Presence Of Tert-butyl Hydroperoxide Research Articles

Synthesis, spectroscopic and electrochemical properties of ruthenium-2-(2′-hydroxyphenyl)-benzoxazole complexes. Crystal structure of [Ru(terpy)(HPB)Cl

Ruthenium(II) complexes utilizing both the 2,2′:6′,2″-terpyridine (terpy) and the Schiff base ligand, 2-(2′-hydroxyphenyl)-benzoxazole (HPB) were synthesized. The complex, Ru(terpy)(HPB)C1, was found to be formed in two isomeric forms, [Ru(terpy)(HPB)C1]·H 2O ( 1) and [Ru(terpy)(HPB)C1] ( 2). The isomers of the chloro complex result from the placement of the imine nitrogen or the phenolic oxygen of HPB trans to the chloro ligand. The structure of complex 2 has been determined by use of X-ray crystallography. The isomers exhibit similar electronic absorption patterns, but one isomer absorbs more into the visible region. Cyclic voltammetry of the complexes show a one electron Ru(III)/Ru(II) reversible couple, with complex 2 oxidized at a more positive potential than the complex 1. The aqua complexes, [Ru(terpy)(HPB)(H 2O)](PF 6) 2·2H 2O ( 3) and Ru(terpy)(HPB)(H 2O)]PF 6·H 2O ( 4) were also synthesized. In the presence of tert-butylhydroperoxide, the aqua complexes catalyzed the oxidation of diphenyl sulfide to diphenyl sulfoxide and phenyl methyl sulfide to phenyl methyl sulfoxide.

A supramolecular enzyme model catalyzing the central cleavage of carotenoids

Several bis-β-cyclodextrin porphyrins have been prepared as supramolecular receptors of carotenoids. The binding constants of carotenoids to receptors were determined by quenching the fluorescence of the porphyrins on hydrophobic binding of carotenoids within the cavities of cyclodextrins. Ka=8.3×106 M−1 was calculated for binding of β,β-carotene to bis-β-cyclodextrin Zn porphyrin. The corresponding Ru complex catalyzes the central cleavage of carotenoids in the presence of tert-butyl hydroperoxide in a biphasic system.

The development and application of ruthenium catalysed oxidations of a hydroxamic acid and in situ Diels–Alder trapping of the acyl nitroso derivative

Ruthenium( II) complexes can be used to oxidise N-Boc-hydroxylamine in the presence of tert-butyl hydroperoxide (TBHP) to the corresponding nitroso dienophile, which is trapped by cyclohexa-1,3-diene as the hetero-Diels–Alder adduct. Direct evidence has been obtained for the intervention of a triphenylphosphine oxide-stabilised ruthenium( IV) oxo-complex as the catalytically active species. Use of a chiral bidentate bis-phosphine derived ruthenium ligand (BINAP or PROPHOS) results in very low asymmetric induction (8 and 11%). Ruthenium( II) salen complexes also catalyse the oxidation of N-Boc-hydroxylamine in the presence of TBHP, to give the N-Boc-nitroso compound which can be efficiently trapped with a range of dienes. However, use of an enantiopure ruthenium salen complex does not produce asymmetric induction via the trapping of the intermediate acyl nitroso dienophile with cyclohexadiene, which strongly suggests that the intermediate dissociates readily from the chiral ruthenium complex involved in the oxidation step prior to Diels–Alder cycloaddition.

Oxidative ring cleavage of cyclic acetals with hypervalent tert-butylperoxy-lambda(3)-iodanes.

[reaction: see text] Exposure of cyclic acetals to 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one in the presence of tert-butyl hydroperoxide and potassium carbonate in benzene at room temperature results in oxidative ring cleavage to glycol monoesters via intermediate tert-butylperoxy ortho esters.

Synthesis and catalytic activity of Fe(III) anchored to a polystyrene–Schiff base support

Cross-linked styrene-divinylbenzene copolymer was functionalized into bidentate Schiff base bearing ligands. Immobilization of iron(III) on to the polymer matrix resulted in the synthesis of catalytically active metal complexes. These supported catalysts were found to be effective in the epoxidation of cis-cyclooctene and styrene in presence of tert-butylhydroperoxide under mild conditions. The influence of various reaction parameters on conversion and selectivity to products of epoxidation has been discussed.

4-Hydroxy-2-nonenal and Ethyl Linoleate Form N2,3-Ethenoguanine under Peroxidizing Conditions

In these studies, we demonstrate that N(2),3-ethenoguanine (N(2), 3-epsilonGua) is formed from lipid peroxidation as well as other oxidative reactions. Ethyl linoleate (EtLA) or 4-hydroxy-2-nonenal (HNE) was reacted with dGuo in the presence of tert-butyl hydroperoxide (t-BuOOH) for 72 h at 50 degrees C. The resulting N(2), 3-epsilonGua was characterized by liquid chromatography/electrospray mass spectroscopy and by gas chromatography/high-resolution mass spectral (GC/HRMS) analysis of its pentafluorobenzyl derivative following immunoaffinity chromatography purification. The amounts of N(2),3-epsilonGua formed were 825 +/- 20 and 1720 +/- 50 N(2), 3-epsilonGua adducts/10(6) normal dGuo bases for EtLA and HNE, respectively, corresponding to 38- and 82-fold increases in the amount of N(2),3-epsilonGua compared to controls containing only t-BuOOH. Controls containing t-BuOOH but no lipid resulted in a >1000-fold increase in the level of N(2),3-epsilonGua over dGuo that was not subjected to incubation. EtLA and HNE, in the presence of t-BuOOH, were reacted with calf thymus DNA at 37 degrees C for 89 h. The amounts of N(2),3-epsilonGua formed in intact ctDNA were 114 +/- 32 and 52.9 +/- 16.7 N(2),3-epsilonGua adducts/10(6) normal dGuo bases for EtLA and HNE, respectively. These compared to 2.02 +/- 0. 17 and 2.05 +/- 0.47 N(2),3-epsilonGua adducts/10(6) normal dGuo bases in control DNA incubated with t-BuOOH, but no lipid. [(13)C(18)]EtLA was reacted with dGuo to determine the extent of direct alkylation by lipid peroxidation byproducts. These reactions resulted in a 89-93% level of incorporation of the (13)C label into N(2),3-epsilonGua when EtLA and dGuo were in equimolar concentrations, when EtLA was in 10-fold molar excess, and when deoxyribose (thymidine) was in 10-fold molar excess. Similar reactions with ctDNA resulted in an 86% level of incorporation of the (13)C label. These data demonstrate that N(2),3-epsilonGua is formed from EtLA and HNE under peroxidizing conditions by direct alkylation. The data also suggest, however, that N(2),3-epsilonGua is also formed by an alternative mechanism that involves some other oxidative reaction which remains unclear.

Hydroperoxide specificity of plant and human tissue lipoxygenase: an in vitro evaluation using N-demethylation of phenothiazines

Since hydroperoxide specificity of lipoxygenase (LO) is poorly understood at present, we investigated the ability of cumene hydroperoxide (CHP) and tert-butyl hydroperoxide (TBHP) to support cooxidase activity of the enzyme toward the selected xenobiotics. Considering the fact that in the past, studies of xenobiotic N-demethylation have focused on heme-proteins such as P450 and peroxidases, in this study, we investigated the ability of non-heme iron proteins, namely soybean LO (SLO) and human term placental LO (HTPLO) to mediate N-demethylation of phenothiazines. In addition to being dependent on peroxide concentration, the reaction was dependent on enzyme concentration, substrate concentration, incubation time, and pH of the medium. Using Nash reagent to estimate formaldehyde production, the specific activity under optimal assay conditions for the SLO mediated N-demethylation of chlorpromazine (CPZ), a prototypic phenothiazine, in the presence of TBHP, was determined to be 117±12 nmol HCHO/min/mg protein, while that of HTPLO was 3.9±0.40 nmol HCHO/min/mg protein. Similar experiments in the presence of CHP yielded specific activities of 106±11 nmol HCHO/min/mg SLO, and 3.2±0.35 nmol HCHO/min/mg HTPLO. As expected, nordihydroguaiaretic acid and gossypol, the classical inhibitors of LOs, as well as antioxidants and free radical reducing agents, caused a marked reduction in the rate of formaldehyde production from CPZ by SLO in the reaction media fortified with either CHP or TBHP. Besides chlorpromazine, both SLO and HTPLO also mediated the N-demethylation of other phenothiazines in the presence of these organic hydroperoxides.

Synthesis and catalytic property of poly(styrene- co-divinylbenzene) supported ruthenium(III)-2-aminopyridyl complexes

Chloromethylated styrene-divinylbenzene copolymer beads with 8 and 14% cross-link were chemically modified by a reaction with 2-aminopyridine leading to the incorporation of nitrogen ligating sites on the surface of the polymer. These polymeric ligands, on treatment with a solution of ruthenium(III) chloride, gave the corresponding metal complex. The polymer supported Ru(III) complexes were characterized by elemental analysis, FT-IR, diffuse reflectance, SEM and DTA-TGA methods. The epoxidation of cis-cyclooctene, cyclohexene and styrene was investigated using the supported metal catalysts in presence of tert-butyl hydroperoxide as the terminal oxidant. Cis-cyclooctene gave the corresponding epoxide in a maximum yield of 51% whereas in case of styrene both styrene oxide and secondary oxidation product benzaldehyde were obtained in a combined yield of 95% under similar conditions. Surprisingly with cyclohexene as substrate the major product was 2-cyclohexene-1-one (64%) compared to the epoxide (2 %).

Asymmetric Epoxidation of alpha,beta-Unsaturated Ketones Catalyzed by Chiral Polybinaphthyl Zinc Complexes: Greatly Enhanced Enantioselectivity by a Cooperation of the Catalytic Sites in a Polymer Chain.

Polybinaphthyl zinc catalysts have been developed for the asymmetric epoxidation of alpha,beta-unsaturated ketones in the presence of tert-butyl hydroperoxide. Up to 81% ee has been achieved for the epoxidation of alpha,beta-unsaturated ketones containing beta-aliphatic substituents by using a binaphthyl polymer combined with diethylzinc. A very interesting positive cooperative effect of the catalytic sites in the polymer chain is observed which leads to greatly increased enantioselectivity over the corresponding monomer ligands.

Catalytic oxyfunctionalization of alkanes by manganese and ruthenium clusters

Di- and trinuclear clusters of manganese and ruthenium were used as catalysts in the oxidation of alkanes in the presence oftert-butyl hydroperoxide as oxidant. The investigations reveal marked differences in the reactivity of the manganese and ruthenium catalysts though structurally they have similar coordination environment. The probable mechanism of hydroxylation in these systems is discussed.

Iron(III) and copper(II) catalysed cyclohexane oxidation by molecular oxygen in the presence of tert-butyl hydroperoxide

In the presence of cyclohexane soluble iron and copper catalysts, tert-butyl hydroperoxide selectively oxidises cyclohexane to cyclohexanol and cyclohexanone (with cyclohexene for the copper catalysts). Under reflux for 24 h, the conversions are 4 to 5% (turnover numbers of 70 to 90) and the selectivities above 90%. Under 25 bar of oxygen at 70°C for 24 h, conversions with the iron catalysts are 9% (turnover numbers of up to 166) but the selectivities are below 80%, as large amounts of adipic acid are also formed. The copper catalysts are more selective under these conditions. Using Cu(tma) 2 the conversion is 11% (turnover number of 192) and the selectivity is 91%. Reactions in the presence of cyclohexanone show that the iron catalysts deactivate by complexation with the adipic acid formed by its over-oxidation. The copper catalysts rapidly produce cyclohexene at the beginning of the reactions; this is further oxidised to cyclohexen-3-one and cyclohexen-3-ol, thus reducing the catalyst activity for cyclohexane oxidation.

Dose-related inversion of cinnarizine and flunarizine effects on mitochondrial permeability transition.

We investigated the effects of cinnarizine and flunarizine on mitochondrial permeability transition, ATP synthesis, membrane potential and NAD(P)H oxidation. Both drugs were effective in inhibiting the mitochondrial permeability transition induced either by Ca2+ alone or in the presence of tert-butylhydroperoxide. This protective effect occurred at low concentrations (< 50 microM) of these drugs and was accompanied by the inhibition of NAD(P)H oxidation and the restoration of the mitochondrial membrane potential decreased by a high concentration of Ca2+ (25 microM). However, at higher concentrations (> 50 microM) of cinnarizine and flunarizine and in the absence of both tert-butylhydroperoxide and Ca2+, their effects on the mitochondria were reversed as follows: mitochondrial permeability transition was generated, mitochondrial NAD(P)H was oxidized and membrane potential collapsed. These deleterious effects were not antagonized by cyclosporine A, the most potent inhibitor of the mitochondrial permeability transition, but by 2,6-di-tert-butyl-4-methylphenol, a known antioxidant agent. This mitochondrial effect was neither accompanied by an increase in malondialdehyde production nor by an increase in H2O2 generation, which attested that the effect of both drugs was not due to an increase in reactive oxygen species production. The dual effects of both cinnarizine and flunarizine on mitochondrial functions is discussed with regard to both the protective effect afforded by these drugs against ischemia-reperfusion injury and their side effect observed in some therapeutic situations where an overdosage seems likely.

Thermic transition and glycolytic capacity as critical events in the survival of rat liver slices after overnight cold hypoxic preservation.

Cellular survival and hypoxia-reoxygenation injury in overnight cold-preserved liver slices (+/-20 h at 4 degrees C) were investigated. Increased cell death after overnight cold hypoxia depended more on temperature than on the reoxygenation process itself. Fructose (at 50 mM) added before the onset of hypoxia improved survival at the end of 20 h of cold hypoxia over Krebs- or glucose-treated slices. Such a protective effect by fructose was also seen during the normothermic (37 degrees C) reoxygenation of previously cold hypoxic-preserved slices, but only in the absence and not in the presence of tert-butyl hydroperoxide, a model compound widely used to induce an oxidative stress. The protection by fructose was equivalent to that observed when liver slices were incubated in the University of Wisconsin solution (UW). Finally, the morphological study of haematoxylin and eosin (H & E)-stained slices has shown cytoplasmic vacuoles during the reoxygenation step, which were more pronounced in UW-treated than in fructose-treated slices.

Thermic transition and glycolytic capacity as critical events in the survival of rat liver slices after overnight cold hypoxic preservation

Cellular survival and hypoxia–reoxygenation injury in overnight cold-preserved liver slices (±20 h at 4°C) were investigated. Increased cell death after overnight cold hypoxia depended more on temperature than on the reoxygenation process itself. Fructose (at 50 mM) added before the onset of hypoxia improved survival at the end of 20 h of cold hypoxia over Krebs- or glucose-treated slices. Such a protective effect by fructose was also seen during the normothermic (37°C) reoxygenation of previously cold hypoxic-preserved slices, but only in the absence and not in the presence of tert-butyl hydroperoxide, a model compound widely used to induce an oxidative stress. The protection by fructose was equivalent to that observed when liver slices were incubated in the University of Wisconsin solution (UW). Finally, the morphological study of haematoxylin and eosin (H & E)-stained slices has shown cytoplasmic vacuoles during the reoxygenation step, which were more pronounced in UW-treated than in fructose-treated slices. © 1998 John Wiley & Sons, Ltd.

Polymer supported Ru(III) complexes, synthesis and catalytic activity

Crosslinked chloromethylated polystyrene-divinylbenzene polymers were chemically modified into Schiff base bearing ligands. Catalytically active metal supported polymers containing Ru(III) moieties were synthesized from these ligands for use in the selective epoxidation of olefins in presence of tert-butyl hydroperoxide as oxidant. These ruthenium anchored polymers were characterized by spectral and thermoanalytical methods. Catalyst morphology and physicochemical properties such as surface area, bulk density and swelling behaviour in different solvents were studied. The effects of reaction parameters such as catalyst concentration, temperature, time and solvent on conversion and selectively in the epoxidation of cis-cyclooctene and styrene are discussed.

Nanoscale redox catalysts: Cr- and Cr,Al-pillared layer clays: Characterization and catalytic activity

Via the co-hydrolysis of CrCl 3 and AlCl 3 in the presence of swollen Na-montmorillonite, pillared layer clays were prepared. The location of chromium in the pillars and in the primary pillaring agent, the Al 13-Keggin ion, was investigated by various methods (mid and far IR and 27Al NMR spectroscopies). We found that isomorphous substitution of chromium for aluminium did not occur, rather co-hydrolysis and co-pillaring took place. Upon heat treatment the loss of outer-sphere water and dehydroxylation at higher temperatures resulted in the formation of bulky alumina pillars decorated with chromia species. The resulting material was used in the oxidation of 1-phenyl-1-propanol in the presence of tert-butylhydroperoxide as co-oxidant.

Influence of the Redox State of Pyridine Nucleotides on Mitochondrial Sulfhydryl Groups and Permeability Transition

This work addresses a correlation between the redox state of pyridine nucleotides and that of sulfhydryl groups of the mitochondrial membranes. Several major observations emerge: (1) Conditions leading to an oxidation of the pyridine nucleotides such as incubation withtert-butyl hydroperoxide or acetoacetate determine a decrease of total mitochondrial sulfhydryl groups. Glutathione does not follow the same pattern since it decreases in the presence oftert-butyl hydroperoxide but not in the presence of acetoacetate. In addition, only in the presence oftert-butyl hydroperoxide is the decrease of sulfhydryl groups concomitant with a membrane protein polymerization, observed by polyacrylamide gel electrophoresis. (2) Under all conditions tested, the oxidation of sulfhydryl groups is further stimulated by the presence of calcium and phosphate ions. (3) Respiratory substrates, which prevent the swelling of mitochondria, also partially prevent the decrease of sulfhydryl groups.

The Calcium Sensor Ruthenium Red Can Act as a Fenton-Type Reagent

Ruthenium red (RR), an ammoniated form oftris-rutheniumIII,IV,IIIoxychloride, has been widely used in the micromolar range as a strong and specific inhibitor ofin vitroandin vivoCa2+-mediated biochemical processes without regard for its redox properties. We show here that in the presence oftert-butyl hydroperoxide (TBHP) and an electron source, either succinate-energized rat liver mitochondria or ascorbate, RR amplifies the generation of methyl radicals. The EPR spin trapping signal of the 5,5-dimethyl-1-pyrroline-N-oxide/methyl radical (DMPO/•CH3) adduct obtained from incubations of TBHP (1.5 mM) and mitochondria (5 mg protein/ml) in an adequate medium increases upon addition of RR in a concentration-dependent fashion: sixfold at 10 μMRR. Respiring mitochondria can be replaced by ascorbate (1 mM), the characteristic EPR signal of the ascorbyl radical also being observed (aH= 0.18 mT). Spectrophotometric, cyclic voltammetric and spectroelectrochemical studies unequivocally show oxidation of RRIII,IV,III(λmax= 538 nm) to the rutheniumIV,III,IVspecies (“ruthenium brown,” RB; λmax= 464 nm) by TBHP, followed by its one-electron back reduction to RR by the respiratory chain or ascorbate. The calcium chelator EGTA (1 mM) strongly binds and stabilizes the RR form, slowing down its recycling by TBHP and either ascorbate or the mitochondrial electron chain. These data clearly show that RuIIIin the RR complex can reduce TBHP via a Fenton-type reaction and thus must be considered when RR is used as a tool to study biological processes simultaneously involving Ca2+ions and peroxides.

Apoptosis Induced by Transforming Growth Factor-β in Fetal Hepatocyte Primary Cultures: INVOLVEMENT OF REACTIVE OXYGEN INTERMEDIATES

Transforming growth factor-beta (TGF-beta), a growth regulator of fetal hepatocytes in primary culture, also regulates death of these cells. Dose-response analysis showed that the TGF-beta concentration needed to induce hepatocyte death (2.5 ng/ml) was 5 times that needed to inhibit growth in these cells (0.5 ng/ml). In response to TGF-beta, hepatocytes induced DNA fragmentation and the appearance of nuclei with a DNA content lower than 2C (diploid content), typical of a programmed cell death model. TGF-beta-induced apoptosis in fetal hepatocytes was preceded by an induction of reactive oxygen species production and a decrease in the glutathione intracellular content, indicating that this factor induces oxidative stress in fetal hepatocytes. Studies performed to analyze levels of c-fos mRNA, a gene whose expression is modulated by redox state, demonstrated that only high, apoptotic concentrations of TGF-beta (2.5 ng/ml) produced an increase in the mRNA levels of this gene, the level of induction being similar to that found when cells were incubated in the presence of tert-butyl hydroperoxide. Gel mobility shift assays showed that the c-fos-induced expression was coincident with an increase in AP-1 activity. Finally, cell death induced by TGF-beta in fetal hepatocytes was partially blocked by radical scavengers, which decreased the percentage of apoptotic cells, whereas these agents did not modify the growth-inhibitory effect elicited by TGF-beta in these cells. In summary, the results presented in this paper provide evidence for the involvement of an oxidative process in the apoptosis elicited by TGF-beta in fetal hepatocytes.

Oxyfunctionalization of cyclohexane catalyzed by oxo-bridged manganese Schiff base complexes

Oxo-bridged polynuclear manganese Schiff base complexes catalyzed the oxidation of cyclohexane to cyclohexanol and cyclohexanone In the presence of tert-butyl hydroperoxide or hydrogen peroxide.