Identification of [(GS)2AsSe]− in rabbit bile by size‐exclusion chromatography and simultaneous multielement‐specific detection by inductively coupled plasma atomic emission spectroscopy

An arsenic–selenium metabolite that exhibited the same arsenic and selenium X‐ray absorption near‐edge spectra as the synthetic seleno‐bis(S‐glutathionyl) arsinium ion [(GS)₂AsSe]^? was recently detected in rabbit bile within 25 min after intravenous injection of rabbits with sodium selenite and sodium arsenite. X‐ray absorption spectroscopy did not (and cannot) conclusively identify the sulfur‐donor in the in vivo sample. After similar treatment of rabbits, we analyzed the collected bile samples by size‐exclusion chromatography (SEC) using inductively coupled plasma atomic emission spectroscopy (ICP‐AES) to monitor arsenic, selenium and sulfur simultaneously. The bulk of arsenic and selenium eluted in a single peak, the intensity of which was greatly increased upon spiking of the bile samples with synthethic [(GS)₂AsSe]^?. Hence, we identify [(GS)₂AsSe]^? as the major metabolite in bile after exposure of rabbits to selenite and arsenite. The reported SEC–ICP‐AES method is the first chromatographic procedure to identify this biochemically important metabolite in biological fluids and is thus a true alternative to X‐ray absorption spectroscopy, which is not available to many chemists. Copyright © 2001 John Wiley & Sons, Ltd.     

Simultaneous arsenic‐ and selenium‐specific detection of the dimethyldiselenoarsinate anion by high‐performance liquid chromatography–inductively coupled plasma atomic emission spectrometry

The seleno‐bis (S‐glutathionyl) arsinium ion, [(GS)₂AsSe]^?, which can be synthesized from arsenite, selenite and glutathione (GSH) at physiological pH, fundamentally links the mammalian metabolism of arsenite with that of selenite and is potentially involved in the chronic toxicity/carcinogenicity of inorganic arsenic. A mammalian metabolite of inorganic arsenic, dimethylarsinic acid, reacts with selenite and GSH in a similar manner to form the dimethyldiselenoarsinate anion, [(CH₃)₂As(Se)₂]^?. Since dimethylarsinic acid is an environmentally abundant arsenic compound that could interfere with the mammalian metabolism of the essential trace element selenium via the in vivo formation of [(CH₃)₂As(Se)₂]^?, a chromatographic method was developed to rapidly identify this compound in aqueous samples. Using an inductively coupled plasma atomic emission spectrometer (ICP‐AES) as the simultaneous arsenic‐ and selenium‐specific detector, the chromatographic retention behaviour of [(CH₃)₂As(Se)₂]^? was investigated on styrene–divinylbenzene‐based high‐performance liquid chromatography (HPLC) columns. With a Hamilton PRP‐1 column as the stationary phase (250 × 4.1 mm ID, equipped with a guard column) and a phosphate‐buffered saline buffer (0.01 mol dm^?3, pH 7.4) as the mobile phase, [(CH₃)₂As(Se)₂]^? was identified in the column effluent according to its arsenic:selenium molar ratio of 1 : 2. With this stationary phase/mobile phase combination, [(CH₃)₂As(Se)₂]^? was baseline‐separated from arsenite, selenite, dimethylarsinate, methylarsonate and low molecular weight thiols (GSH, oxidized GSH) that are frequently encountered in biological samples. Thus, the HPLC–ICP‐AES method developed should be useful for rapid identification and quantification of [(CH₃)₂As(Se)₂]^? in biological fluids. Copyright © 2003 John Wiley & Sons, Ltd.     

Kinetics of the diazotization and azo coupling reactions of procaine in the micellar media

The kinetics of the diazotization reaction of procaine in the presence of anionic micelles of sodium dodecyl sulfate (SDS) and cationic micelles of cetyltrimethyl ammonium bromide (CTAB), dodecyltrimethyl ammonium bromide (DDTAB) and tetradecyltrimethyl ammonium bromide (TDTAB) were carried out spectrophotometrically at λ_max = 289 nm. The values of the pseudo first order rate constant were found to be linearly dependent upon the [NaNO₂] in the concentration range of 1.0 × 10⁻³ mol dm⁻³ to 12.0 × 10⁻³ mol dm⁻³ in the presence of 2.0 × 10⁻² mol dm⁻³ acetic acid. The concentration of procaine was kept constant at 6.50 × 10⁻⁵ mol dm⁻³. The addition of the cationic surfactants increased the reaction rate and gave plateau like curve. The addition of SDS micelles to the reactants initially increased the rate of reaction and gave maximum like curve. The maximum value of the rate constant was found to be 9.44 × 10⁻³ s⁻¹ at 2.00 × 10⁻³ mol dm⁻³ SDS concentration. The azo coupling of diazonium ion with β-naphthol (at λ_max = 488) nm was found to linearly dependent upon [ProcN₂⁺] in the presence of both the cationic micelles (CTAB, DDTAB and TDTAB) and anionic micelles (SDS). Both the cationic and anionic micelles inhibited the rate of reactions. The kinetic results in the presence of micelles are explained using the Berezin pseudophase model. This model was also used to determine the kinetic parameters e.g. k_m, K_s from the observed results of the variation of rate constant at different [surfactants].     

cyclo(‐Cha–Oxz–d‐Val–Thz–Ile–Oxz–d‐Val–Thz‐) N,N‐di­methyl­acetamide dihydrate: a square form of cyclo­hexyl­alanine‐incorporated ascidiacycl­amide having the strongest cytotoxicity

The title compound, 1‐cyclo­hexyl­methyl‐1‐de(1‐methyl­propyl)­asci­dia­cycl­amide N,N‐di­methyl­acet­amide di­hy­drate, C₃₉H₅₆N₈O₆S₂·C₄H₉NO·2H₂O, a cyclo­hexyl­alanine‐incorporated ascidiacycl­amide analogue ([Cha]ASC), shows a square form similar to natural ASC. On the other hand, CD (circular dichroism) spectra showed [Cha]ASC to have a folded structure in solution, making it the second known analogue to show a discrepancy between its crystal and solution structures. Moreover, the cytotoxicity of [Cha]ASC (ED₅₀ = 5.6 µg ml⁻¹) was approximately two times stronger than that of natural ASC or a related phenyl­alanine‐incorporated analogue, viz. cyclo(‐Phe–Oxz–d ‐Val–Thz–Ile–Oxz–d ‐Val–Thz‐) ([Phe]ASC), and was confirmed to be associated with the square form. However, [Phe]ASC was previously shown to be folded in the crystal structure, which suggests that the difference between the aromatic and aliphatic rings affects the molecular folding of the ASC mol­ecule.     

Hydrogen phosphate and dihydrogen phosphate salts of 4‐amino­azobenzene

4‐Amino‐trans‐azobenzene {or 4‐[(E)‐phenyl­diazen­yl]aniline} can form isomeric salts depending on the site of protonation. Both orange bis{4‐[(E)‐phenyl­diazen­yl]anilinium} hydrogen phos­phate, 2C₁₂H₁₂N₃⁺·HPO₄²⁻, and purple 4‐[(E)‐phenyl­diazen­yl]­anilinium dihydrogen phosphate phosphoric acid solvate, C₁₂H₁₂N₃⁺·H₂PO₄⁻·H₃PO₄, (II), have layered structures formed through O—H⋯O and N—H⋯O hydrogen bonds. Additionally, azobenzene fragments in (I) are assembled through C—H⋯π inter­actions and in (II) through π–π inter­actions. Arguments for the colour difference are tentatively proposed.     

Thia­mine tetra­phenyl­borate monohydrate: a two‐dimensional hydrogen‐bonded network with (4,4)‐topology

The title compound, 3‐[(4‐amino‐2‐methyl­pyrimidin‐5‐yl)­meth­yl]‐5‐(2‐hydroxy­eth­yl)‐4‐methyl­thia­zolium tetra­phenyl­borate monohydrate, C₁₂H₁₇N₄OS⁺·C₂₄H₂₀B⁻·H₂O, is a salt in which the thiamine cations are linked by hydrogen bonds into a two‐dimensional network having (4,4)‐topology. The stacked sheets form channels, which are occupied by the anions; the cations and anions are linked by C—H⋯π(arene) hydrogen bonds.     

Three‐dimensional hydrogen‐bonded framework structures in flunarizinium nicotinate and flunarizinediium bis(4‐toluenesulfonate) dihydrate

The structures of two salts of flunarizine, namely 1‐bis[(4‐fluorophenyl)methyl]‐4‐[(2E)‐3‐phenylprop‐2‐en‐1‐yl]piperazine, C₂₆H₂₆F₂N₂, are reported. In flunarizinium nicotinate {systematic name: 4‐bis[(4‐fluorophenyl)methyl]‐1‐[(2E)‐3‐phenylprop‐2‐en‐1‐yl]piperazin‐1‐ium pyridine‐3‐carboxylate}, C₂₆H₂₇F₂N₂⁺·C₆H₄NO₂⁻, (I), the two ionic components are linked by a short charge‐assisted N—H...O hydrogen bond. The ion pairs are linked into a three‐dimensional framework structure by three independent C—H...O hydrogen bonds, augmented by C—H...π(arene) hydrogen bonds and an aromatic π–π stacking interaction. In flunarizinediium bis(4‐toluenesulfonate) dihydrate {systematic name: 1‐[bis(4‐fluorophenyl)methyl]‐4‐[(2E)‐3‐phenylprop‐2‐en‐1‐yl]piperazine‐1,4‐diium bis(4‐methylbenzenesulfonate) dihydrate}, C₂₆H₂₈F₂N₂²⁺·2C₇H₇O₃S⁻·2H₂O, (II), one of the anions is disordered over two sites with occupancies of 0.832 (6) and 0.168 (6). The five independent components are linked into ribbons by two independent N—H...O hydrogen bonds and four independent O—H...O hydrogen bonds, and these ribbons are linked to form a three‐dimensional framework by two independent C—H...O hydrogen bonds, but C—H...π(arene) hydrogen bonds and aromatic π–π stacking interactions are absent from the structure of (II). Comparisons are made with some related structures.     

Review: Reactive selenium metabolites as targets of toxic metals/metalloids in mammals: a molecular toxicological perspective

Human activities have been contaminating the environment with toxic heavy metal and metalloid compounds. Since the toxicity of one metal or metalloid can be dramatically modulated by the simultaneous ingestion of another, studies addressing the molecular basis of chemical interactions between toxic and essential elements are increasingly important. The intravenous injection of rabbits with selenite and arsenite or with selenite and mercuric mercury resulted in the in vivo formation of the seleno‐bis (S‐glutathionyl) arsinium ion, [(GS)₂AsSe]^?, or a glutathione‐coated mercuric selenide, (GS)₅(HgSe)_core, in blood. The formation of these species (and the formation of a cadmium–selenium species in blood after the exposure of rats to selenite and cadmium) critically involves reactive selenite metabolites, such as GS–Se^? and/or HSe^?, which indicates that these physiologically important metabolites are molecular targets of ingested toxic metals and metalloids. The fate and stability of [(GS)₂AsSe]^? and (GS)₅(HgSe)_core in vivo imply that the chronic exposure of mammals to inorganic arsenic and mercury will cumulatively affect the bioavailability of selenium, which could lead to selenium deficiency. Since selenium deficiency is significantly associated with the etiology of cancer in humans, the GSH‐driven in vivo formation of selenium‐containing metal and metalloid species provides a likely molecular mechanism for the chronic toxicity of environmentally persistent inorganic arsenic, mercury and cadmium. Copyright © 2002 John Wiley & Sons, Ltd.     

Mono­alkyl­ated 4′‐aryl‐substituted terpyridines

1‐Methyl‐2‐[4‐phenyl‐6‐(pyridinium‐2‐yl)­pyridin‐2‐yl]­pyridinium diperchlorate, C₂₂H₁₉N₃²⁺·2ClO₄⁻, (I), and 2‐[4‐(methoxy­phenyl)‐2,2′‐bipyridin‐6‐yl]‐1‐methyl­pyridinium iodide, C₂₃H₂₀N₃O⁺·I⁻, (II), both crystallize in the monoclinic space group P2₁/c. In contrast with the monocharged mol­ecule of (II), the doubly charged mol­ecule of (I) contains an additional protonated pyridine ring. One of the two perchlorate counter‐anions of (I) interacts with the cation of (I) via an N—H⋯O hydrogen bond. In (II), two mol­ecules related by a centre of symmetry are connected by weak π–π interactions, forming dimers in the crystal structure.     

One-electron oxidation of glutathione by azide radicals in neutral medium: A gamma and pulse radiolysis study

The selective interactions of azide radicals with glutathione (GSH) have been quantitatively studied in buffered neutral aqueous solutions using γ and pulse radiolysis. The sulfur centered GS̽ and GSSG⨪ radicals are produced in pulse and γ radiolysis. Kinetic experiments and simulation allowed to estimate the rate constant of N̽₃ with GSH which has been found to be equal to (9.5 ± 0.5) × 10⁶M⁻¹ s⁻¹ at pH 7. In steady state radiolysis, we have found GSSG as the final product formed with an initial G value of 2.9 × 10⁻⁷ mol J⁻¹.     

(Z)‐2‐Methylbuten‐1‐yl(aryl)iodonium trifluoromethanesulfonates containing electron‐withdrawing groups on the aryl moiety

The crystal structures of [(Z)‐2‐methyl­but‐1‐en‐1‐yl]­[4‐(tri­fluoro­methyl)­phenyl]­iodo­nium tri­fluoro­methane­sulfonate, C₁₂H₁₃F₃I⁺·CF₃O₃S^?, (I), (3,5‐di­chloro­phenyl)­[(Z)‐2‐methyl­but‐1‐en‐1‐yl]­iodo­nium tri­fluoro­methane­sulfonate, C₁₁H₁₂­Cl₂I⁺·CF₃O₃S^?, (II), and bis{[3,5‐bis­(tri­fluoro­methyl)­phenyl][(Z)‐2‐methyl­but‐1‐en‐1‐yl]­iodo­nium} bis­(tri­fluoro­methane­sulfonate) di­chloro­methane solvate, 2C₁₃H₁₂F₆I⁺·­2CF₃­O₃S^?·CH₂Cl₂, (III), are described. Neither simple acyclic β,β‐di­alkyl‐substituted alkenyl­(aryl)­idonium salts nor a series containing electron‐deficient aryl rings have been described prior to this work. Compounds (I)–(III) were found to have distorted square‐planar geometries, with each I atom interacting with two tri­fluoro­methane­sulfonate counter‐ions.     

Moxifloxacinium chloride–water–methanol (2/1/1), a novel anti­bacterial agent

Moxifloxacin, a novel fluoro­quinolone with a broad spectrum of anti­bacterial activity, is available as the solvated monohydro­chloride salt 7‐[(S,S)‐2‐aza‐8‐azoniabicyclo­[4.3.0]non‐8‐yl]‐1‐cyclo­propyl‐6‐fluoro‐8‐meth­oxy‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylic acid chloride–water–methanol (2/1/1), C₂₁H₂₅FN₃O₄⁺·Cl⁻·0.5H₂O·0.5CH₃OH. The asymmetric unit contains two cations, two chloride ions, a mol­ecule of water and one methanol mol­ecule. The two cations adopt conformations that differ by an almost 180° rotation with respect to the piperidinopyrrolidine side chain. The cyclo­propyl ring and the meth­oxy group are not coplanar with the quinoline ring system. The carboxylic acid function, the protonated terminal piperidyl N atom, the water mol­ecule, the chloride ion and the methanol mol­ecule participate in O—H⋯O, O—H⋯Cl, N—H⋯O and N—H⋯Cl hydrogen bonding, linking the mol­ecules into extended two‐dimensional networks.     

Self‐assembled hydrogen‐bonded bilayers in 1,4‐diazabicyclo[2.2.2]octane–N‐(phosphonomethyl)iminodiacetic acid–water (1/1/1.5)

The title compound is a hydrated salt, 1,4‐diazo­nia­bi­cyclo­[2.2.2]­octane–N‐[(hydroxy­phosphinato)­methyl]­iminiodi­acetate–water (1/1/1.5), C₆H₁₄N₂²⁺·C₅H₈NO₇P^2?·1.5H₂O, in which one of the water mol­ecules lies across a twofold rotation axis in space group P2/n. The ionic components are linked into sheets by a combination of a three‐centre N—H?(O)₂ hydrogen bond and two‐centre O—H?O and N—H?O hydrogen bonds, and these sheets are pairwise linked by the water mol­ecules into bilayers, by means of further O—H?O hydrogen bonds.     

Solvation effect in the thermal decomposition of 2,2′‐azoisobutyronitrile in the three‐component system

The thermal decomposition rate constant (k_d ) of 2,2′‐azoisobutyronitrile in acrylonitrile (AN; monomer A)–methyl methacrylate (MM; monomer B) comonomer mixtures in N,N‐dimethylformamide (DMF) as a function of the comonomer mixture composition and its concentration in the solvent at 60 °C was studied. The dependences k_d = f(x_A ,C) [x_A (mole fraction of A in the comonomer mixture) = A/(A + B) = A/C, where C is the comonomer mixture concentration] have a different course as a function of C: from a curve k_d = f(x_A ) approaching the straight line (C = 2 mol · dm⁻³) to a convex curve possessing a maximum at a point x_A = 0.7 (C = 4 mol · dm⁻³) to a curve with a flattened wide maximum within the range of x_A = 0.2–0.8 (C = 7 mol · dm⁻³) to a curve with the shape of a lying s (C = 9 mol · dm⁻³). All the courses of the experimental dependences k_d = f(x_A ,C) can be explained with a hypothesis of initiator solvation by the comonomers AN and MM and the solvent DMF. The existing solvated forms, their relative stability constants, the thermal decomposition rate constants, and the relative contents in the system were determined. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2156–2166, 2000     

Hydro­gen bonding in calcium–tri­fluoro­methane­sulfonate–1,3‐di‐4‐pyridyl­urea–methanol (1/2/2/4)

The structure of the supramolecular complex calcium–tri­fluoro­methane­sulfonate–1,3‐di‐4‐pyridyl­urea–methanol (1/2/2/4), Ca²⁺·2CF₃SO₃⁻·2C₁₁H₁₀N₄O·4CH₄O, is presented. The Ca²⁺ ion lies on an inversion centre and is octahedrally coordinated by four methanol mol­ecules and two tri­fluoro­methane­sulfonate counter‐ions. The molecular packing is dominated by hydrogen‐bonded sheets in the (110) plane which contain R(32) rings; in these rings, significant π–π interactions are observed between inversion‐related 1,3‐di‐4‐pyridyl­urea mol­ecules.     

Immunotoxicity of Organic Arsenic Compounds in Marine Animals

In the present study, we demonstrated for the first time the immunotoxic effects of organic arsenic compounds in marine animals, namely arsenocholine [AsCho; trimethyl(2-hydroxyethyl)arsonium cation], arsenobetaine [AsBe; the trimethyl(carboxymethyl)arsonium zwitterion] and the tetramethylarsonium ion (TetMA), to murine principal immune effector cells (macrophages and lymphocytes), comparing them with the effects of inorganic arsenicals in vitro . Inorganic arsenicals (arsenite and arsenate) showed strong cytotoxicity to both macrophages and lymphocytes. The concentration of arsenite that reduced the number of surviving cells to 50% of that in untreated controls (IC₅₀) was 3–5 μmol dm⁻³, and the cytotoxicity of arsenate (IC₅₀=100 μ-1 m mol dm⁻³) was lower than that of arsenite. Compared with these findings, trimethylarsenic compounds in marine animals, AsCho and AsBe, were less toxic even at a concentration over 10 mmol dm⁻³ to both macrophages and lymphocytes; however, TetMA had weak, but significant, cytotoxicity to these cells (IC₅₀ was about 6 mmol dm⁻³).     

l‐Methioninium chloride and l‐seleno­methioninium chloride at 103 K

The crystal structures of the title compounds, (S)‐1‐carboxy‐3‐(methyl­sulfanyl)­propanaminium chloride, C₅H₁₂NO₂S⁺·Cl⁻, and (S)‐1‐carboxy‐3‐(methyl­selanyl)­propanaminium chloride, C₅H₁₂NO₂Se⁺·Cl⁻, are isomorphous. The proton­ated l ‐methionine and l ‐seleno­methionine mol­ecules have almost identical conformations and create very similar contacts with the Cl⁻ anions in the crystal structures of both compounds. The amino acid cations and the Cl⁻ anions are linked viaN—H⋯Cl⁻ and O—H⋯Cl⁻ hydrogen bonds.     

Intramolecular cyclization of 4,7‐bis(2‐bromo­acetyl)‐1‐thia‐4,7‐di­azacyclo­nonane

The reaction of 1‐thia‐4,7‐di­azacyclo­nonane with bromo­acetyl bromide in CHCl₃ affords the unexpected salt 4‐(2‐bromo­acetyl)‐8‐oxo‐1‐thionia‐4,7‐di­aza­bi­cyclo­[5.2.2]­un­decane bromide, C₁₀H₁₆BrN₂O₂S⁺·Br⁻. Two units of the salt are linked by S⋯Br contacts about a crystallographic inversion centre, thus forming dimers that are linked by Br⋯Br contacts into extended ribbons. S⋯O contacts between these ribbons generate a two‐dimensional sheet.     

A novel one‐dimensional complex: catena‐poly­[[manganese(III)‐di‐μ‐2‐[(2‐hydroxy­ethyl)­imino­methyl]­phenolato‐κ2O1,N:κO2;κO2:κ2O1] chloride]

In the title one‐dimensional complex, {[Mn^III(C₉H₁₀NO₂)₂]Cl}_n, the Schiff base ligand 2‐[(2‐hydroxy­ethyl)­imino­methyl]­phenolate (Hsae⁻) functions as both a bridging and a chelating ligand. The Mn^III ion is six‐coordinated by two N and four O atoms from four different Hsae⁻ ligands, yielding a distorted MnO₄N₂ octahedral environment. Each [Mn^III(Hsae)₂]⁺ cationic unit has the Mn atom on an inversion centre and each [Mn^III(Hsae)₂]⁺ cation lies about another inversion centre. The chain‐like complex is further extended into a three‐dimensional network structure through Cl⋯H—O hydrogen bonds and C—H⋯π contacts involving the Hsae⁻ rings.     

A mixed‐valence manganese(III)–manganese(IV) di‐μ‐oxo complex, [(cyclam)MnO]2(ClO4)2(NO3)

The title dinuclear di‐μ‐oxo‐bis­[(1,4,8,11‐tetra­aza­cyclo­tetra­decane‐κ⁴N)­manganese(III,IV)] diperchlorate nitrate complex, [Mn₂O₂(C₁₀H₂₄N₄)₂](ClO₄)₂(NO₃) or [(cyclam)Mn­O]₂(ClO₄)₂(NO₃), was self‐assembled by the reaction of Mn²⁺ with 1,4,8,11‐tetra­aza­cyclo­tetra­decane in aqueous media. The structure of this compound consists of a centrosymmetric binuclear [(cyclam)MnO]³⁺ unit, two perchlorate anions and one nitrate anion. While the low‐temperature electron paramagnetic resonance spectra show a typical 16‐line signal for a di‐μ‐oxo Mn^III/Mn^IV dimer, the magnetic susceptibility studies also confirm a characteristic antiferromagnetic coupling between the electronic spins of the Mn^IV and Mn^III ions.