulgaris L.) Betalains.

Flavonoids, phenolic acids, and anthocyanidins are widely studied polyphenolics owing to their antiradical activity. Recently, beetroot dyes have drawn an attention as possible radical scavengers, but scant information can be found on this topic. In this study selected compounds were investigated using computational chemistry methods. Implicit water at physiological pH was chosen as the environment of interest. Betalains’ dissociation process and electronic structure were examined, as well as the reactivity in six pathways against some common radicals, such as hydroxyl, hydroperoxide, superoxide, and nitric oxide. The study showed that all carboxyl groups are dissociated in the given conditions. The dissociation process impacts the electronic structure, which has consequences for the overall activity. Highly stabilized conjugated structures favor the electron–accepting type of scavenging reactions, primarily by a radical adduct formation mechanism. Betanidin and indicaxanthin were found to be the most promising of the compounds studied. Nevertheless, the study established the role of betalains as powerful antiradical dietary agents.

Kinetics and mechanism of reactive radical mediated fluconazole degradation by the UV/chlorine process: Experimental and theoretical studies

The emerging organic contaminants can be effectively removed in the UV/chlorine process by produced hydroxyl radical (HO) and chlorine-derived radicals (Cl, ClO, etc.). However, the degradation mechanism and pathways of reactive radical reaction with contaminants are still unclear. Here we investigated the reactive radical mediated reaction kinetics and mechanism of fluconazole in UV/chlorine process using theoretical calculations and experimental studies. The results showed that fluconazole could be degraded effectively by UV/chlorine treatment than by UV photolysis and chlorination alone. The Cl and HO were found to play a major role in degradation of fluconazole by hydrogen atom transfer and radical adduct formation mechanisms, respectively. The single-electron transfer pathway of Cl, HO and ClO seems to be impossible due to the high free energy barriers of 21.87 kcal mol−1, 35.12 kcal mol−1 and 46.05 kcal mol−1, respectively. Six transformation products were identified by high resolution mass spectrometry and they were formed via fluconazole de-fluorination, hydroxylation, cleavage and cyclization with the triazole ring. The water quality parameters such as pH and coexisting components (DOM, HCO3−/CO32−) could influence the removal of fluconazole in UV/chlorine process by impacting the generation of reactive radicals. The toxicity of fluconazole to aquatic organisms can be decreased by UV/chlorine process, and only trace amounts of chloroform were detected.

Is Usnic Acid a Promising Radical Scavenger?

Usnic acid (UA) is a natural product found in the lichen genera. Because of the phenolic groups in its structure, UA is suspected to be an antioxidant. Therefore, in this study, the radical scavenging of UA was investigated in physiological environments in silico by using kinetic calculations. It was found that the overall rate constant for the hydroxyl radical scavenging activity was approximately 109 M–1 s–1 in all environments, whereas the HOO• and CH3OO• radical scavenging activities were only significant in the polar environments with k in the range of 103–104 M–1 s–1. The results also revealed that the HO• scavenging activity followed the single electron transfer (SET) and radical adduct formation mechanisms; however, the SET pathway (for the dianion HU2–) played a dominant role in the scavenging of other studied radicals, including CH3O•, CCl3O•, CCl3OO•, NO2, SO4•–, and N3•. The activity of UA against these radicals was as high as that of typical phenolic acids such as ferulic acid, p-coumaric acid, caffeic acid, dihydrocaffeic acid, and sinapinic acid (kf ∼ 108 M–1 s–1) in polar solvents. Thus, UA is a promising natural antioxidant in aqueous environments.

Antioxidative Action of Ellagic Acid-A Kinetic DFT Study.

Although one can find numerous studies devoted to the investigation of antioxidative activity of ellagic acid (EA) in the scientific literature, the mechanisms of its action have not yet been fully clarified. Therefore, further kinetic studies are needed to understand its antioxidative capacity completely. This work aims to reveal the underlying molecular mechanisms responsible for the antioxidative action of EA. For this purpose, its reactions with HO• and CCl3OO• radicals were simulated at physiological conditions using the quantum mechanics-based test for overall free-radical scavenging activity. The density functional theory in combination with the conductor-like polarizable continuum solvation model was utilized. With HO• radical EA conforms to the hydrogen atom transfer and radical adduct formation mechanisms, whereas sequential proton loss electron transfer mechanism is responsible for scavenging of CCl3OO• radical. In addition, compared to trolox, EA was found more reactive toward HO•, but less reactive toward CCl3OO•. The calculated rate constants for the reactions of EA with both free radicals are in a very good agreement with the corresponding experimental values.

Insight into Antioxidant and Photoprotective Properties of Natural Compounds from Marine Fungus.

This computational and experimental work aims to elucidate physicochemical and photophysical natures of free radical scavenging and ultraviolet radiation (UVR) filtering activities of five terpenoids available in the extract of marine fungus. The antioxidant activities of ochraceopone F (C1), aspertetranone D (C2), cycloechinulin (C3), wasabidienone E (C4), and mactanamide (C5) are evaluated by using density functional theory (DFT) at the M05-2X/6-311++G(d,p) level of theory in the gas phase, water, and pentyl ethanoate (PEA). Double antioxidant mechanisms allowing the second (H+/e-) donation such as double hydrogen atom transfer (dHAT), double single electron transfer-proton transfer (dSET-PT), and double sequential proton loss-electron transfer (dSPL-ET) are considered. Reaction enthalpies (ΔrH0), standard Gibbs free energies (ΔrG0) and potential energy surfaces of reactions toward HOO• radical are then established to evaluate the hydrogen transfer (HT) and radical adduct formation (RAF) mechanisms. The computational results are supported by DPPH• and ABTS•+ antioxidant essays. Results show that all compounds C1-C5 are able to scavenge two free radicals via dHAT, dSET-PT, and dSPL-ET mechanisms. Among the compounds, C3 and C4 represent the most potential antioxidants, especially via HAT and RAF mechanisms in all the reaction media. Their rate constants for both HAT and RAF reactions are remarkably higher than that of Trolox and ascorbic acid. The kinetic calculations on activation Gibbs free energies (ΔG⧧) and rate constants (kTST) based on conventional transition state theory (TST) reveal that HAT and RAF processes are in competition in solvents. Photophysical processes occurring during UVR exposure are investigated using the time dependent density functional theory (TD-DFT) combined with UV-vis experiments. The obtained results highlight the promising activities of C1-C5 in UVR absorption in the ranges of UVA and UVB. Among them, C3 and C4 also show better UV absorption properties with the easiest excitations (band gaps equal to 4.06 and 3.65 eV). This study suggests the natural candidates possibly used in organic sunscreen.

Unraveling the antioxidant potential of thiamine: Thermochemical and kinetics studies in aqueous phase using DFT

AbstractThe scavenging mechanism of thiamine (or vitamin B1) towards HO• and HOO• radicals has been revisited using density functional theory (DFT) at the M05‐2X/6‐311++G (d,p) level of theory. Enthalpies and Gibbs free energies of four common antioxidant reactions, i.e. formal hydrogen transfer (FHT), proton transfer (PT), single electron transfer (SET) and radical adduct formation (RAF), have been systematically calculated in the aqueous phase. Potential energy profiles accompanied with the optimized structures of all transition states (TS) and intermediate ones were also established. As a result, thiamine represents as a potent antioxidant notably via RAF mechanism with the lowest ΔH0 values at C12 position equal to ‐37.5 and ‐9.2 kcal/mol towards HO• and HOO• radicals, respectively. The reactions are also favorable with ΔG0 values of ‐28.8 and 2.8 kcal/mol, respectively. The order of the decrease in preponderance of the studied mechanism is as follows: RAF > FHT > SET > PT. The scavenging reactivity towards HO• radical is considerably higher than the one toward HOO• radical as expected. In comparing with trolox and ascorbic acid, their antioxidant potential could be classified in the decreasing order: ascorbic acid > thiamine > trolox.

A quantum chemical study on the reactivity of four licorice flavonoids scavenging ·OOCl3C

Isoliquiritigenin, liquiritigen, uralenol, and neouralenol are four natural licorice flavonoid compounds extracted from licorice, which have the ability of scavenging free radicals. In this paper, the density functional theory (DFT) was used to study the microscopic reaction mechanism of the four kinds of licorice flavonoids respectively scavenging ·OOCl3C in vivo. At the level of M06-2X/6-311+G(d,p), the geometries of all stationary points for hydrogen atom transfer (HAT) and radical adduct formation (RAF) pathways were optimized. The thermodynamic parameters and kinetic parameters of each reaction pathway were obtained, and the potential energy surface information of each reaction pathway was obtained too. Using the continuum solvation model based on solute electron density (SMD), the influence of the solvation effect on the reaction was calculated. The main mechanisms and reactive sites for the capture of ·OOCl3C by four licorice flavonoids, liquiritigen, isoliquiritigenin, uralenol, and neouralenol, were determined. Research indicates liquiritigen captures ·OOCl3C by HAT mechanism. The HAT pathway on the B′ ring of liquiritigen is the main reactive site. Isoliquiritigenin captures ·OOCl3C in the body through HAT and RAF mechanism. The RAF pathway is the dominant reaction pathway. The C1 site on the carbon–carbon double bond linking the two benzene rings is the main reactive site. Uralenol and neouralenol capture ·OOCl3C by HAT mechanism. The main reactive site of uralenol is B6 site, and the main reactive site of neouralenol is B′ 2 site. By this study, the potential energy surface information difficult to capture by experimental research is obtained, which provides a reliable theoretical basis for the further screening of highly active natural free radical scavengers of flavonoids in licorice and provides the support for the improvement of the development and application technology of licorice.

Radical Scavenging Activity of Natural-Based Cassaine Diterpenoid Amides and Amines.

The radical scavenging capacities of four new cassaine diterpenoid amides including 3β-hydroxydinorerythrosuamide (1), 3β-acetoxydinorerythrosuamide (2), 3β-tigloyloxydinorerythrosuamide (3), and 6α-hydroxydinorcassamide (4) present in leaf extract and four new cassaine diterpenoid amines namely erythroformine A (5), erythroformine B (6), 6α-hydroxy-nor-cassamine (7), and nor-erythrosuamine (8) recently identified in the extract of the bark of Erythrophleum fordii were elucidated using density functional theory (DFT) method. Different thermochemical properties characterizing antioxidant potential including bond dissociation enthalpy (BDE), proton affinity (PA), and adiabatic ionization potential (IP) were calculated at the B3LYP/6-311G(d,p) level of theory. Scavenging reaction mechanisms of cassaine diterpenes toward HOO• radical including formal hydrogen transfer (FHT; either hydrogen atom transfer (HAT) or proton coupled electron transfer (PCET)), radical adduct formation (RAF), single electron transfer (SET), and proton transfer (PT) were studied in the gas phase, water, and benzene. The potential energy profiles and kinetic calculations for the FHT and RAF reactions were calculated at 298.15 K. The results showed that all the studied compounds present strong antioxidant activity via HAT mechanism with BDEs varying from 69.4 to 77.9 kcal/mol. While solvents have only a slight effect on HAT and RAF mechanisms, SET and PT reactions are likely to occur in polar media. Among the studied compounds, 3 is the most reactive one both for HAT (H-abstraction at C7, Δ H -11.3 kcal/mol) and for RAF (radical addition at C13 = C15 bond, Δ H -5.2 kcal/mol) reactions. The rate constants of these reactions are also comparable with several referenced antioxidants such as Trolox and ascorbic acid.

Intrinsic Antioxidant Potential of the Aminoindole Structure: A Computational Kinetics Study of Tryptamine

A computational kinetics study of the antioxidant activity of tryptamine toward HO• and HOO• radicals in water at 298 K has been carried out. Density functional methods have been employed for the quantum chemical calculations, and the conventional transition state theory was used for rate constant evaluation. Different mechanisms have been considered: radical adduct formation (RAF), single electron transfer (SET), and hydrogen atom transfer (HAT). For the reaction of tryptamine with the hydroxyl radical, nearly all channels are diffusion-controlled, and the overall rate constant is very high, 6.29 × 1010 M-1 s-1. The RAF mechanism has a branching ratio of 55%, followed by the HAT mechanism (31%), whereas the SET mechanism accounts just for 13% of the products. The less hindered carbon atom neighboring to the nitrogen of the indole ring seems to be the preferred site for the RAF mechanism, with a branching ratio of 16%. The overall rate constant for the reaction of tryptamine with the HOO• radical is 3.71 × 104 M-1 s-1, suggesting that it could be a competitive process with other reactions of hydroperoxyl radicals in biological environments. For this reaction only the HAT mechanism seems viable. Furthermore, only two centers may contribute to the HAT mechanism, the nitrogen atom of the indole ring and a carbon atom of the aminoethyl chain, the former accounting for more than 91% of the total products. Our results suggest that tryptamine could have a noticeable scavenging activity toward radicals, and that this activity is mainly related to the nitrogen atom of the indole ring, thus showing the relevance of their behavior in the study of aminoindoles.

Reactivity of chlorogenic acid toward hydroxyl and methyl peroxy radicals relative to trolox in nonpolar media

The quantum mechanics-based test for overall free-radical scavenging activity was applied for the investigation of antioxidative capacity of chlorogenic acid (5-O-caffeoylquinic acid, 5CQA) relative to trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, Tx) as a reference compound. Hydrogen atom transfer (HAT), radical adduct formation (RAF), electron transfer (ET), and proton loss (PL) reactions of 5CQA and Tx with HO• and CH3OO• radicals in benzene and pentyl ethanoate were examined. For this purpose, two theoretical models, M06-2X/6-311++G(d,p) in combination with the CPCM solvation model, and M05-2X/6-311++G(d,p) in combination with the SMD solvation model, were employed. It was found that M05-2X/6-311++G(d,p)—SMD failed to evaluate the influence of pentyl ethanoate, whereas M06-2X—CPCM in benzene and pentyl ethanoate and M05-2X—SMD in benzene proved to be operative and showed similar trends. Both compounds can react with HO• via HAT and RAF mechanisms, whereas HAT is the only reaction pathway with CH3OO•. 5CQA is more efficient scavenger of HO• than Tx, but less efficient scavenger of CH3OO•. Less reactive free radicals are more suitable for the determination of antioxidative activity of a compound relative to Tx. Highly reactive free radicals need to be included in the investigation of all potential reaction pathways of the compound, in which case the results from different approaches can be inconsistent.