Organoselenium Chemistry. Preparation of Allyl and Homoallyl Amines by Aminomethylation of Phenylseleno-Substituted Allyl Tin Reagents

Metalation of methallyl phenyl selenide, allyl phenyl selenide, and methallyl phenyl sulfide followed by tri-n-butylstannylation gave exclusively the γ-stannylated sulfide or selenide (e.g., 1-phenylseleno-2-methyl-3-tri-n-butylstannyl-1-propene ( 5 )). Compound 5 reacts with a series of immonium electrophiles to give products of aminomethylation α- to selenium. Electrophiles have included N-(bromomethyl)phthalimide/ZnBr₂, Eschenmoser salt (dimethylmethyleneammonium iodide), and Mannich reagents generated in situ from diethylamine, piperidine, isopropyl sarcosinate and benzylmethylamine. The selenide from the last of these amines (N, 3-dimethyl-N-benzyl-2-phenylseleno-3-butenamine, 10 ) has been subjected to further transformations as follows: (1) treatment of 10 with trimethylstannyllithium results in replacement of phenylseleno by stannyl; this allyltin ( 11 ) can then again be aminomethylated giving compound 12 or 13 ; (2) oxidation of 10 gives amino alcohol 14 by [2, 3] sigmatropic rearrangement of the allyl selenoxide; (3) photolysis of 10 results in 1,3-rearrangement of the phenylseleno group; oxidative rearrangement of this allyl selenide gives amino alcohol 16 . The phthalimidomethylation product ( 6 ) is converted to a precursor for the side chain of the cytokinin zeatin by oxidation and [2, 3] sigmatropic rearrangement.     

Reversibly Redox‐Switchable Anionic Surfactant Contains Two Selenium Atoms

To better control the interfacial activities of selenium‐containing surfactants, a redox‐switchable anionic surfactant containing 2 selenium atoms, namely sodium 3‐((3‐(benzylselanyl)propyl)selanyl)propyl sulfate (SBSe₂S), has been designed and synthesized. Upon oxidation by H₂O₂, the 2 divalent selenide groups in the hydrophobic tail of SBSe₂S are converted into the corresponding selenoxides. The initial hydrophobic tail of SBSe₂S gets separated into 3 segments by 2 hydrophilic selenoxide groups, destroying the bola‐type structure. The interfacial activities of SBSe₂S in aqueous solution could thereby be switched off to a greater degree than in the case of its counterparts containing only a single selenium atom. After reduction with Na₂SO₃, the 2 selenoxide groups in SBSe₂S‐Ox are restored to the initial selenide. Consequently, the interfacial activities of SBSe₂S could be reversibly switched by alternate addition of H₂O₂ and Na₂SO₃, without obvious deterioration over 5 cycles.     

Synthesis and Characterization of Cadmium Selenide (CdSe) Nanoparticles Using Trigonal Selenium (t-Se) Nanorods as Selenium Source

Cadmium selenide (CdSe) nanoparticles were synthesized through colloidal method in aqueous medium using the reaction intermediates selenium nanorods as selenium source. Trigonal selenium nanorods (t-Se) were synthesized in water by the reduction method in the presence of sodium borohydride at 60?°C using sodium selenite (Na₂SeO₃) as selenium source. These selenium nanorods were further utilized to synthesis cadmium selenide nanoparticles at 100?°C in water. The synthesized nanorods and nanoparticles were characterized using XRD, SEM, TEM and XPS analysis. X-ray diffraction (XRD) analysis shown that the nanorods possess trigonal phase while the nanoparticles possess a cubic zinc blende structure. Scanning electron microscope (SEM) analysis of the prepared hexagonal shaped nanorods reveals the diameter of the nanorods are about 150 nm. Transmission electron microscopy (TEM) analysis shows the size of the synthesized CdSe nanoparticles are about 4–8 nm. X-ray photoelectron spectroscopy (XPS) analysis illustrates the presence of respective elements Cd, Se with its corresponding oxidation states. The activity of nano selenium rods in aqueous solution during the conversion of cadmium selenide nanoparticles was discussed.     

Dual Activities of Oxidation and Oxidative Decarboxylation by Flavoenzymes

Specific flavoenzyme oxidases catalyze oxidative decarboxylation in addition to their classical oxidation reactions in the same active sites. The mechanisms underlying oxidative decarboxylation by these enzymes and how they control their two activities are not clearly known. This article reviews the current state of knowledge of four enzymes from the l -amino acid oxidase and l -hydroxy acid oxidase families, including l -tryptophan 2-monooxygenase, l -phenylalanine 2-oxidase and l -lysine oxidase/monooxygenase and lactate monooxygenase which catalyze substrate oxidation and oxidative decarboxylation. Apart from specific interactions to allow substrate oxidation by the flavin cofactor, specific binding of oxidized product in the active sites appears to be important for enabling subsequent decarboxylation by these enzymes. Based on recent findings of l -lysine oxidase/monooxygenase, we propose that nucleophilic attack of H₂O₂ on the imino acid product is the mechanism enabling oxidative decarboxylation.     

Selective oxidation of H<Subscript>2</Subscript>S to ammonium thiosulfate and elemental sulfur using mixtures of V-Bi-O and Sb<Subscript>2</Subscript>O<Subscript>4</Subscript>

The selective oxidation of hydrogen sulfide in the presence of excess water and ammonia was investigated by using vanadium-bismuth based mixed oxide catalysts. Synergistic effect on catalytic activity was observed for the mechanical mixtures of V-Bi-O and Sb₂O₄. Temperature programmed oxidation (TPO), X-ray photoelectron spectroscopy (XPS), and two separated bed reactivity test results supported the role of Sb₂O₄ for reoxidizing the reduced V-Bi-O during the reaction. This paper is dedicated to Professor Hyun-Ku Rhee on the occasion of his retirement from Seoul National University.     

A Caged,Destabilized, Free Radical Intermediate in the Q‐Cycle

The Rieske/cytochrome b complexes, also known as cytochrome bc complexes, catalyze a unique oxidant‐induced reduction reaction at their quinol oxidase (Q_o) sites, in which substrate hydroquinone reduces two distinct electron transfer chains, one through a series of high‐potential electron carriers, the second through low‐potential cytochrome b. This reaction is a critical step in energy storage by the Q‐cycle. The semiquinone intermediate in this reaction can reduce O₂ to produce deleterious superoxide. It is yet unknown how the enzyme controls this reaction, though numerous models have been proposed. In previous work, we trapped a Q‐cycle semiquinone anion intermediate, termed SQ_o, in bacterial cytochrome bc₁ by rapid freeze‐quenching. In this work, we apply pulsed‐EPR techniques to determine the location and properties of SQ_o in the mitochondrial complex. In contrast to semiquinone intermediates in other enzymes, SQ_o is not thermodynamically stabilized, and can even be destabilized with respect to solution. It is trapped in Q_o at a site that is distinct from previously described inhibitor‐binding sites, yet sufficiently close to cytochrome b_L to allow rapid electron transfer. The binding site and EPR analyses show that SQ_o is not stabilized by hydrogen bonds to proteins. The formation of SQ_o involves “stripping” of both substrate ‐OH protons during the initial oxidation step, as well as conformational changes of the semiquinone and Q_o proteins. The resulting charged radical is kinetically trapped, rather than thermodynamically stabilized (as in most enzymatic semiquinone species), conserving redox energy to drive electron transfer to cytochrome b_L while minimizing certain Q‐cycle bypass reactions, including oxidation of prereduced cytochrome b and reduction of O₂.     

Insulin-Dependent H2O2 Production Is Higher in Muscle Fibers of Mice Fed with a High-Fat Diet

Insulin resistance is defined as a reduced ability of insulin to stimulate glucose utilization. C57BL/6 mice fed with a high-fat diet (HFD) are a model of insulin resistance. In skeletal muscle, hydrogen peroxide (H₂O₂) produced by NADPH oxidase 2 (NOX2) is involved in signaling pathways triggered by insulin. We evaluated oxidative status in skeletal muscle fibers from insulin-resistant and control mice by determining H₂O₂ generation (HyPer probe), reduced-to-oxidized glutathione ratio and NOX2 expression. After eight weeks of HFD, insulin-dependent glucose uptake was impaired in skeletal muscle fibers when compared with control muscle fibers. Insulin-resistant mice showed increased insulin-stimulated H₂O₂ release and decreased reduced-to-oxidized glutathione ratio (GSH/GSSG). In addition, p47^phox and gp91^phox (NOX2 subunits) mRNA levels were also high (~3-fold in HFD mice compared to controls), while protein levels were 6.8- and 1.6-fold higher, respectively. Using apocynin (NOX2 inhibitor) during the HFD feeding period, the oxidative intracellular environment was diminished and skeletal muscle insulin-dependent glucose uptake restored. Our results indicate that insulin-resistant mice have increased H₂O₂ release upon insulin stimulation when compared with control animals, which appears to be mediated by an increase in NOX2 expression.     

Ion-exchange resins modified with metal-porphyrin as a catalysis for oxidation of epinephrine (adrenaline)

To develop a solid catalyst which can be a model of catechol oxidase and/or catecholamine monoamine oxidase, the ion-exchange resins modified with metal-tetrakis(4-sulfophenyl)porphine (M-TSPP wherein M is Mn³⁺, Co³⁺, Fe³⁺ or Cu²⁺) were examined for a catalytic activity in the oxidative reaction of epinephrine (adrenaline, Ad). Among M-TSPP-modified resins (M-TSPP_rs), Mn-TSPP_r exhibited the strongest catalytic activity in the oxidation of Ad with O₂ in the air to adrenochrome and adrenolutin. Mn-TSPP had little catalytic activity in an aqueous solution of Ad. The optimum conditions for the oxidation reaction catalyzed by Mn-TSPP_r were determined. Oxidation of catecholamines and related compounds thereof were conducted under the optimum conditions thus determined, which revealed that Mn-TSPP_r only catalyzes oxidation of catecholamines.     

Electrochemical oxidation of sulfide ion at a Ti/IrO<Subscript>2</Subscript>–Ta<Subscript>2</Subscript>O<Subscript>5</Subscript> anode in the presence and absence of naphthenic acids

Electrochemical oxidation of sulfide ion at a Ti/IrO₂–Ta₂O₅ anode followed partial order kinetics (between current and mass transport control) in the absence and presence of chloride ion and of naphthenic acids, at sulfide concentrations typical of sour brines. The desired outcome was to promote the 2-electron oxidation of sulfide to elemental sulfide rather than the 8-electron oxidation to sulfate. Although elemental sulfur accumulated to some extent at low conversion of sulfide, sulfate ion became the principal product as the reaction progressed. At high conversion, the overall current efficiencies were typically higher than 50%, with material balance about 90%. However, this anode material was gradually poisoned by sulfide in long term use.     

Sustainable Process for Production of Azelaic Acid Through Oxidative Cleavage of Oleic Acid

This work describes two sustainable methods for production and purification of azelaic acid (AA) to replace the current process of ozonolysis of oleic acid (OA). The first proceeds in two steps, coupling smooth oxidation of OA to 9,10‐dihydroxystearic acid (DSA) with subsequent oxidative cleavage by sodium hypochlorite. An alternative methodology is also proposed, using a chemocatalytic system consisting of H₂O₂/H₂WO₄ for direct oxidative cleavage of the double bond of OA at 373 K. A convenient technique for separation and purification of azelaic acid is also proposed.     

Phase cooperation of V<Subscript>2</Subscript>O<Subscript>5</Subscript> and Bi<Subscript>2</Subscript>O<Subscript>3</Subscript> in the selective oxidation of H<Subscript>2</Subscript>S containing ammonia and water

The selective oxidation of hydrogen sulfide containing excess water and ammonia was studied over vanadium oxide-based catalysts. The investigation was focused on the role of V₂O₅, and phase cooperation between V₂O₅ and Bi₂O₃ in this reaction. The conversion of H₂S continued to decrease since V₂O₅ was gradually reduced by treatment with H₂S. The activity of V₂O₅ was recovered by contact with oxygen. A strong synergistic phenomenon in catalytic activity was observed for the mechanically mixed catalysts of V₂O₅ and Bi₂O₃. Temperature-programmed reduction (TPR) and oxidation (TPO) and two bed reaction tests were performed to explain this synergistic effect by the reoxidation ability of Bi₂O₃. This paper is dedicated to Professor Wha Young Lee on the occasion of his retirement from Seoul National University.     

Impact of dissolved wastewater constituents on peroxidase‐catalyzed treatment of phenol

The impact of dissolved wastewater constituents on the treatment of synthetic phenol solutions using horseradish peroxidase (HRP) and hydrogen peroxide was investigated under a variety of reaction conditions. The constituents studied included various inorganic salts, organic compounds and heavy metals. Higher H₂O₂ doses were required to treat phenol in the presence of sodium sulfite, thiosulfate and sulfide; however, enhanced levels of phenol conversion were achieved once sufficient H₂O₂ was supplied. Sulfide and cyanide inhibited phenol transformation. The inhibition of sulfide was overcome by supplying sufficient H₂O₂ to oxidize the sulfide to sulfur. However, increasing the H₂O₂ dose was ineffective in attempting to overcome the strong inhibiting effect of cyanide. Among the heavy metal ions tested, only Mn(II) substantially inhibited phenol removal when it was present at a concentration of 1 mmol dm^?3. The presence of inorganic salts including NaCl, CaCl₂, MgCl₂, NH₄Cl and (NH₄)₂SO₄ reduced phenol conversion as compared with the treatment in distilled‐deionized water. This can be attributed to the increased ionic strength of the solution. © 2002 Society of Chemical Industry     

Reduction of Oxidative Stress Attenuates Lipoapoptosis Exacerbated by Hypoxia in Human Hepatocytes

Chronic intermittent hypoxia, a characteristic of obstructive sleep apnea (OSA), is associated with the progression of simple hepatic steatosis to necroinflammatory hepatitis. We determined whether inhibition of a hypoxia-induced signaling pathway could attenuate hypoxia-exacerbated lipoapoptosis in human hepatocytes. The human hepatocellular carcinoma cell line (HepG2) was used in this study. Palmitic acid (PA)-treated groups were used for two environmental conditions: Hypoxia (1% O₂) and normoxia (20% O₂). Following the treatment, the cell viability was determined by the 3,4-(5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay, and the mechanism of lipoapoptosis was evaluated by Western blotting. Hypoxia exacerbated the suppression of hepatocyte growth induced by palmitic acid via activation of mitochondrial apoptotic pathways as a result of endoplasmic reticulum (ER) and oxidative stresses. Ammonium pyrrolidine dithiocarbamate, a scavenger of reactive oxygen species, attenuated the hypoxia-exacerbated lipoapoptosis in hepatocytes, whereas glycerol, which reduces ER stress, did not. This may have been because inhibition of oxidative stress decreases the expression of pro-apoptotic proteins, such as caspase 9 and cytochrome c. These results suggested that modulation of apoptotic signaling pathways activated by oxidative stress can aid in identifying novel therapeutic strategies for the treatment of nonalcoholic steatohepatitis (NASH) with OSA. Further in vivo studies are necessary to understand the pathophysiologic mechanism of NASH with OSA and to prove the therapeutic effect of the modulation of the signaling pathways.     

MiR-25 Protects Cardiomyocytes against Oxidative Damage by Targeting the Mitochondrial Calcium Uniporter

MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H₂O₂, and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3'' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H₂O₂-induced elevation of mitochondrial Ca²⁺ concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes.     

Infrared study of acetone and nitrogen oxides on Cu-ZSM-5

The oxidation of bulky thioethers has been carried out on Ti-Beta and Ti-MCM-41 catalysts, using H₂O₂ andt-butyl hydroperoxide (TBHP) as oxidants. The intrinsic activity of Ti-Beta was higher than that of Ti-MCM-41 for the oxidation of methyl phenyl sulfide which can penetrate in the pores of Beta, while in the case of the larger isopentyl phenyl sulfide, which diffuses more slowly in Ti-Beta zeolite, Ti-MCM-41 gives a larger activity. Ti-Beta is able to perform better for the more demanding oxidation of sulfoxides to sulfones giving, therefore, higher selectivities to sulfones than Ti-MCM-41. Similar results were obtained when using either H₂O₂ or TBHP as oxidants. However, the sterical effects were enhanced when TBHP was used as oxidant.     

Effects of Liposome and Cardiolipin on Folding and Function of Mitochondrial Erv1

Erv1 (EC number 1.8.3.2) is an essential mitochondrial enzyme catalyzing protein import and oxidative folding in the mitochondrial intermembrane space. Erv1 has both oxidase and cytochrome c reductase activities. While both Erv1 and cytochrome c were reported to be membrane associated in mitochondria, it is unknown how the mitochondrial membrane environment may affect the function of Erv1. Here, in this study, we used liposomes to mimic the mitochondrial membrane and investigated the effect of liposomes and cardiolipin on the folding and function of yeast Erv1. Enzyme kinetics of both the oxidase and cytochrome c reductase activity of Erv1 were studied using oxygen consumption analysis and spectroscopic methods. Our results showed that the presence of liposomes has mild impacts on Erv1 oxidase activity, but significantly inhibited the catalytic efficiency of Erv1 cytochrome c reductase activity in a cardiolipin-dependent manner. Taken together, the results of this study provide important insights into the function of Erv1 in the mitochondria, suggesting that molecular oxygen is a better substrate than cytochrome c for Erv1 in the yeast mitochondria.     

DHA Protects Hepatocytes from Oxidative Injury through GPR120/ERK-Mediated Mitophagy

Oxidative stress occurs in a variety of clinical liver diseases and causes cellular damage and mitochondrial dysfunction. The clearance of damaged mitochondria by mitophagy may facilitate mitochondrial biogenesis and enhance cell survival. Although the supplementation of docosahexaenoic acid (DHA) has been recognized to relieve the symptoms of various liver diseases, the antioxidant effect of DHA in liver disease is still unclear. The purpose of our research was to investigate the antioxidant effect of DHA in the liver and the possible role of mitophagy in this. In vitro, H₂O₂-induced injury was caused in AML12 cells. The results showed that DHA repressed the level of reactive oxygen species (ROS) induced by H₂O₂ and stimulated the cellular antioxidation response. Most notably, DHA restored oxidative stress-impaired autophagic flux and promoted protective autophagy. In addition, PINK/Parkin-mediated mitophagy was activated by DHA in AML12 cells and alleviated mitochondrial dysfunction. The ERK1/2 signaling pathway was inhibited during oxidative stress but reactivated by DHA treatment. It was proven that the expression of ERK1/2 was involved in the regulation of mitophagy by the ERK1/2 inhibitor. We further proved these results in vivo. DHA effectively alleviated the liver oxidative damage caused by CCl₄ and enhanced antioxidation capacity; intriguingly, autophagy was also activated. In summary, our data demonstrated that DHA protected hepatocytes from oxidative damage through GPR120/ERK-mediated mitophagy.     

Highly Efficient Route to Diselenides from the Reactions of Imines and Selenium in the Presence of Carbon Monoxide and Water

Reactions of selenium with imines (RR¹CNR²) of aldehydes and ketones in the presence of carbon monoxide, water and triethylamine lead to reductive selenation, on aerobic work‐up, to afford symmetrical diselenides (RR¹CHSe)₂ in good to excellent yields. The proposed mechanism suggests that both in situ generated carbonyl selenide (SeCO) and hydrogen selenide (H₂Se) are involved in the reaction.