Autoxidation Research Articles

Computational Optimization of Bioanalytical Parameters for the Evaluation of the Toxicity of the Phytomarker 1,4 Napthoquinone and its Metabolite 1,2,4-trihydroxynapththalene

Objectives:Lawsone (1,4 naphthoquinone) is a non redox cycling compound that can be catalyzed by DT diaphorase (DTD) into 1,2,4-trihydroxynaphthalene (THN), which can generate reactive oxygen species by auto oxidation. The purpose of this study was to evaluate the toxicity of the phytomarker 1,4 naphthoquinone and its metabolite THN by using the molecular docking program AutoDock 4.Methods:The 3D structure of ligands such as hydrogen peroxide (H2O2), nitric oxide synthase (NOS), catalase (CAT), glutathione (GSH), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) were drawn using hyperchem drawing tools and minimizing the energy of all pdb files with the help of hyperchem by MM+ followed by a semi-empirical (PM3) method. The docking process was studied with ligand molecules to identify suitable dockings at protein binding sites through annealing and genetic simulation algorithms. The program auto dock tools (ADT) was released as an extension suite to the python molecular viewer used to prepare proteins and ligands. Grids centered on active sites were obtained with spacings of 54 × 55 × 56, and a grid spacing of 0.503 was calculated. Comparisons of Global and Local Search Methods in Drug Docking were adopted to determine parameters; a maximum number of 250,000 energy evaluations, a maximum number of generations of 27,000, and mutation and crossover rates of 0.02 and 0.8 were used. The number of docking runs was set to 10.Results:Lawsone and THN can be considered to efficiently bind with NOS, CAT, GSH, GR, G6PDH and NADPH, which has been confirmed through hydrogen bond affinity with the respective amino acids.Conclusion:Naphthoquinone derivatives of lawsone, which can be metabolized into THN by a catalyst DTD, were examined. Lawsone and THN were found to be identically potent molecules for their affinities for selected proteins.

Comparative study on the free radical scavenging mechanism exerted by geraniol and geranylacetone using the combined experimental and theoretical approach

AbstractIn the current study the free radical scavenging mechanism of geraniol and geranylacetone has been investigated experimentally and theoretically. Two fragrant acyclic terpenoids were subjected to the ABTS and DPPH assay. Furthermore, the detailed quantum chemical calculations have been undertaken in order to evaluate the possible pathways underlying the radical scavenging activity of selected compounds in the non‐polar and polar media. The density functional theory (DFT) using the hybrid Becke three‐parameter exchange‐correlation functional (B3LYP) was applied. In general both investigated compounds possessed very weak anti‐radical activity at the applied experimental conditions but geranylacetone was significantly more effective as a ABTS•+ and DPPH• scavenger than geraniol. The comparison of DFT‐predicted reaction enthalpies associated with the hydrogen atom transfer mechanism (HAT), the single electron and proton transfer process (SET‐PT) and the sequential proton loss electron‐transfer (SPLET), revealed that the former mechanism should be favoured in geraniol solvated in both the non‐polar and polar media. On the contrary, an anti‐radical activity of geranylacetone in the non‐polar solvent was ascribed to the hydrogen donation mechanism while in the polar solvent it was assigned to the SPLET. According to the computational results the presence of allylic H‐atom (at the position 1C) close to the –OH group seemed to be essential for the observed anti‐radical activity of geraniol. The scavenging ability of geranylacetone was associated with the presence of both allylic and alkylic hydrogens in the close vicinity of the carbonyl functionality. Copyright © 2015 John Wiley & Sons, Ltd.

Copolymerization of Limonene with n‐Butyl Acrylate

The bulk free radical copolymerization of d‐limonene (Lim) with n‐butyl acrylate (BA) was carried out at 80 °C using benzoyl peroxide as initiator. Low conversion experiments were run to estimate the copolymer reactivity ratios as rBA = 6.07 and rLim = 0.0067. High conversion experiments were then conducted to validate the reactivity ratios for prediction of cumulative copolymer composition. The presence of allylic hydrogen in d‐limonene caused a notable degradative chain transfer reaction which greatly impeded polymerization. Increasing d‐limonene fractions in the copolymer resulted in a decrease in final conversion and molecular weight, and an increase in glass transition temperature.

ChemInform Abstract: Catalytic 1,4‐Rhodium(III) Migration Enables 1,3‐Enynes to Function as One‐Carbon Oxidative Annulation Partners in C—H Functionalizations.

AbstractAn unexpected mode of oxidative annulation in Rh‐catalyzed C‐H functionalizations of arenes having hydroxy‐substituted functionalities with 1,3‐enynes containing allylic hydrogens cis to the alkynes is described.

Mechanism of Hop-Derived Terpenes Oxidation in Beer

Terpenes are the main constituents of hops essentiol oil and contribute to the singular sensory properties of beer. However, terpenes are sensitive to oxidation leading to quality loss during beer aging. Herein, the reactivity of terpenes towards 1-hydroxyethyl radical has been determined employing a competitive kinetic approach using the spin-trap α-(4-pyridyl-1-oxide)- N-tert-butylnitrone (4-POBN). The apparent rate constant (kapp) for the reaction of terpenes with 1-hydroxyethyl radical ranges from (3.9 ± 0.2) × 105 to (1.5 ± 0.2) × 107 L mol−1 s−1 for β-pinene and terpinolene, respectively. The reaction involves hydrogen atom transfer from the terpene to 1-hydroxyethyl radical rather than electron-transfer and the rate constant is shown to be dependent on the number of allylic and benzylic hydrogen atoms and on the value of the bond dissociation enthalpy for the weakest C−H bond. The results provide a better understanding on the mechanism behind terpene decomposition in beer brewing and aging process and may further contibute to improve the oxidative stability of the herb-flavored beverages.

The role of peroxyl radicals in polyester degradation--a mass spectrometric product and kinetic study using the distonic radical ion approach.

Mass spectrometric techniques were used to obtain detailed insight into the reactions of peroxyl radicals with model systems of (damaged) polyesters. Using a distonic radical ion approach, it was shown that N-methylpyridinium peroxyl radical cations, Pyr(+)OO˙, do not react with non-activated C-H bonds typically present in polyesters that resist degradation. Structural damage in the polymer, for example small amounts of alkene moieties formed during the manufacturing process, is required to enable reaction with Pyr(+)OO˙, which proceeds with high preference through addition to the π system rather than via allylic hydrogen atom abstraction (kadd/kHAT > 20 for internal alkenes). This is due to the very fast and strongly exothermic subsequent fragmentation of the peroxyl-alkene radical adduct to epoxides and highly reactive Pyr(+)O˙, which both could promote further degradation of the polymer through non-radical and radical pathways. This work provides essential experimental support that the basic autoxidation mechanism is a too simplistic model to rationalize radical mediated degradation of polymers under ambient conditions.

ChemInform Abstract: Synthesis of Cyclobutenes and Allenes by Cobalt‐Catalyzed Cross‐Dimerization of Simple Alkenes with 1,3‐Enynes.

Cobalt-catalyzed cross-dimerization of simple alkenes with 1,3-enynes is reported. A [2+2] cycloaddition reaction occurred, with alkenes bearing no allylic hydrogen, by reductive elimination of a η(3)-butadienyl cobaltacycle. On the other hand, aliphatic alkenes underwent 1,4-hydroallylation by means of exo-cyclic β-H elimination. These reactions can provide cyclobutenes and allenes that were previously difficult to access, from simple substrates in a highly chemo- and regioselective manner.

Catalytic 1,4‐Rhodium(III) Migration Enables 1,3‐Enynes to Function as One‐Carbon Oxidative Annulation Partners in CH Functionalizations

Abstract1,3‐Enynes containing allylic hydrogens cis to the alkyne are shown to act as one‐carbon partners, rather than two‐carbon partners, in various rhodium‐catalyzed oxidative annulations. The mechanism of these unexpected transformations is proposed to occur through double CH activation, involving a hitherto rare example of the 1,4‐migration of a RhIII species. This phenomenon is general across a variety of substrates, and provides a diverse range of heterocyclic products.

Catalytic 1,4-rhodium(III) migration enables 1,3-enynes to function as one-carbon oxidative annulation partners in C-H functionalizations.

1,3-Enynes containing allylic hydrogens cis to the alkyne are shown to act as one-carbon partners, rather than two-carbon partners, in various rhodium-catalyzed oxidative annulations. The mechanism of these unexpected transformations is proposed to occur through double C–H activation, involving a hitherto rare example of the 1,4-migration of a RhIII species. This phenomenon is general across a variety of substrates, and provides a diverse range of heterocyclic products.

Sustainable polymer latexes based on linoleic acid for coatings applications

Abstract The synthesis of new waterborne polymer latexes based on renewable linoleic acid (LA) was investigated. Methacrylic functionality was incorporated into the LA and the resulting monomer was successfully polymerized via miniemulsion polymerization. The effect of the initiator amount and type on microstructure was analyzed. Almost totally converted latexes with different microstructures were achieved. Furthermore, the effect of the presence of labile allylic hydrogens on the LA backbone was discussed in terms of microstructural properties, as well as final film properties. The results suggested that LA based latexes have great potential to replace petroleum based waterborne coating materials.

The first step of biodiesel autoxidation by differential scanning calorimetry and DFT calculations

The radical abstraction reaction of (bis)-allylic hydrogen in biodiesel fatty acid chains is the first step of autoxidation, being the rate-determining one. Some intrinsic features of the intermediary radicals can determine the oxidative stability (OS) under thermodynamic control. In the present study, some common fatty acid methyl esters present in biodiesel (stearate, oleate, ricinoleate, and linoleate) were oxidized in non-isothermal conditions, using differential scanning calorimetry, and the results were compared with quantum chemical calculations at the density functional theory level. The OS order (saturated > monounsaturated > polyunsaturated) was observed in both approaches (experimental and theoretical). A slight deviation observed between oleate and ricinoleate OS’s was explained based on their allylic radicals resonance and the influence of vicinal hydroxyl group. A linear relationship was found between oxidation temperature by pressurized differential scanning calorimetry and the calculated bond dissociation energy (C–H) for the first step of autoxidation.

Synthesis of cyclobutenes and allenes by cobalt-catalyzed cross-dimerization of simple alkenes with 1,3-enynes.

Cobalt-catalyzed cross-dimerization of simple alkenes with 1,3-enynes is reported. A [2+2] cycloaddition reaction occurred, with alkenes bearing no allylic hydrogen, by reductive elimination of a η(3)-butadienyl cobaltacycle. On the other hand, aliphatic alkenes underwent 1,4-hydroallylation by means of exo-cyclic β-H elimination. These reactions can provide cyclobutenes and allenes that were previously difficult to access, from simple substrates in a highly chemo- and regioselective manner.

Gallic acid functions as a TRPA1 antagonist with relevant antinociceptive and antiedematogenic effects in mice.

The transient receptor potential ankyrin 1 (TRPA1) has been identified as a relevant target for the development of novel analgesics. Gallic acid (GA) is a polyphenolic compound commonly found in green tea and various berries and possesses a wide range of biological activities. The goal of this study was to identify GA as a TRPA1 antagonist and observe its antinociceptive effects in different pain models. First, we evaluated the ability of GA to affect cinnamaldehyde-induced calcium influx. Then, we observed the antinociceptive and antiedematogenic effects of GA (3-100 mg/kg) oral administration after the intraplantar (i.pl.) injection of TRPA1 agonists (allyl isothiocyanate, cinnamaldehyde, or hydrogen peroxide-H2O2) in either an inflammatory pain model (carrageenan i.pl. injection) or a neuropathic pain model (chronic constriction injury) in male Swiss mice (25-35 g). GA reduced the calcium influx mediated by TRPA1 activation. Moreover, the oral administration of GA decreased the spontaneous nociception triggered by allyl isothiocyanate, cinnamaldehyde, and H2O2. Carrageenan-induced allodynia and edema were largely reduced by the pretreatment with GA. Moreover, the administration of GA was also capable of decreasing cold and mechanical allodynia in a neuropathic pain model. Finally, GA was absorbed after oral administration and did not produce any detectable side effects. In conclusion, we found that GA is a TRPA1 antagonist with antinociceptive properties in relevant models of clinical pain without detectable side effects, which makes it a good candidate for the treatment of painful conditions.

Avaliação da estabilidade foto-oxidativa dos óleos de canola e de milho em presença de antioxidantes sintéticos

A estabilidade dos óleos vegetais à oxidação depende do equilíbrio entre a composição e a presença de pró-oxidantes e antioxidantes. O objetivo deste estudo consistiu em avaliar o efeito da presença de antioxidantes sintéticos durante o processo de foto-oxidação dos óleos de canola e milho. As amostras dos óleos de canola e milho em presença e em ausência dos antioxidantes butil-hidroxitolueno (BHA), propil galato (PG) e terc butil-hidroquinona (TBHQ), foram submetidas ao estresse foto-oxidativo. A reação de foto-oxidação seguiu uma cinética de primeira ordem. A constante de velocidade no período de 20 dias de foto-oxidação evidenciou que o antioxidante PG apresentou maior efeito protetor para o óleo de canola e o TBHQ para o óleo de milho. A partir dos dados de UV e RMN de ¹H, no período de 60 dias, constatou-se que os três antioxidantes apresentaram um efeito protetor a foto-oxidação. Os dados de UV evidenciaram aumento de absorção da banda em 232 nm devido à foto-oxidação e formação de dienos conjugados. A redução da intensidade de absorção desta banda na foto-oxidação com o tempo de exposição revelou que a proteção, tanto para o óleo de canola como para o de milho, foi mais efetiva com o antioxidante PG. Os índices de oxidação Roa e fração residual de hidrogênios (H) dialílicos, alílicos e vinílicos também evidenciaram que o antioxidante PG apresentou o melhor desempenho na proteção dos dois tipos de óleo.

Free Radical Metabolism of Methyleugenol and Related Compounds

Methyleugenol, the methyl ether of eugenol, both of which are flavorant constituents of spices, has been listed by the National Toxicology Program’s Report on Carcinogens as reasonably anticipated to be a human carcinogen. This finding is based on the observation of increased incidence of malignant tumors at multiple tissue sites in experimental animals of different species. By contrast, eugenol is not listed. In this study, we show that both methyleugenol and eugenol readily undergo peroxidative metabolism in vitro to form free radicals with large hyperfine interactions of the methylene allylic hydrogen atoms. These large hyperfine splittings indicate large electron densities adjacent to those hydrogen atoms. Methyleugenol undergoes autoxidation such that the commercial product contains 10–30 mg/L hydroperoxide and is capable of activating peroxidases without the presence of added hydrogen peroxide. Additionally, the hydroperoxide is not a good substrate for catalase, which demonstrates that these antioxidant defenses will not be effective in protecting against methyleugenol exposure.

Extraction of Antioxidants from Fruit Peels and its Utilization in Paneer

Natural antioxidants have gained considerable interest in recent years for their role in preventing the auto oxidation of fats, oils and fat containing food products. In the present study, peels of pomegranate, lemon and orange were used as sources of natural antioxidants. Among the three extracts pomegranate exhibited a high percentage of antioxidant activity and phenolic content of 92.7%, 249.41 mg/g in comparison to lemon and orange peel extract. Maximum total phenolic content was found in lemon extract (0.9 mg/g). Paneer samples prepared by addition of natural antioxidant extracts from these peels where subjected to sensory studies which showed that the extracts at the level of 2% was acceptable and had greater ability to prevent peroxide formation. The ability to prevent peroxide formation in paneer sample was in the order of pomegranate peel> lemon peel> orange peel. Synthetic antioxidants generally used in food products like BHT and BHA are toxic and may cause health hazards. Fruit peels like pomegranate, lemon and orange are normally wasted during fruit processing thus a proper waste utilization of these peels were done. Natural antioxidants from these peels were extracted and then utilized in paneer to increase their shelf life by preventing peroxide formation. Thus these natural antioxidants could be added to any food product containing fat and oil to increase their shelf life by preventing rancidity.

The aromatic ene reaction

The ene reaction is a pericyclic process in which an alkene having an allylic hydrogen atom (the ene donor) reacts with a second unsaturated species (the enophile) to form a new product with a transposed π-bond. The aromatic ene reaction, in which the alkene component is embedded in an aromatic ring, has only been reported in a few (four) instances and has proceeded in low yield (≤6%). Here we show efficient aromatic ene reactions in which a thermally generated aryne engages a pendant m-alkylarene substituent to produce a dearomatized isotoluene, itself another versatile but rare reactive intermediate. Our experiments were guided by computational studies that revealed structural features conducive to the aromatic ene process. We proceeded to identify a cascade comprising three reactions: (i) hexadehydro-Diels-Alder (for aryne generation), (ii) intramolecular aromatic ene, and (iii) bimolecular Alder ene. The power of this cascade is evident from the structural complexity of the final products, the considerable scope, and the overall efficiency of these multi-stage, reagent- and byproduct-free, single-pot transformations.

Synthesis of a novel diene from a cyclobutane precursor: an entry to 2,9-disubstituted [2]diadamantanes

In the gas-phase thermolysis (350 °C) of heptacyclic cyclobutane 2, n=1, (the [2+2] dimer of noradamantene) two isomeric dienes (the symmetric 5, n=1 and the asymmetric 6a) and the reduction product [2]diadamantane (7-H) are formed. Computations suggest that at 350 °C a diradical intermediate (8, n=1, derived from C–C bond cleavage of 2, n=1) gives rise to 5, n=1. Diradical 8, n=1 is also likely to abstract allylic hydrogens from 5, n=1 affording 7-H, and also to isomerize 5, n=1 to give the diene 6b from which 6a can result as the more stable diene of a Cope rearrangement. The gas-phase thermolysis of 2, n=1, in the presence of iodine affords 7-H at 350 °C and the new compound 2,9-diiodo-[2]diadamantane (7-I2) at 150 °C. 7-I2 can be easily prepared at room temperature by the iodination of 2, n=1 in CH2Cl2 and affords in a synthetically useful way diene 5, n=1 by reduction with Na/Hg at room temperature.

Efficacy of Evolvulus alsinoides (L.) L. on insulin and antioxidants activity in pancreas of streptozotocin induced diabetic rats.

AimDiabetes mellitus (DM), a leading non communicable disease with multiple etiologies is considered as third greatest cause of death in all over the world. During DM, persistent hyperglycemia causes an increased production of free radicals via auto oxidation of glucose and non-enzymatic protein glycation which may lead to disruption of cellular functions and oxidative damage to membranes. The present study was designed to investigate the therapeutic effect of Evolvulus alsinoides on antioxidant activity in pancreas of experimental diabetes.MethodsThe antioxidant activities were done by using standard protocols. For histopathological analysis, the pancreatic tissues of all experimental groups were fixed with 10% formalin for 24 hrs then the samples were stained with haemotoxylin-eosin for the microscopic observation.ResultsOral administration of plant extract for 45 days resulted in significant antioxidant activity, increases the insulin level and also inhibits lipid peroxidation in pancreas of streptozotocin induced diabetic rats. The histopathological studies showed the normal histology of pancreas after treatment with plant extract and glibenclamide. This study showed that the administration of Evolvulus alsinoides to streptozotocin induced diabetic rats improves the antioxidant activity and remodel the structure of pancreas due to the presence of secondary metabolites like phenols, flavonoids, alkaloids, steroids, terpenoids and glycosides in the ethanolic extract of plant material.ConclusionFrom the present study, it can be concluded that the plant extract effectively reduced the oxidative stress induced by streptozotocin and potentially increased the insulin level. Hence, it can be used in the management of diabetes mellitus.Electronic supplementary materialThe online version of this article (doi:10.1186/2251-6581-12-39) contains supplementary material, which is available to authorized users.

Mechanism and Stereoselectivity of Biologically Important Oxygenation Reactions of the 7-Dehydrocholesterol Radical

The mechanism of free radical oxygenation of 7-dehydrocholesterol (7-DHC), one of the biologically important sterols, is investigated by using density functional theory. The energetic origin of the product distribution and the stereoelectronic factors involved in various mechanistic pathways are delineated. The addition of triplet molecular oxygen to two types of conjugatively stabilized radicals, generated by the removal of the reactive allylic hydrogens from C9 or C14 positions, respectively denoted as H9 and H14 pathways, is studied. The distortion-interaction analysis of the C-O bond formation transition states suggests that the energetic preference toward the α prochiral face stems from reduced skeletal distortions of the cholesterol backbone as compared to that in the corresponding β prochiral face. This insight derived through a detailed quantitative analysis of the stereocontrolling transition states suggests that the commonly found interpretations solely based on steric interactions between the incoming oxygen and the protruding angular methyl groups (C10, C13 methyls) in the β face calls for adequate refinement. The relative energies of the transition states for molecular oxygen addition to C9, C5, and C14 (where spin densities are higher) and the ensuing products thereof are in agreement with the experimentally reported distribution of oxygenated 7-DHCs.