Benzeneseleninic Acid Research Articles

Synthesis of Selenium-Decorated N-Oxide Isoquinolines: Arylseleninic Acids in Selenocyclization Reactions.

Herein, we describe the use of benzeneseleninic acid derivatives (BSA) as a bench-stable and easy to handle selenium reagent to access 4-(selanyl)isoquinoline-N-oxides through the selenocyclization of o-alkynyl benzaldehyde oximes. The reaction is conducted in refluxing methanol, allowing the thermal generation of electrophilic selenium species in situ. By this new protocol, a library of 19 selenium-decorated N-oxide isoquinolines was accessed in up to 96% yield with an outstanding substrate tolerance and the feasibility to scale it up 10 times (from 0.25 to 2.5 mmol).

Benzeneseleninic acid used as an oxidizing and deprotecting reagent for the synthesis of multi-cyclic peptides constrained by multiple disulfide bonds and thioether bridges

New methodologies based on benzeneseleninic acid (BSA) were designed to efficiently synthesize multiple disulfide bonds or thioether bridges in peptides in a one-pot manner in which BSA dually functioned as an oxidant and a deprotecting reagent.

Chemistry Related to the Catalytic Cycle of the Antioxidant Ebselen.

The antioxidant drug ebselen has been widely studied in both laboratories and in clinical trials. The catalytic mechanism by which it destroys hydrogen peroxide via reduction with glutathione or other thiols is complex and has been the subject of considerable debate. During reinvestigations of several key steps, we found that the seleninamide that comprises the first oxidation product of ebselen underwent facile reversible methanolysis to an unstable seleninate ester and two dimeric products. In its reaction with benzyl alcohol, the seleninamide produced a benzyl ester that reacted readily by selenoxide elimination, with formation of benzaldehyde. Oxidation of ebselen seleninic acid did not afford a selenonium seleninate salt as previously observed with benzene seleninic acid, but instead generated a mixture of the seleninic and selenonic acids. Thiolysis of ebselen with benzyl thiol was faster than oxidation by ca. an order of magnitude and produced a stable selenenyl sulfide. When glutathione was employed, the product rapidly disproportionated to glutathione disulfide and ebselen diselenide. Oxidation of the S-benzyl selenenyl sulfide, or thiolysis of the seleninamide with benzyl thiol, afforded a transient thiolseleninate that also readily underwent selenoxide elimination. The S-benzyl derivative disproportionated readily when catalyzed by the simultaneous presence of both the thiol and triethylamine. The phenylthio analogue disproportionated when exposed to ambient or UV (360 nm) light by a proposed radical mechanism. These observations provide additional insight into several reactions and intermediates related to ebselen.

Benzeneseleninic Acid Promoting the Selenofunctionalization of 2- Naphthol Derivatives: Synthesis and Antioxidant Activity of 1- Organoselanyl-naphthalen-2-ols

Background: We report the synthesis and antioxidant evaluation of 1-organoselanyl-naphthalen-2-ols. The title compounds were selectively prepared through the selenofunctionalization of 2-naphthol derivatives using benzeneseleninic acids as a selenium source. Objective: We aimed at synthesizing 1-organoselanyl-naphthalen-2-ol by functionalizing 2-naphthol with arylseleninic acids using glycerol as the solvent and further evaluating the pharmacological activity. Methods: The products were synthesized at 70 °C using glycerol as a solvent in an oil bath. Reactive species (RS) tests, DPPH radical scavenging activity assay, and ABTS+ radical scavenging activity assay were performed. A statistical analysis of the data was performed. Results and Discussion: A total of fifteen 1-organoselanyl-naphthalen-2-ols were selectively obtained in yields of 58-95% in 0.25-48 h of reaction. Additionally, all the synthesized seleno-derivatives exhibited antioxidant activity, as revealed by their ability to scavenge DPPH and ABTS+ radicals and reduce the reactive species (RS) levels. Conclusion: The synthesis of 1-arylselanyl-naphthalen-2-ols was developed under mild reaction conditions using benzeneseleninic acid derivatives in reactions with 2-naphthol. All synthesized 2-naphthol derivatives exhibited antioxidant activity, as revealed by their DPPH and ABTS+ radical scavenging activity and reduced RS levels.

Visible‐Light‐Mediated Photocatalytic Synthesis of 2‐Substituted Oxazole‐5‐carbaldehydes Promoted by Benzeneseleninic Acid

AbstractBenzeneseleninic acid was used under visible light irradiation (white LEDs) to promote the oxidative cyclization of N‐propargyl amides to the respective 2‐substituted oxazole‐5‐carbaldehydes. A total of twelve 2‐aryl oxazole‐5‐carbaldehydes, six of them so far unprecedented, were prepared in 30–90 % yield in just 1 hour of reaction at room temperature. No metal catalysts, nor strong oxidants or heating were necessary, making this a mild method to access a valuable class of compounds. The only co‐products are water and diphenyl diselenide, that can be recovered and converted to new benzeneseleninic acid for a new reaction.

Seleninic Acid Potassium Salts as Water-Soluble Biocatalysts with Enhanced Bioavailability.

Organoselenium compounds are well-known glutathione peroxidase (GPx) mimetics that possess antioxidants/prooxidant properties and are able to modulate the concentration of reactive oxygen species (ROS), preventing oxidative stress in normal cells or inducing ROS formation in cancer cells leading to apoptosis. The purpose of this study was the synthesis of potent GPx mimics with antioxidant and anticancer activity along with improved bioavailability, as a result of good solubility in protic solvents. As a result of our research, glutathione peroxidase (GPx) mimetics in the form of water-soluble benzeneseleninic acid salts were obtained. The procedure was based on the synthesis of 2-(N-alkylcarboxyamido)benzeneselenenic acids, through the oxidation of benzisoselenazol-3(2H)-ones or analogous arenediselenides with an amido group, which were further converted to corresponding potassium salts by the treatment with potassium tert-butanolate. All derivatives were tested as potential antioxidants and anticancer agents. The areneseleninic acid salts were significantly better peroxide scavengers than analogous acids and the well-known organoselenium antioxidant ebselen. The highest activity was observed for the 2-(N-ethylcarboxyamido)benzeneselenenic acid potassium salt. The strongest cytotoxic effect against breast cancer (MCF-7) and human promyelocytic leukemia (HL-60) cell lines was found for 2-(N-cyclohexylcarboxyamido)benzeneselenenic acid potassium salt and the 2-(N-ethylcarboxyamido)benzeneselenenic acid, respectively. The structure–activity correlations, including the differences in reactivity of benzeneseleninic acids and corresponding salts were evaluated.

The Unexpected Role of SeVISpecies in Epoxidations with Benzeneseleninic Acid and Hydrogen Peroxide

AbstractBenzeneperoxyseleninic acid has been proposed as the key intermediate in the widely used epoxidation of alkenes with benzeneseleninic acid and hydrogen peroxide. However, it reacts sluggishly with cyclooctene and instead rapidly decomposes in solution to a mixed selenonium–selenonate salt that was identified by X‐ray absorption and77Se NMR spectroscopy, as well as by single crystal X‐ray diffraction. This process includes a selenoxide elimination of the peroxyseleninic acid with liberation of oxygen and additional redox steps. The salt is relatively stable in the solid state, but generates the corresponding selenonic acid in the presence of hydrogen peroxide. The selenonic acid is inert towards cyclooctene on its own; however, rapid epoxidation occurs when hydrogen peroxide is added. This shows that the selenonic acid must first be activated through further oxidation, presumably to the heretofore unknown benzeneperoxyselenonic acid. The latter is the principal oxidant in this epoxidation.

The Unexpected Role of SeVI Species in Epoxidations with Benzeneseleninic Acid and Hydrogen Peroxide.

Benzeneperoxyseleninic acid has been proposed as the key intermediate in the widely used epoxidation of alkenes with benzeneseleninic acid and hydrogen peroxide. However, it reacts sluggishly with cyclooctene and instead rapidly decomposes in solution to a mixed selenonium-selenonate salt that was identified by X-ray absorption and 77 Se NMR spectroscopy, as well as by single crystal X-ray diffraction. This process includes a selenoxide elimination of the peroxyseleninic acid with liberation of oxygen and additional redox steps. The salt is relatively stable in the solid state, but generates the corresponding selenonic acid in the presence of hydrogen peroxide. The selenonic acid is inert towards cyclooctene on its own; however, rapid epoxidation occurs when hydrogen peroxide is added. This shows that the selenonic acid must first be activated through further oxidation, presumably to the heretofore unknown benzeneperoxyselenonic acid. The latter is the principal oxidant in this epoxidation.

Photocatalytic treatment of mixed selenocyanate and phenol streams: Process modeling, optimization, and kinetics

AbstractElevated selenium presence in the aquatic bodies because of increased industrial practices and the resulting toxicity concerns have prompted selenium treatment. Although most studies have focused on selenite (SeO32−) and selenate (SeO42−) removal, however selenocyanate (SeCN−) is another Se‐species whose treatment is challenging often because of a complex wastewater matrix and presence of co‐pollutants such as phenol. The present study therefore investigated the efficiency of TiO2 photocatalysis (with EDTA as a hole/h+ scavenger) for the treatment of mixed selenocyanate/phenol wastewater along with response surface methodology (RSM) based process optimization, determination of reaction intermediates, and kinetic modeling. The application of face‐centered central composite design (CCD) RSM modeling yielded Natural Log Transformed Linear model for selenium removal, and non‐transformed two‐factor interaction model for phenol removal. These models were duly validated using statistical tools, and then tested employing additional experiments. The optimal process conditions for maximum selenium and phenol removal were found to be pH 4, 10 ppm selenocyanate, 5 ppm phenol, and 450 ppm EDTA. Findings from the reaction byproducts analysis indicated selenite, selenate, benzenediols, and benzeneseleninic acid as most noted intermediates. A kinetic model that predicts the changes in parent compounds selenocyanate/phenol and dominant reaction intermediates during photocatalysis is also presented.

Can dimedone be used to study selenoproteins? An investigation into the reactivity of dimedone toward oxidized forms of selenocysteine.

Dimedone is a widely used reagent to assess the redox state of cysteine-containing proteins as it will alkylate sulfenic acid residues, but not sulfinic acid residues. While it has been reported that dimedone can label selenenic acid residues in selenoproteins, we investigated the stability, and reversibility of this label in a model peptide system. We also wondered whether dimedone could be used to detect seleninic acid residues. We used benzenesulfinic acid, benzeneseleninic acid, and model selenocysteine-containing peptides to investigate possible reactions with dimedone. These peptides were incubated with H2 O2 in the presence of dimedone and then the reactions were followed by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS). The native peptide, H-PTVTGCUG-OH (corresponding to the native amino acid sequence of the C-terminus of mammalian thioredoxin reductase), could not be alkylated by dimedone, but could be carboxymethylated with iodoacetic acid. However the "mutant peptide," H-PTVTGAUG-OH, could be labeled with dimedone at low concentrations of H2 O2 , but the reaction was reversible by addition of thiol. Due to the reversible nature of this alkylation, we conclude that dimedone is not a good reagent for detecting selenenic acids in selenoproteins. At high concentrations of H2 O2 , selenium was eliminated from the peptide and a dimeric form of dimedone could be detected using LCMS and 1 H NMR. The dimeric dimedone product forms as a result of a seleno-Pummerer reaction with Sec-seleninic acid. Overall our results show that the reaction of dimedone with oxidized cysteine residues is quite different from the same reaction with oxidized selenocysteine residues.

Syntheses and structural characterization of organotin complexes derived from 2-(trifluoromethyl)benzeneseleninic acid: tetranuclear macrocycle, 1-D polymeric chain, helical double-chain

Four organotin(IV) complexes based on 2-(trifluoromethyl)benzeneseleninic acid, [Me3Sn(O2SeC6H4-2-CF3)]4 (1), [Ph3Sn(O2SeC6H4-2-CF3)]n (2), [R2Sn(O2SeC6H4-2-CF3)2]n (R = Me 3; n-Bu 4), have been synthesized and characterized by X-ray diffraction, elemental analysis, infrared spectroscopy, and NMR (1H, 13C and 119Sn) spectroscopy. Single-crystal X-ray analyses show that 1 has a centrosymmetric tetranuclear triorganotin selenite with a tetranuclear 16-membered macrocycle formed by trimethyltin and ligand alternately linking; 2 exhibits a 1-D neutral infinite chain structure in which the [O2SeC6H4-2-CF3]− is a μ2-bridging ligand; 3 and 4 are polymeric chain structures containing Sn2O4Se2 eight-membered rings where the areneseleninate groups are double bridges between the tin ions. Examination of the intermolecular contacts of 1 reveals the existence of the C–H⋯O hydrogen bonding interactions and C–H⋯π interactions. Weak C–H⋯O interactions were also found to be important for the formation of the 3-D structure for 3.

A Photo‐responsive Catalytic Vesicle with GPx Activity

AbstractGlutathione peroxidase (GPx) is a vital antioxidant enzyme involved in the reduction of reactive oxygen species and protects cells from oxidative damage. Consequently enormous efforts have been devoted to developing artificial catalysts with GPx function. Besides the research on enhancing the catalytic activity of GPx mimics, the design and construction of smart GPx models has also inspired great interest. Herein, a novel photo‐responsive selenium‐containing vesicular GPx model was successfully constructed by supramolecular self‐assembly of the cationic surfactant PyC10AzoC10Py with benzeneseleninic acid (PhSeO2H) through hydrophobic and electrostatic interactions in aqueous media. This selenium‐containing vesicular catalyst showed remarkable GPx‐like activity, which is 692 times more effective than PhSeO2H for the reduction of cumene hydroperoxide (CUOOH) by 4‐nitrobenzenethiol (NBT). Interestingly, when an equimolar amount of α‐CD was added, the GPx‐like activity of the catalytic vesicle declines remarkably due to the vesicle disaggregation in the presence of α‐CD. Whereas the biomimetic system was irradiated by UV light at 365 nm, the catalytic vesicle was formed again and the GPx‐like activity recovered.

12‐Membered Macrocycles Containing Ditelluroxane and Selenotelluroxane Units

AbstractThe reaction of benzeneseleninic acid with bis(p‐methoxyphenyl)tellurium dihalide [halide = Cl (1), Br (2)] afforded colorless crystals in moderate yield. Single‐crystal X‐ray diffraction revealed the formation of 12‐membered macrocycles [(p‐MeO‐C6H4)2Te(μ‐O)(μ‐PhSeO2)(μ4‐X)]2 [X = Cl (1), Br (2)] where the halogen atoms, which are stabilized by Te–X interactions, cap the macrocycle on both sides. The reaction of NaI with 1 afforded the iodo‐capped macrocycle [(p‐MeO‐C6H4)2Te(μ‐O)(μ‐PhSeO2)(μ4‐I)]2 (3) in good yield. In the solid‐state structures of 1–3, the alignment of the phenyl group on Se changes with respect to the macrocycle. Macrocycle 3 shows rare Se–π interactions, which lead to the formation of a supramolecular polymeric network. Further reaction of methaneseleninic acid with bis(p‐methoxyphenyl)tellurium dichloride in methanol in the presence of triethylamine afforded a 12‐membered macrocycle [(p‐MeO‐C6H4)2Te(μ‐O)(μ‐MeSeO2)(μ4‐Cl)]2 (4), which is structurally similar to 1–3.

Syntheses and characterization of diorganotin(IV) derivatives with areneseleninic acid: X-ray crystal structures of 1D infinite chains containing eight-membered ring

Three new diorganotin(IV) derivatives with areneseleninic acids, [Bu 2 Sn(O 2 SeC 6 H 5 ) 2 ] n ( 1 ), [Bu 2 Sn(O 2 SeC 6 H 4 Me) 2 ] n ( 2 ) and [Me 2 Sn(O 2 SeC 6 H 4 Bu) 2 ] n ( 3 ) have been synthesized and characterized. X-ray diffraction studies of 1 , 2 , 3 show that the areneseleninate groups behave as double bridges between the tin atoms leading to polymeric ringchain structure with Sn 2 O 4 Se 2 eight-membered rings. ► Three new diorganotin(IV) derivatives with areneseleninic acids were synthesized. ► Crystal structures show that all the complexes exhibit 1D chain structures. ► The areneseleninate groups behave as double bridges. Three new diorganotin(IV) complexes, [Bu 2 Sn(O 2 SeC 6 H 5 ) 2 ] n ( 1 ), [Bu 2 Sn(O 2 SeC 6 H 4 Me) 2 ] n ( 2 ), [Me 2 Sn(O 2 SeC 6 H 4 Bu) 2 ] n ( 3 ) have been synthesized by the reaction of benzeneseleninic acid, p -tolueneseleninic acid, and 4- tert -butylbenzeneseleninic acid with Me 2 SnCl 2 or Bu 2 SnCl 2 in the presence of sodium ethoxide in methanol at 50 °C. All of the complexes were characterized by elemental analysis, FT-IR, NMR ( 1 H, 13 C and 119 Sn) spectroscopy and X-ray crystallography. X-ray diffraction studies of 1 , 2 , 3 show that the areneseleninate groups behave as double bridges between the tin atoms leading to polymeric chain structure with Sn 2 O 4 Se 2 eight-membered ring. The organic groups bonded to the tin atoms are in trans-position in the resulting octahedral arrangement.

ChemInform Abstract: Facile Oxidation of Sulfides to Sulfoxides Using Iodosobenzene and Benzeneseleninic Acid as a Catalyst.

Abstract Iodosobenzene in the presence of catalytic amount of benzeneseleninic acid oxidized various sulfides to sulfoxides through ligand coupling on the iodine atom in excellent yields in acetonitrile under mild conditions.

Model mechanisms of sulfhydryl oxidation by methyl- and benzeneseleninic acid, inhibitors of zinc-finger transcription factors

The toxicity of selenium is a major barrier to its application to the prevention of cancer, cardiovascular disease, and other chronic ailments. Organic seleninic acids, as well as other reducible selenium compounds, have been shown to react with biological sulfhydryls to disrupt a variety of biochemical signaling pathways, including transcription and recognition by zinc-finger proteins. Using density-functional theory (DFT) and solvent-assisted proton exchange, the thiol reduction mechanisms of methyl- and benzeneseleninic acid have been modeled as distinct two-step pathways with intermediates as either a seleninyl sulfide or a hypervalent selenurane. The activation barrier for the first step to the selenurane intermediate is 10-13kcal/mol lower than the seleninyl sulfide. For the second step, reduction of the selenurane is slightly more energetically favorable than for the seleninyl sulfide, primarily due to the implicit solvation correction. The barrier for step two using either intermediate is greater than that of the first step which is consistent with experimental studies that assign the reduction of the intermediate as the rate-determining step. The summary of the DFT results suggest that the reaction pathway is (1) addition of thiol to the seleninic acid to form a short-lived selenurane; (2) rearrangement of the selenurane to the seleninyl sulfide; and (3) reduction of the seleninyl sulfide by the second equivalent of thiol.

Reaction of Finasteride Intermediate with Benzeneseleninic Anhydride: An In-Depth Study

One of the intermediates of finasteride was oxidized by the reaction of benzeneseleninic (BS) anhydride in refluxing toluene for 16 h. Sometimes, the desired product was obtained, and sometimes, there was no yield or very low yield at the end of the reaction time. To obtain a better understanding of such variations, laboratory syntheses were conducted with commercial BS anhydride, pure BS anhydride, pure BS acid, and mixtures of anhydride and acid samples. During the reaction, the intermediate reaction masses were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) at predetermined times and correlated with differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) samples. The DSC and XRPD data indicated that commercial BS anhydride samples did not always consist of the pure anhydride form. When the BS acid was present in the anhydride sample, the reaction rate was lower than that of the pure BS anhydride sample.

Biotransformation of β-hydroxyphenyl selenides, diphenyldiselenide and benzeneseleninic acid by whole cells of Aspergillus terreus

Aspergillus terreus CCT 3320 and A. terreus URM 3571 catalysed the biotransformations of organic β-hydroxyphenyl selenides through oxidation and methylation reactions. The kinetic resolution of ( RS )-1-(phenylseleno)-2-propanol ( 1 ) via enantioselective oxidation produced (+)-( S )- 1 in high enantiomeric excess (>99%) and in a yield of 50% as determined by product isolation. Oxidation of the R -enantiomer of 1 , followed by elimination of the propyl moiety and subsequent methylation of the presumed intermediate, led to the formation of methylphenyl-selenide, which was isolated in a yield of 40%. Whole cells of A. terreus also biocatalysed transformations of diphenyldiselenide, benzeneseleninic acid, ( RS )-1-(phenylseleno)-2-pentanol and ( RS )-1-(phenylseleno)-3-methyl-2-butanol, but not of ( RS )-1-(phenylseleno)-2-phenyl-methanol. This is the first report of the biomethylation of organoselenium compounds by whole cells of A. terreus .

Selenium-Mediated Micellar Catalyst: An Efficient Enzyme Model for Glutathione Peroxidase-like Catalysis

Mimicking the properties of the selenoenzyme glutathione peroxidase (GPx) has inspired great interest. In this report, a selenium-containing micellar catalyst was successfully constructed by the self-assembly of the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) with benzeneseleninic acid (PhSeO2H) through hydrophobic and electrostatic interaction in water. The selenium-containing micellar catalyst demonstrated substrate specificity for both 3-carboxy-4-nitrobenzenethiol (ArSH, 2) and cumene hydroperoxide (CUOOH), and their complexation was confirmed by UV and fluorescence spectra. More importantly, it demonstrated high GPx activity in two assay systems. It is about 126 times more effective than the well-known GPx mimic ebselen in the classical coupled reductase assay system; however, by using hydrophobic substrate ArSH (2) as an alternative of glutathione (GSH, 1), the micellar catalyst exhibited remarkable 500-fold and 94 500-fold rate enhancements compared with that of PhSeO2H and PhSeSePh.

Induction of Phase II Enzyme Activity by Various Selenium Compounds

: Twenty-seven selenium compounds and sixteen structurally related organosulfur compounds were tested for quinone reductase (QR) and glutathione-S-transferase (GST) inducing activity in murine hepatoma (Hepa 1c1c7) cells. Sixteen selenium compounds were able to double QR activity, and seven of them also doubled GST activity. The nine most potent compounds, dimethyl diselenide, 2,5-diphenyl- selenophene, dibenzyl diselenide, methylseleninic acid, diphenyl diselenide, benzeneseleninic acid, benzene selenol, triphenylselenonium chloride, and ebselen (2-phenyl- 1,2-benzisoselenazol-3(2H)-one), doubled QR-specific activity at levels lower than 7 μM. The concentration-dependence of QR induction and cell growth inhibition were linearly correlated (P < 0.001, r2 = 0.96) among the group of organoselenium compounds with putative selenol-generating potential, implying that both responses of Hepa 1c1c7 cells were based on these selenol metabolites.