Remarkable activity of a novel cyclic seleninate ester as a glutathione peroxidase mimetic and its facile in situ generation from allyl 3-hydroxypropyl selenide

1,2-Oxaselenolane Se-oxide is a novel cyclic seleninate ester that functions as a remarkably efficient glutathione peroxidase mimetic by catalyzing the reduction of tert-butyl hydroperoxide to tert-butyl alcohol in the presence of benzyl thiol. The seleninate ester can be conveniently generated in situ by oxidation of allyl 3-hydroxypropyl selenide with tert-butyl hydroperoxide. Its catalytic activity surpasses that of several other known GPx mimetics containing cyclic selenenamide structures, which were also tested for comparison.     

Diselenides and allyl selenides as glutathione peroxidase mimetics. Remarkable activity of cyclic seleninates produced in situ by the oxidation of allyl omega-hydroxyalkyl selenides

A series of aliphatic diselenides and selenides containing coordinating substituents was tested for glutathione peroxidase (GPx)-like catalytic activity in a model system in which the reduction of tert-butyl hydroperoxide with benzyl thiol to afford dibenzyl disulfide and tert-butyl alcohol was performed under standard conditions and monitored by HPLC. Although the diselenides showed generally poor catalytic activity, allyl selenides proved more effective. In particular, allyl 3-hydroxypropyl selenide (25) rapidly generated 1,2-oxaselenolane Se-oxide (31) in situ by a series of oxidation and [2,3]sigmatropic rearrangement steps. The remarkably active cyclic seleninate 31 proved to be the true catalyst, reacting with the thiol via a postulated mechanism in which the thioseleninate 32 is first produced, followed by further thiolysis to selenenic acid 33 and oxidation-dehydration to regenerate 31. In contrast to catalysis with GPx, formation of the corresponding selenenyl sulfide 34 comprises a competing deactivation pathway in the catalytic cycle of 31, as a separate experiment revealed that authentic 34 was a much less effective catalyst than 31. 1,2-Oxaselenane Se-oxide (37), the six-membered homologue of 31, was formed similarly from allyl 4-hydroxybutyl selenide (26), but proved a less effective catalyst than 31. Compounds 31 and 37 are the first examples of unsubstituted monocyclic seleninate esters.     

Cyclic and stripping voltammetry of Se(+4) and Se(−2) at the HMDE in acidic media

Electroreduction of Se(+4) and electrooxidation of Se(?2) were studied at mercury electrodes in acidic media and an improved mechanism of the reduction process was proposed. This mechanism takes into account the fact that the reduction path is concentration-dependent. At lower concentrations of Se(+4), mercury selenide and hydrogen selenide are formed at various potentials. At higher Se(+4) concentrations the electrode quickly becomes covered by a rigid deposit of mercury selenide and then the reduction starts to proceed to elemental selenium. Another form of selenium was formed in the vicinity of the mercury surface due to a chemical reaction between H₂SeO₃ and H₂Se. Oxidation of hydrogen selenide proceeds similarly, in the sense that after coverage of the electrode surface by a deposit of mercury selenide the oxidation starts to proceed to elemental selenium. The cathodic stripping peak of mercury selenide can be obtained down to 2 × 10^?8M of Se(+4), but this peak is often split and therefore the determination of traces of Se(+4) by the cathodic stripping technique is cumbersome.     

Enhancement of Sensitivity for Selenium Determination in Atomic Absorption Spectrophotometry by Introducting Hydrogen Selenide into an Argon-Hydrogen Flame

Abstract

The sensitivity for selenium determination with atomic absorption spectrophotometry is enhanced to a large extent by introducing hydrogen selenide gas into an argon-hydrogen flame. As a reducing agent, zinc granular and stannous chloride is successfully used for quantitative and rapid productions of hydrogen selenide from selenium(IV) solution. The sensitivity for 1 % absorption of the signal is estimated to be about 0.02 ppm of selenium.     

Electrodeposition of Copper Selenide onto Mo Electrode in Tartaric Acid Solution

Results are presented of a study of the electrochemical behavior of copper(II) and selenium(IV) ions and their joint reduction on a molybdenum electrode by cyclic voltammetry in a tartaric acid electrolyte. The potentiostatic deposition was used to obtain copper selenide deposits on Mo plates. The diffraction and energydispersive analyses demonstrated that a Cu_2?xSe compound is formed with an admixture of the CuSe phase. A suggestion is made that the process of underpotential reduction affects the formation of copper selenide. Copper selenide films were deposited at a potential of ?0.6 V in the course of 30 min with a thickness of 0.43 μm and high adhesion to the substrate. At potentials in this range, an additional amount of the deposit may be formed due to the chemical reaction between Cu⁺ and Se^2? ions. The p-type conduction was determined for films electrodeposited at various potentials.     

Aromatic derivatives and tellurium analogues of cyclic seleninate esters and spirodioxyselenuranes that act as glutathione peroxidase mimetics

[Reaction: see text]. Several novel organoselenium and tellurium compounds were prepared and evaluated as mimetics of the selenoenzyme glutathione peroxidase, which protects cells from oxidative stress by reducing harmful peroxides with the thiol glutathione. The compounds were tested for catalytic activity in a model system wherein tert-butyl hydroperoxide or hydrogen peroxide were reduced with benzyl thiol and the rate of the reaction was measured by monitoring the formation of dibenzyl disulfide. Thus, aromatic derivatives 19, 22, 24, and 25 proved to be inferior catalysts compared to the parent cyclic seleninate ester 14 and spirodioxyselenurane 16. In the case of 19 and 22, this was the result of their rapid conversion to the relatively inert selenenyl sulfides 31 and 32, respectively. In general, hydrogen peroxide was reduced faster than tert-butyl hydroperoxide in the presence of the selenium-based catalysts. The cyclic tellurinate ester 27 and spirodioxytellurane 29 proved to be superior catalysts to their selenium analogues 14 and 16, respectively, resulting in the fastest reaction rates by far of all of the compounds we have investigated to date. Oxidation of 29 with hydrogen peroxide produced the unusual and unexpected peroxide 33, in which two hypervalent octahedral tellurium moieties are joined by ether and peroxide bridges. The structure of 33 was confirmed by X-ray crystallography. Although 33 displayed strong catalytic activity when tested independently in the model system, its relatively slow formation from the oxidation of 29 rules out its intermediacy in the catalytic cycle of 29.     

Glutathione peroxidase (GPx)-like antioxidant activity of the organoselenium drug ebselen: unexpected complications with thiol exchange reactions

The factors that are responsible for the relatively low glutathione peroxidase (GPx)-like antioxidant activity of organoselenium compounds such as ebselen (1, 2-phenyl-1,2-benzisoselenazol-3(2H)-one) in the reduction of hydroperoxides with aromatic thiols such as benzenethiol and 4-methylbenzenethiol as cosubstrates are described. Experimental and theoretical investigations reveal that the relatively poor GPx-like catalytic activity of organoselenium compounds is due to the undesired thiol exchange reactions that take place at the selenium center in the selenenyl sulfide intermediate. This study suggests that any substituent that is capable of enhancing the nucleophilic attack of thiol at sulfur in the selenenyl sulfide state would enhance the antioxidant potency of organoselenium compounds such as ebselen. It is proved that the use of thiol having an intramolecularly coordinating group would enhance the biological activity of ebselen and other organoselenium compounds. The presence of strong S...N or S...O interactions in the selenenyl sulfide state can modulate the attack of an incoming nucleophile (thiol) at the sulfur atom of the -Se-S- bridge and enhance the GPx activity by reducing the barrier for the formation of the active species selenol.     

Selenium assisted carbonylation of alkyl aryl ketones with carbon monoxide

Selenium assisted carbonylation of alkyl aryl ketones with carbon monoxide leading to formation of 1,3-dicarbonyl compounds as C-carbonylated products is described. o-Hydroxyacetophenone 7a and its derivatives7b,7c, and 7d have been converted to the corresponding 4-hydroxycoumarins 8a,8b,8c and 8d in moderate to quantitative yields by treatment with an equivalent of selenium and carbon monoxide with concomitant formation of hydrogen selenide 9 (Eq.(8)). It was further revealed that oxidation of in situ formed hydrogen selenide to selenium with an appropriate oxidizing agent such as nitrobenzene permitted catalytic use of selenium for the carbonylation of 7. Possible rationalizations for the formation of 4-hydroxycoumarins are suggested.     

Synthesis,crystal structures and magnetic properties of two iron (II) tris(pyridyl)phosphine selenides complexes

We reported the synthesis of tris(pyridyl)phosphine selenide (TppSe) and tris(4-methylpyridin-2-yl)phosphine selenide (MeTppSe), which were prepared by a simple and straightforward one-pot method with red phosphorus in a KOH/DMSO suspension, and treatment of resulted phosphines with selenium in hot toluene. These compounds were characterized by mass spectroscopy, ¹H, ¹³C and ³¹P NMR spectroscopies and the structure of MeTppSe was characterised by a single-crystal X-ray diffraction. Furthermore, The reactions of selenides with Fe(ClO₄)₂·6H₂O afforded two new iron(II) mononuclear metal complexes [Fe(TppSe)₂][ClO₄]₂·3DMF (1) and [Fe(MeTppSe)₂][ClO₄]₂·2DMF (2). Detailed structural analyses and magnetic susceptibility measurements confirm no spin transition from low-spin to the high-spin state between 2 and 300 K in two iron(II) complexes.     

Pyrolysis of Dibenzyl Selenides to Bibenzyls

The formation of carbon-carbon bond by sulfur extrusion such as pyrolysis of cyclic sulfones is well known as an important synthetic method, especially for the synthesis of cyclophane framework.¹⁾ Little is known about selenium extrusion as the counterpart, though organoseleniums have been properly appreciated as a useful tool for manipulating a functional group.²⁾ Lardon reported that the thermal decomposition of dibenzyl diselenide led to a mixture of dibenzyl selenide and polyselenides.³⁾ In contrast, recent reports showed that at 210°C, heating bis(diphenylmethyl) diselenide resulted in ready selenium extrusion to 1,1,2,2-tetraphenylethane⁴⁾, and dianthrylmethyl mono- and diselenides to 1,2-dianthrylethane.⁵⁾ Therefore,- it is worthwhile to study the thermal behavior of dibenzyl selenide itself.     

Photometric determination of trace selenium in aqueous media

A new procedure is developed for the photometric determination of trace selenium in aqueous solutions. The selection of 2-(p-nitrophenyl)-3,5-diphenyltetrazolium chloride as a reagent for selenium is justified. The proposed sample preparation procedure involves gas extraction of selenium as hydrogen selenide followed by its liquid-adsorption extraction from the gas phase to an aqueous reagent solution with the formation of a water-insoluble formazan. Formazan formed upon the absorption of hydrogen selenide is extracted with isoamyl alcohol. The concentration of selenium is determined from the absorbance of the formazan extract in the isoamyl alcohol. The procedure allows the determination of 10–120 μg/L selenium.     

Synthesis and characterization of novel quinoline selenium compounds: X-ray structure of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline

A series of novel and synthetically important quinoline selenium compounds have been successfully synthesized using an efficient and simple strategy. The method employed leads to the synthesis of both cyclic as well as open chain quinoline selenium compounds. The prepared selenium compounds have been characterized with the help of various spectroscopic techniques viz., NMR (¹H, ¹³C), FT-IR, mass spectrometry. The structure of 6-methoxy-3H-[1,2]diselenolo[3,4-b]quinoline has been determined by X-ray crystallography.     

Studies of the naturally occurring biomethylation of selenium and the determination of the products

A systematic study of the biomethylation of selenium and the determination of the methylated species indicates preliminarily that selenium is susceptible to natural biomethylation under certain environmental conditions. Detectable levels of methylated selenium species, including dimethyl selenide [(CH₃)₂Se], dimethyl diselenide [(CH₃)₂Se₂] and dimethylselenone [(CH₃)₂SeO₂] have been detected by gas chromatography – graphite furnace atomic absorption spectrophotometry (GC – GF AA) from a variety of environmental samples. Findings of naturally methylated selenium species from both soil samples and related air samples suggest that there may exist a localized cycle of selenium between ground soil and the ambient air. Factors that influence the sensitivity and accuracy for the determination of alkyl selenide compounds by GC – GF AA have also been investigated. Flashlike injection mode and addition of about 10% of hydrogen gas to the argon carrier gas provide for highly sensitive detection. Reproducible determination can be obtained with a precision of about 6% and the detection limits are 0.3 ng Se m^?3.     

A simple and efficient strategy to enhance the antioxidant activities of amino-substituted glutathione peroxidase mimics

The glutathione peroxidase (GPx) activities of some diaryl diselenides incorporating tertiary amino groups were studied with H(2)O(2), Cum-OOH, and tBuOOH as substrates and with PhSH as thiol co-substrate. Simple replacement of a hydrogen atom with a methoxy group dramatically enhances the GPx activity. The introduction of methoxy substituents ortho to selenium in N,N-dialkylbenzylamine-based compounds makes the basicity of the amino groups perfect for the catalysis. The presence of 6-OMe groups prevents possible SeN interactions in the selenols, increasing their zwitterionic characters. The methoxy substituents also protect the selenium in the selenenic acid intermediates from overoxidation to seleninic acids or irreversible inactivation to selenonic acid derivatives. The additional substituents also play a crucial role in the selenenyl sulfide intermediates, by preventing thiol exchange reactions-which would normally lead to an inactivation pathway-at the selenium centers. The strengths of SeN interactions in the selenenyl sulfide intermediates are dramatically reduced upon introduction of the methoxy substituents, which not only reduce the thiol exchange reactions at selenium but also enhance the nucleophilic attack of the incoming thiols at sulfur. The facile attack of thiols at sulfur in the selenenyl sulfides also prevents the reactions between the selenenyl sulfides and H(2)O(2) that can regenerate the selenenic acids (reverse-GPx cycle). These studies reveal that the simple 6-OMe groups play multiple roles in each of the catalytically active intermediates by introducing steric and electronic effects that are required for efficient catalysis.     

Cyclic and stripping voltammetry of Se(+4) and Se(-2) at carbon electrodes in acid solutions

The behaviour of the Se(+4)?Se(0)?Se(?2) system was studied by cyclic and stripping voltammetry using several kinds of graphite and glassy carbon electrodes in the pH range from 0 to 8. Well-defined curves of Se(+4) reduction were obtained with a very soft graphite electrode, whereas poorly defined curves were recorded with glassy carbon electrodes. The reduction of Se(+4) in acid solution led to the formation of two forms of elemental selenium. One was formed in a direct electroreduction and the other in a subsequent chemical reaction between Se(+4) and Se(?2). These two forms of Se(0) gave separate reduction and oxidation peaks. Hydrogen selenide was anodically oxidized stepwise to elemental selenium and selenous acid. With an increase of pH the extent of Se(+4) reduction decreased and the extent of Se(?2) oxidation increased.The cathodic and anodic stripping peaks of elemental selenium cannot be used for the determination of traces of Se(+4) because they appear only in solutions with Se(+4) concentrations >1×10^?5 mol 1^?1.     

Formation of volatile selenium species in synthetic seawater under light and dark experimental conditions

Experiments were performed in the laboratory on synthetic seawater spiked with different selenium species at trace levels to study the formation of volatile selenium compounds under dark or controlled simulated sunlight conditions. Spiking the reaction media with inorganic and organic selenium compounds demonstrated that several volatile selenium species could be formed under these simulated conditions. Selenoamino acids react to produce significant amounts of volatile selenium species in both light and dark conditions. Products formed include dimethyl selenide (DMSe), dimethyl selenyl sulphide (DMSeS) and dimethyl diselenide (DMDSe). Inorganic selenium oxyanions added to the synthetic reaction media did not form volatile species via abiotic reactions despite the presence of strong methylating agents. These results suggest that the formation of stable volatile species from bio‐organic selenium compounds can occur via abiotic reactions in the marine photic zone. Copyright © 2000 John Wiley & Sons, Ltd.     

Reactions of triads Se8KOHDMSO,Se8KOHDMSO,TeKOHHMPA with acetylenes

A new general approach to anionic transformations of acetylenes using superbasic media has been developed. It allows series of new reactions which are not undergone by acetylene under conventional conditions. The triads Se₈KOHdimethylsulfoxide (DMSO), Se₈KOHDMSO, TeKOH-hexamethyl-phosphorictriamide (HMPA) are proposed as new effective reagents for the preparation of unsaturated compounds of sulfur, selenium and tellerium. A series of reactions of acetylene with sulfur, selenium and tellerium proceeding in DMSO or HMPA in the presence of alkali and water at 80–120° leading to divinyl sulfide, divinyl selenide and divinyl teluride in 25–80% yields have been found. Thiophen, di-1-(1,3-butadienyl) sulfide, 1-vinyl-2-thiabicyclo[3.2.0]hept-3-ene, and dihydrothiophen have been obtained by the reaction of vinylacetate with sulfur. The reaction of vinylacetylene with selenium affords selenophen, di-1-(1,3-butadienyl) selenide, 1-vinyl-2-selenabicyclo[3.2.0]hept-3-ene, methyl (1-(1,3-butadienyl) sulfide, and methylthiomethyl 1-(1,4-butadienyl) selenide, vinyl 1-(1,3-butadienyl) sulfide, and methylthiomethyl 1-(1,3-butadienyl) selenide (the latter two with DMSO participation). The reaction of vinylacetate with tellerium gives mainly di-1-(1,3-butadienyl) telluride. A series of reactions between DMSO and selenium leading to dimethyl sulfide, dimethyl sulfoselenide, and methylthiomethyl selenide have been observed.     

Reductive stripping chronopotentiometry for selenium in biological materials with a flow system

Reductive stripping chronopotentiometry in a flow system is used for determination of selenium in mussels and NBS bovine liver after acid digestion. The automated flow system contains a thin-layer cell with a mercury film electrode. In the deposition step, mercury(II) selenide is formed on the mercury film surface; the stripping step involves reduction to mercury and hydrogen selenide. This reduction is done in a separate solution of almost saturated calcium chloride, which eliminates interferences from oxygen so that solutions need not be deoxygenated. The detection limit is 0.14 μg l^?1 selenium at a deposition time of 120 s.     

Effect of substituents on the GPx-like activity of ebselen: steric versus electronic

The direct oxidation of ebselen and several derivatives by hydrogen peroxide is investigated using the B3LYP/6-31G(d,p) method to elucidate the effects of substituents on GPx-like activity. While previous studies have attributed the differences in GPx activity of substituted ebselen compounds to the electronic nature of the substituents, the influence of functional groups is poorly understood. The effects of various solvents are incorporated by employing the CPCM method. It is shown that a substituent in the ortho position to the selenium atom sterically hinders attack of a nucleophile at selenium and thus increases the barrier to reaction. The observed increase in GPx-like activity of an ebselen derivative with an ortho substituent is explained by the fact that the steric hindrance prevents thiol exchange reactions.     

Biomimetic studies on anti-thyroid drugs and thyroid hormone synthesis

The selenium analogues of anti-thyroid drugs exhibit their anti-thyroid action by a mechanism different from that of MMI. The selenium analogue of MMI and related selenium compounds exhibit high GPx activity, providing a novel method for the reversible inhibition of thyroid hormone biosynthesis.