Peroxide Intermediates Research Articles

Sterol carrier protein-2 (SCP-2) involvement in cholesterol hydroperoxide cytotoxicity as revealed by SCP-2 inhibitor effects

Sterol carrier protein-2 (SCP-2) plays an important role in cholesterol trafficking and metabolism in mammalian cells. The purpose of this study was to determine whether SCP-2, under oxidative stress conditions, might also traffic hydroperoxides of cholesterol, thereby disseminating their cytotoxic effects. Two inhibitors, SCPI-1 and SCPI-3, known to block cholesterol binding by an insect SCP-2, were used to investigate this. A mouse fibroblast transfectant clone (SC2F) overexpressing SCP-2 was found to be substantially more sensitive to apoptotic killing induced by liposomal 7α-hydroperoxycholesterol (7α-OOH) than a wild-type control. 7α-OOH uptake by SC2F cells and resulting apoptosis were both inhibited by SCPI-1 or SCPI-3 at a subtoxic concentration. Preceding cell death, reactive oxidant accumulation and loss of mitochondrial membrane potential were also strongly inhibited. Similar SCPI protection against 7α-OOH was observed with two other types of SCP-2-expressing mammalian cells. In striking contrast, neither inhibitor had any effect on H(2)O(2)-induced cell killing. To learn whether 7α-OOH cytotoxicity is due to uptake/transport by SCP-2, we used a fluorescence-based competitive binding assay involving recombinant SCP-2, NBD-cholesterol, and SCPI-1/SCPI-3 or 7α-OOH. The results clearly showed that 7α-OOH binds to SCP-2 in SCPI-inhibitable fashion. Our findings suggest that cellular SCP-2 not only binds and translocates cholesterol but also cholesterol hydroperoxides, thus expanding their redox toxicity and signaling ranges under oxidative stress conditions.

Reactivity of the Gold/Water Interface During Selective Oxidation Catalysis

The selective oxidation of alcohols in aqueous phase over supported metal catalysts is facilitated by high-pH conditions. We have studied the mechanism of ethanol and glycerol oxidation to acids over various supported gold and platinum catalysts. Labeling experiments with (18)O(2) and H(2)(18)O demonstrate that oxygen atoms originating from hydroxide ions instead of molecular oxygen are incorporated into the alcohol during the oxidation reaction. Density functional theory calculations suggest that the reaction path involves both solution-mediated and metal-catalyzed elementary steps. Molecular oxygen is proposed to participate in the catalytic cycle not by dissociation to atomic oxygen but by regenerating hydroxide ions formed via the catalytic decomposition of a peroxide intermediate.

ChemInform Abstract: Studies Towards the Synthesis of Aplykurodins - Synthesis of 17,18-Dihydro-3,9-di-epi-aplykurodinone B.

An approach to the synthesis of aplykurodins, ichthyotoxic marine lactones, is presented. The carbon framework was derived from vitamin D3 by conversion of the readily accessible allyl alcohol 13 to the protected Grundmann's hydroxy ketone 22 and subsequent introduction of the C2 side chain through a Pd0-promoted coupling. Highly stereoselective hetero Diels-Alder reaction with O21 produced the key intermediate peroxide 25. Functional group transformations, coupled with a series of chemo- and stereoselective reactions, finally resulted in the synthesis of the unnatural analogue 17,18-dihydro-3,9-di-epi-aplykurodinone B (6).

Systematic Perturbation of the Trinuclear Copper Cluster in the Multicopper Oxidases: The Role of Active Site Asymmetry in Its Reduction of O2 to H2O

The multicopper oxidase Fet3p catalyzes the four-electron reduction of dioxygen to water, coupled to the one-electron oxidation of four equivalents of substrate. To carry out this process, the enzyme utilizes four Cu atoms: a type 1, a type 2, and a coupled binuclear, type 3 site. Substrates are oxidized at the T1 Cu, which rapidly transfers electrons, 13 A away, to a trinuclear copper cluster composed of the T2 and T3 sites, where dioxygen is reduced to water in two sequential 2e(-) steps. This study focuses on two variants of Fet3p, H126Q and H483Q, that perturb the two T3 Cu's, T3alpha and T3beta, respectively. The variants have been isolated in both holo and type 1 depleted (T1D) forms, T1DT3alphaQ and T1DT3betaQ, and their trinuclear copper clusters have been characterized in their oxidized and reduced states. While the variants are only mildly perturbed relative to T1D in the resting oxidized state, in contrast to T1D they are both found to have lost a ligand in their reduced states. Importantly, T1DT3alphaQ reacts with O(2), but T1DT3betaQ does not. Thus loss of a ligand at T3beta, but not at T3alpha, turns off O(2) reactivity, indicating that T3beta and T2 are required for the 2e(-) reduction of O(2) to form the peroxide intermediate (PI), whereas T3alpha remains reduced. This is supported by the spectroscopic features of PI in T1DT3alphaQ, which are identical to T1D PI. This selective redox activity of one edge of the trinuclear cluster demonstrates its asymmetry in O(2) reactivity. The structural origin of this asymmetry between the T3alpha and T3beta is discussed, as is its contribution to reactivity.

Isolation and Characterization of Cetirizine Degradation Product: Mechanism of Cetirizine Oxidation

The goal of the study was to isolate and analyze a cetirizine degradation product, formed within a PEG-containing formulation and to elucidate the mechanism of oxidation of cetirizine. Cetirizine, formulated in PEG-containing matrix, was subjected to forced degradation conditions in the pH range from 3 to 10, and the product was analyzed by HPLC and LC-MS/MS. Additionally, pure cetirizine was subjected to selective oxidization by hydrogen peroxide and sodium percarbonate. The reaction mixture was purified, and the isolated material was analyzed by (1)H NMR. Oxidation process was investigated in order to model the degradation of cetirizine in PEG-containing formulation. Site of oxidation is proposed based on correlation of the results of forced degradation with ionization scheme of cetirizine. The finding was verified by spiking of cetirizine degradation sample with cetirizine N-oxide reference standard. Degradation of cetirizine in polyethylene glycol arose from the reaction between the drug and the reactive peroxide intermediates such as peroxyl radicals formed through oxidation of PEG. Selective oxidation of cetirizine and isolation/characterization of the oxidation product allowed the identification of the oxidation product as cetirizine N-oxide. The mechanism of oxidation is proposed.

Ion Release Kinetics and Particle Persistence in Aqueous Nano-Silver Colloids

Many important aspects of nanosilver behavior are influenced by the ionic activity associated with the particle suspension, including antibacterial potency, eukaryotic toxicity, environmental release, and particle persistence.The present study synthesizes pure, ion-free, citrate-stabilized nanosilver (nAg) colloids as model systems, and measures their time-dependent release of dissolved silver using centrifugal ultrafiltration and atomic absorption spectroscopy. Ion release is shown to be a cooperative oxidation process requiring both dissolved dioxygen and protons. It produces peroxide intermediates, and proceeds to complete reactive dissolution under some conditions. Ion release rates increase with temperature in the range 0-37 °C, and decrease with increasing pH or addition of humic or fulvic acids. Sea salts have only a minor effect on dissolved silver release. Silver nanoparticle surfaces can adsorb Ag(+), so even simple colloids contain three forms of silver: Ag(0) solids, free Ag(+) or its complexes, and surface-adsorbed Ag(+). Both thermodynamic analysis and kinetic measurements indicate that Ag(0) nanoparticles will not be persistent in realistic environmental compartments containing dissolved oxygen. An empirical kinetic law is proposed that reproduces the observed effects of dissolution time, pH, humic/fulvic acid content, and temperature observed here in the low range of nanosilver concentration most relevant for the environment.

Mechanism of Water Oxidation by Single-Site Ruthenium Complex Catalysts

The mechanism of Ce(IV) water oxidation catalyzed by [Ru(tpy)(bpm)(OH(2))](2+) (tpy = 2,2':6',2''-terpyridine; bpm = 2,2'-bipyrimidine) and related single-site catalysts has been determined by a combination of mixing and stopped-flow experiments with spectrophotometric monitoring. The mechanism features O---O coupling by water attack on Ru(V)=O(3+) and three peroxidic intermediates that have been characterized by a combination of spectroscopy and DFT calculations.

Facetted platinum electrocatalysts for electrochemical energy converters

The preparation and characterisation of Pt nanoparticles electrodeposited on carbon substrates by pulsating electrolysis are presented. The characterisation studies of metal electrodeposits by using SEM, TEM, XRD and cyclic voltammetry revealed the presence of facetted Pt nanoparticles having a predominant (111) preferential crystal orientation. The amount of electrodeposited Pt was determined by means of a spectrophotometric technique. An improvement in performance of the hydrogen/oxygen PEM fuel cell with (111)-type Pt nanoparticles incorporated in the cathode was observed, which was assigned to the decrease of the blocking effect of the cathode electrode surface by intermediate peroxide species produced during the overall oxygen electroreduction process.

Synthesis and antimalarial activities of optically active labdane-type diterpenes

An efficient method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8 is described. We prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9, and synthetic hydroxybutenolides 6 and 7 via a furan photosensitised oxygenation reaction of labdafuran (14). Compounds 5, 6, 7 and 9 were evaluated as inhibitors of the β-haematin formation and globin proteolysis, and then were assayed in a malarial murine model. Compound 9 was the most promising compound, showing a positive correlation between in vitro and in vivo activities.

Multi-walled carbon nanotube-supported tungsten oxide-containing multifunctional hybrid electrocatalytic system for oxygen reduction in acid medium

Combination of multi-walled carbon nanotubes, cobalt porphyrin and tungsten oxide in the film (deposited onto glassy carbon electrode substrate) produces an electrocatalytic system capable of effective reduction of oxygen in such acid medium as 0.5 mol dm −3 H 2SO 4. Co-existence of cobalt porphyrin and tungsten oxide, together with dispersed carbon nanotubes, leads to the enhancement effect evident from some positive shift in the oxygen reduction voltammetric potential and the significant increase of voltammetric currents (relative to those characteristic of the system free of carbon nanotubes and WO 3). The multi-component electrocatalytic film has also exhibited relatively higher activity towards reduction of hydrogen peroxide. It is reasonable to expect that the reduction of oxygen is initiated at the cobalt porphyrin redox centers, and the undesirable hydrogen peroxide intermediate is further reduced at the tungsten oxide support. An important function of carbon nanotubes is to improve transport of electrons within the electrocatalytic multi-component film.

Development of Bifunctional Carbon Nanotube-Supported Co-Porphyrin Electrocatalytic System for Oxygen Reduction

Combination of multiwalled carbon nanotubes, cobalt porphyrin and tungsten oxide produces a multifunctional electrocatalytic system capable of the effective reduction of oxygen in acid medium. The resulting inks have been utilized during sequential deposition of components. Co-existence of Co-porphyrin, tungsten oxide together with dispersed carbon nanotubes leads to synergistic effect that is evident from positive shift of the oxygen reduction potentials, significant increase of voltammetric currents (relative to those observed at a system not containing carbon nanotube-supported tungsten oxide) and decrease of hydrogen peroxide produced during oxygen reduction. It is reasonable to expect that the reduction of oxygen is initiated at metalloporphyrin redox centers, and the undesirable hydrogen peroxide intermediate is further reduced at partially reduced tungsten oxide. In addition to the methanol tolerance other important issue is the tolerance of the proposed system to ethanol that may appear due to crossover in the cathode compartments of ethanol fuel cells.

Benzylamine-Free, Heavy-Metal-Free Synthesis of CL-20 via Hexa(1-propenyl)hexaazaisowurtzitane

Base-catalyzed isomerization of recently reported hexaallylhexaazaisowurtzitane produced a new derivative, hexa(1-propenyl)hexaazaisowurtzitane (HPIW). Photooxygenation of this intermediate by singlet oxygen oxidized most of the 1-propenyl substituents to formyl substituents. The course of this reaction of singlet oxygen with HPIW involves peroxide intermediates, which may include relatively stable macrocyclic (tetroxocane) derivatives. The resulting nitrolyzable polyformylhexaazaisowurtzitane was found to be a promisingly efficient new precursor to CL-20 (in a single preliminary experiment without any process development). The new intermediate HPIW also underwent direct nitrolysis to form CL-20, though not as efficiently as its photooxygenation product did.

Photoelectrochemical Properties of BiVO4 Film Electrode in Alkaline Solution

Abstract A pressed BiVO4 film electrode with excellent performance has been prepared by a doctor blade method. The photoelectrochemical properties of the electrode in 0.1 mol/L NaOH have been studied. The results showed that the photocurrent and stability were better than those in the Na2SO4 electrolyte. Combined with the cyclic voltammograms for the intermediate analysis, the results indicated that the water photooxidation is a nucleophilic attack process involving four holes. The nucleophilic attack reaction is favorable in higher- pH alkaline solution, and the accumulation of peroxide intermediates is decreased. Moreover, when a higher bias is applied in an alkaline solution, the water photooxidation mechanism is more complex, and some bismuth intermediates are probably involved in the process.

Kinetic Study of Advanced Oxidation of Eosin Dye by Fenton's Reagent

An advanced oxidation study using Fenton's reagent, i.e., ferrous sulfate and hydrogen peroxide was carried out for studying oxidation of eosin dye. Effects of concentration of various reagents on the degradation of dye were explored during an advanced oxidation process. It was found that ferrous concentration plays a major role in dye decomposition. Rate of dye decomposition is faster with an increase in ferrous sulfate concentration compared to the increase in hydrogen peroxide concentration. A detailed kinetic model was proposed. Profiles for eosin, hydrogen peroxide and various intermediates were also generated. The rate constant of the reaction of eosin with a hydroxyl radical was found to be of the order of 109 l/mol.s.

Photooxidation of metal-bound thiolates: reactivity of sulfur containing peroxidic intermediates

A variety of reactions of singlet oxygen with metal-bound thiolates are described, and contrasted with the photooxidation of organic sulfides. Superficially, these two processes appear to involve similar mechanisms, but there are important differences: unlike the photooxidation of organic sulfides, the rate of the initial reaction of metal-thiolates with singlet oxygen (k t) appears to be affected by protic solvents and acids. The nucleophilicity of the thiolate moiety is reduced by addition of acids or in protic solvents, leading to significantly lower k t values. The primary intermediate in the photooxidation of organic sulfides is a nucleophilic persulfoxide, which can be stabilized by protic solvents or by addition of acid. However, the primary intermediate in the photooxidation of metal thiolates cannot be trapped with phosphite, suggesting that it may be less nucleophilic than its organic counterpart. Support for this hypothesis is also derived from the rather modest (compared with organic sulfides) acceleration of the rate of product formation by addition of acid.

Comparative histochemical analyses of oxidative burst and cell wall reinforcement in compatible and incompatible melon–powdery mildew ( Podosphaera fusca) interactions

The spatial-temporal expression patterns of oxidative burst and cell wall reinforcement were analyzed in leaves of resistant and susceptible melon (Cucumis melo L.) cultivars in response to Podosphaera fusca (Fr.) Braun & Shishkoff, the main causal agent of powdery mildew in cucurbits. Extensive development of powdery mildew mycelia and a progressive increase in haustorial count were recorded in the susceptible cultivar after 4d, while in the resistant cultivar powdery mildew failed to grow and small brownish and necrotic leaf areas were frequently observed. Rapid generation of the reactive oxygen intermediates hydrogen peroxide and superoxide radicals 4h after pathogen challenge, but before the fungal haustoria formation, stood upstream in the cascade of events induced during these interactions. This oxidative burst was followed by the accumulation of strengthening polymers of callose and lignin at the cell wall of attacked resistant plant cells. Interestingly, the transcriptional levels of phenylalanine ammonia-lyase (PAL), an important enzyme for phenylpropanoid metabolism, did not significantly change throughout the experiments. Although these physiological changes were observed in both cultivars, their faster kinetics and amplitude in the resistant line compared to the susceptible cultivar governed the differential visual response of these cultivars against P. fusca. These findings, along with data obtained in previous studies, have provided the bases for an integrated model in which the spatial-temporal response patterns of these resistance mechanisms have been arranged, which may ultimately lead to successful protection of melon plants against P. fusca.

Bifunctional Bioelectrocatalytic Systems for Oxygen Reduction

Combination of polyoxometallate-modified multi-walled carbon nanotubes, cobalt porphyrin, and peroxidase (horseradish, cabbage) enzyme within the film (deposited on glassy carbon) produces a bio-electrocatalytic system capable of effective reduction of oxygen in neutral media such as 0.1 mol dm-3 KCl and 0.1 mol dm-3 KCl + 0.01 citrate buffer (pH=6). An important function of carbon nanotubes is to improve transport of electrons within the film. Co-deposition of the peroxidase enzyme together with the cobalt porphyrin catalytic centers leads to bifunctional synergistic effect that is evident from sizeable positive shift of the oxygen reduction potentials and significant increase of voltammetric currents. The bio- electrocatalytic system also exhibits relatively much higher reductive activity towards hydrogen peroxide. It is reasonable to expect that the reduction of oxygen is initiated at cobalt porphyrin redox centers, and the undesirable hydro gen peroxide intermediate is further reduced at the horseradish or cabbage peroxidase enzymatic sites.

Facile Access to Labdane‐Type Diterpenes: Synthesis of Coronarin C, Zerumin B, Labda‐8(17), 13(14)‐Dien‐15,16‐olide and Derivatives from (+)‐Manool.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Enhancement of bio-electrocatalytic oxygen reduction at the composite film of cobalt porphyrin immobilized within the carbon nanotube-supported peroxidase enzyme

Combination of multi-walled carbon nanotubes, cobalt porphyrin, and peroxidase (horseradish, cabbage) enzyme in the film (deposited onto glassy carbon electrode substrate) produces a bio-electrocatalytic system capable of effective reduction of oxygen in such neutral media as 0.1 mol dm −3 KCl and 0.1 mol dm −3 KCl + 0.01 citrate buffer (pH 6). Carbon nanotubes have been modified with ultra-thin layers of 4-(pyrrole-1-yl) benzoic acid, or phosphododecamolybdate, to form stable colloidal suspensions of carbon nanostructures. The resulting inks have been utilized during sequential deposition of components. Co-existence of cobalt porphyrin, peroxidase enzyme together with dispersed carbon nanotubes leads to synergistic effect that is evident from some positive shift of the oxygen reduction voltammetric potentials (more than 50 mV in citrate buffer) and significant (ca. twice) increase of voltammetric currents (relative to those of the enzyme-free system). The multi-component bio-electrocatalytic film has also exhibited relatively higher activity towards reduction of hydrogen peroxide. It is reasonable to expect that the reduction of oxygen is initiated at cobalt porphyrin redox centers, and the undesirable hydrogen peroxide intermediate is further reduced at the horseradish or cabbage peroxidase enzymatic sites. An important function of carbon nanotubes is to improve transport of electrons within the bio-electrocatalytic multi-component film.

NF‐kB and caspases are involved in the hyaluronan and chondroitin‐4‐sulphate‐exerted antioxidant effect in fibroblast cultures exposed to oxidative stress

Oxidative stress, inflammation and apoptosis play a critical role in the onset and progression of cellular damage. It was previously reported that hyaluronan (HA) and chondroitin-4-sulphate (C4S) were able to protect human skin fibroblasts from oxidative stress. This antioxidant activity is due to the chelation of transition metal ions. Nuclear factor kB (NF-kB), complexed with the inhibitory protein IkB alpha, is an ubiquitous response transcription factor involved in inflammatory reactions and acts by inducing cytokine expression, chemokines and cell adhesion molecules. Caspases are specific proteases responsible for the regulation and the execution of apoptotic cell death. The damage caused by free radicals may be amplified greatly by the activation of these factors. The study investigated whether the ability of these glycosaminoglycans (GAGs) to reduce oxidative damage in fibroblast cultures involves NF-kB and caspases modulation. The treatment of fibroblasts with both HA and C4S limited the cell damage induced by FeSO(4) plus ascorbate. An interesting aspect of this treatment was that these GAGs significantly inhibited NF-kB DNA binding, as confirmed by the normalization of IkB alpha protein, and reduced caspase activation at both mRNA and protein level. A possible explanation for these results, since lipid peroxidation intermediates may induce NF-kB and caspase activation, is that HA and C4S indirectly blocked NF-kB DNA binding and apoptosis by inhibiting reactive oxygen species (ROS) production. These data suggest that, during oxidative stress, HA and C4S may reduce cell damage by inhibiting NF-kB and apoptosis activation as well as protecting cells from free radical attack. According to these finding the use of HA and C4S could be positive both as tool to clarify the exact mechanism of GAGs/ROS interaction, and also as drug therapy to reduce oxidative stress during inflammation.