Selenium Analogues Research Articles

Synthesis and crystal structure of Fe[(Te1.5Se0.5)O5]Cl, the first iron compound with selenate(IV) and tellurate(IV) groups

During the search for selenium analogues of FeTe2O5Cl, the new iron (III) tellurate(IV) selenate(IV) chloride with the composition Fe[(Te1.5Se0.5)O5]Cl was synthesized by chemical vapor transport (CVT) reaction and characterized by TGA-, EDX-,SCXRD-analysis, as well as IR and Raman spectroscopy. It was found that Fe[(Te1.5Se0.5)O5]Cl crystallizes in the monoclinic space group P21/c with unitcell parameters a = 5.183(3) Å, b = 15.521(9) Å, c = 7.128(5) Å and β = 107.16(1)°. The crystal structure of Fe[(Te1.5Se0.5)O5]Cl represents a new structure type and contains electroneutral heteropolyhedral layers formed by dimers of the [FeO5Cl]8– octahedra, linked via common O-O edges, and mixed [Te3SeO10]4- tetramers. Adjacent layers are stacked along the b axis and linked by weak residual bonds. The new compound is stable up to 420 °C. DFT calculations predict Fe[(Te1.5Se0.5)O5]Cl to be a wide-gap semiconductor with the band gap of ca. 2.7 eV.

Selenoglutathione Diselenide: Unique Redox Reactions in the GPx-Like Catalytic Cycle and Repairing of Disulfide Bonds in Scrambled Protein.

Selenoglutathione (GSeH) is a selenium analogue of naturally abundant glutathione (GSH). In this study, this water-soluble small tripeptide was synthesized in a high yield (up to 98%) as an oxidized diselenide form, i.e., GSeSeG (1), by liquid-phase peptide synthesis (LPPS). Obtained 1 was applied to the investigation of the glutathione peroxidase (GPx)-like catalytic cycle. The important intermediates, i.e., GSe- and GSeSG, besides GSeO2H were characterized by 77Se NMR spectroscopy. Thiol exchange of GSeSG with various thiols, such as cysteine and dithiothreitol, was found to promote the conversion to GSe- significantly. In addition, disproportionation of GSeSR to 1 and RSSR, which would be initiated by heterolytic cleavage of the Se-S bond and catalyzed by the generated selenolate, was observed. On the basis of these redox behaviors, it was proposed that the heterolytic cleavage of the Se-S bond can be facilitated by the interaction between the Se atom and an amino or aromatic group, which is present at the GPx active site. On the other hand, when a catalytic amount of 1 was reacted with scrambled 4S species of RNase A in the presence of NADPH and glutathione reductase, native protein was efficiently regenerated, suggesting a potential use of 1 to repair misfolded proteins through reduction of the non-native SS bonds.

N‐Heterocyclic Carbene Adducts of Phenyldioxophosphorane and Its Heavier Sulfur and Selenium Analogues

The reactions of the N‐heterocyclic carbene–phenylphosphinidene adducts (NHC)PPh with dioxygen, elemental sulfur or selenium are reported. For NHC = 1,3,4,5‐tetramethylimidazolin‐2‐ylidene (IMe), the corresponding complexes (IMe)PE2Ph of phenyldioxophosphorane (PhPO2), phenyldithioxophosphorane (PhPS2) and phenyldiselenoxophosphorane (PhPSe2) were isolated and fully characterised, including determination of their molecular structures by single‐crystal X‐ray diffraction analyses. For the adducts of the sterically more demanding carbenes 1,3‐bis(2,4,6‐trimethylphenyl)imidazolin‐2‐ylidene (IMes) and 1,3‐bis(2,6‐diisopropylphenyl)imidazolin‐2‐ylidene (IPr), the reactions with dioxygen afforded the phenyldioxophosphorane complexes (IMes)PO2Ph and (IPr)PO2Ph, and their X‐ray diffraction crystal structures were established. In contrast, their reactions with sulfur and selenium resulted in the cleavage of the NHC–phosphorus bond and the formation of 2,4‐diphenyl‐2,4‐dithioxo‐1,3,2,4‐dithiadiphosphetane, (PhPS2)2, and 2,4‐diphenyl‐2,4‐diselenoxo‐1,3,2,4‐diselenadiphosphetane, (PhPSe2)2 (Woollins' reagent).

A comprehensive study of magnetic exchanges in the layered oxychalcogenides Sr3Fe2O5Cu2Q2 (Q = S, Se)

The layered oxysulfide Sr3Fe2O5Cu2S2 was prepared, and its crystal structure and magnetic properties were characterized by synchrotron X-ray diffraction (XRD), powder neutron diffraction (PND), Mössbauer spectroscopy measurements and by density functional theory (DFT) calculations. In addition, the spin exchange interactions leading to the ordered magnetic structure of Sr3Fe2O5Cu2S2 were compared with those of its selenium analogue Sr3Fe2O5Cu2Se2. The oxysulfide Sr3Fe2O5Cu2S2 adopts a G-type antiferromagnetic (AFM) structure at a temperature in the range 485–512K, which is comparable with the three-dimensional (3D) AFM ordering temperature, TN≈490K, found for Sr3Fe2O5Cu2Se2. Consistent with this observation, the spin exchange interactions of the magnetic (Sr3Fe2O5)2+ layers are slightly greater (but comparable) for oxysulfide than for the oxyselenide. Attempts to reduce or oxidize Sr3Fe2O5Cu2S2 using topochemical routes yield metallic Fe.

Structural analysis and antimicrobial activity of 2[1H]-pyrimidinethione/selenone derivatives

Four new crystal structures of sulfur and selenium analogues of 2[1H]-pyrimidinone derivatives were determined with the use of X-ray diffraction method. The molecular geometry and intermolecular interactions of the investigated molecules were analyzed in order to find the structural features and geometrical parameters, which can be responsible for antimicrobial activities. The influence of chalcogen substituents (sulfur and selenium) on the crystal packing was also studied. The main differences in the molecular structures exist in mutual arrangement of two aromatic rings. The intermolecular interactions in all investigated compounds are similar. Furthermore, the in vitro antibacterial and antifungal activities for these compounds were evaluated. Preliminary investigations have identified two highly potent antibacterial compounds containing selenium atom, which display selectivity towards staphylococci and micrococci. This selectivity was not observed for a control compound used as a drug, namely vancomycin. These compounds possess also good antifungal activity. This is the first report of biological activities of 2[1H]-pyrimidineselenone derivatives.

Assessing the dispersive and electrostatic components of the selenium-aromatic interaction energy by DFT.

Selenium has been increasingly recognized as an important element in biological systems, which participates in numerous biochemical processes in organisms, notably in enzyme reactions. Selenium can substitute sulfur of cysteine and methionine to form their selenium analogues, selenocysteine (Sec) and selenomethionine (SeM). The nature of amino acid pockets in proteins is dependent on their composition and thus different non-covalent forces determine the interactions between selenium of Sec or SeM and other functional groups, resulting in specific biophysical behavior. The discrimination of selenium toward sulfur has been reported. In order to elucidate the difference between the nature of S-π and Se-π interactions, we performed extensive DFT calculations of dispersive and electrostatic contributions of Se-π interactions in substituted benzenes/hydrogen selenide (H2Se) complexes. The results are compared with our earlier reported S-π calculations, as well as with available experimental data. Our results show a larger contribution of dispersive interactions in Se-π systems than in S-π ones, which mainly originate from the attraction between Se and substituent groups. We found that selenium exhibits a strong interaction with aromatic systems and may thus play a significant role in stabilizing protein folds and protein-inhibitor complexes. Our findings can also provide molecular insights for understanding enzymatic specificity discrimination between single selenium versus a sulfur atom, notwithstanding their very similar chemical properties.

Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue.

Synthetic insulin analogues with a long lifetime are current drug targets for the therapy of diabetic patients. The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin-degrading enzyme (IDE) without impairing the hormonal function. The [C7UA ,C7UB ] variant of bovine pancreatic insulin (BPIns) was successfully prepared by using two selenocysteine peptides (i.e., the C7U analogues of A- and B-chains, respectively). In a buffer solution at pH 10 they spontaneously assembled under thermodynamic control to the correct insulin fold. The selenoinsulin (Se-Ins) exhibited a bioactivity comparable to that of BPIns. Interestingly, degradation of Se-Ins with IDE was significantly decelerated (τ1/2 ≈8 h vs. ≈1 h for BPIns). The lifetime enhancement could be due to both the intrinsic stability of the diselenide bond and local conformational changes induced by the substitution.

2,4-Ditellurouracil and its 5-fluoro derivative: Theoretical investigations of structural, energetics and ADME parameters

2,4-Ditellurouracil exhibits keto-enol tautomerism via different pathways resulting in seven tautomers. These pathways were studied in the gas phase using density functional theory method. The functionals used were BLYP, B3LYP and BHLYP and the basis sets were 6–311++G(d,p) for all atoms except that LanL2DZ ECP was used for tellurium atom only. The results indicate that the diketo form is more stable as observed for uracil and its sulfur and selenium analogues. The effect of introducing fluorine at position 5 was also investigated and the energy difference between the diketo and dienol forms is reduced. 2,4-Ditellurouracil and its 5-fluoro analogue are expected to exist exclusively as the diketo form due to the high interconversion energy barrier. We extended the investigation to predict ADME parameters of the most stable diketo and dienol tautomers in view of understanding their biological properties. This research enlightens keto-enol tautomerism of 2,4-ditellurouracil and its 5-fluoro derivative with additional insights to biological functions.

Comparison of the redox chemistry of sulfur- and selenium-containing analogs of uracil

Selenium is present in proteins in the form of selenocysteine, where this amino acid serves catalytic oxidoreductase functions. The use of selenocysteine in nature is strongly associated with redox catalysis. However, selenium is also found in a 2-selenouridine moiety at the wobble position of tRNAGlu, tRNAGln and tRNALys. It is thought that the modifications of the wobble position of the tRNA improves the selectivity of the codon-anticodon pair as a result of the physico-chemical changes that result from substitution of sulfur and selenium for oxygen. Both selenocysteine and 2-selenouridine have widespread analogs, cysteine and thiouridine, where sulfur is used instead. To examine the role of selenium in 2-selenouridine, we comparatively analyzed the oxidation reactions of sulfur-containing 2-thiouracil-5-carboxylic acid (s2c5Ura) and its selenium analog 2-selenouracil-5-carboxylic acid (se2c5Ura) using 1H-NMR spectroscopy, 77Se-NMR spectroscopy, and liquid chromatography-mass spectrometry. Treatment of s2c5Ura with hydrogen peroxide led to oxidized intermediates, followed by irreversible desulfurization to form uracil-5-carboxylic acid (c5Ura). In contrast, se2c5Ura oxidation resulted in a diselenide intermediate, followed by conversion to the seleninic acid, both of which could be readily reduced by ascorbate and glutathione. Glutathione and ascorbate only minimally prevented desulfurization of s2c5Ura, whereas very little deselenization of se2c5Ura occurred in the presence of the same antioxidants. In addition, se2c5Ura but not s2c5Ura showed glutathione peroxidase activity, further suggesting that oxidation of se2c5Ura is readily reversible, while oxidation of s2c5Ura is not. The results of the study of these model nucleobases suggest that the use of 2-selenouridine is related to resistance to oxidative inactivation that otherwise characterizes 2-thiouridine. As the use of selenocysteine in proteins also confers resistance to oxidation, our findings suggest a common mechanism for the use of selenium in biology.

Crystal Structure and Thermoelectric Properties of the 7,7L Lillianite Homologue Pb6Bi2Se9.

Pb6Bi2Se9, the selenium analogue of heyrovsyite, crystallizes in the orthorhombic space group Cmcm (#63) with a = 4.257(1) Å, b = 14.105(3) Å, and c = 32.412(7) Å at 300 K. Its crystal structure consists of two NaCl-type layers, A and B, with equal thickness, N1 = N2 = 7, where N is the number of edge-sharing [Pb/Bi]Se6 octahedra along the central diagonal. In the crystal structure, adjacent layers are arranged along the c-axis such that bridging bicapped trigonal prisms, PbSe8, are located on a pseudomirror plane parallel to (001). Therefore, Pb6Bi2Se9 corresponds to a 7,7L member of the lillianite homologous series. Electronic transport measurements indicate that the compound is a heavily doped narrow band gap n-type semiconductor, with electrical conductivity and thermopower values of 350 S/cm and -53 μV/K at 300 K. Interestingly, the compound exhibits a moderately low thermal conductivity, ∼1.1 W/mK, in the whole temperature range, owing to its complex crystal structure, which enables strong phonon scattering at the twin boundaries between adjacent NaCl-type layers A and B. The dimensionless figure of merit, ZT, increases with temperature to 0.25 at 673 K.

The Association between the Urinary Excretion of Trimethylselenonium and Trimethylsulfonium in Humans.

Hydrogen sulfide is a signaling molecule that plays important roles in several physiological processes, and its methylation product trimethylsulfonium (TMS) is a natural constituent of human urine that could serve as a biomarker for hydrogen sulfide. In vitro studies showed that the enzyme indole-ethylamine N-methyltransferase (INMT) is responsible for the production of trimethylsulfonium as well as its selenium analogue trimethylselenonium (TMSe). Marked inter-individual variability in TMSe production is associated with genetic polymorphisms in the INMT gene, but it remains unclear whether these polymorphisms affect substrate specificity or general enzymatic activity. Therefore, we explore the association between the TMS and TMSe production phenotypes. Caucasian volunteers were recruited and grouped according to their TMSe status into “TMSe producers” and “TMSe non-producers”, and morning urine samples were collected over 5 consecutive days from each volunteer. A total of 125 urine samples collected from 25 volunteers (13 TMSe producers and 12 TMSe non-producers) were analyzed for total selenium and total sulfur using inductively coupled plasma mass spectrometry (ICPMS), trimethylselenonium using HPLC/ICPMS, and trimethylsulfonium using HPLC/electrospray ionization—triple quadrupole—mass spectrometry (ESI-QQQ-MS). Although there was no correlation between TMS and TMSe urinary levels within the “TMSe producers” group, the “TMSe producers” had urinary levels of TMS 10-fold higher than those of the “TMSe non-producers” (P < 0.001). This result indicates that stratification according to TMSe status or genotype is crucial for the correct interpretation of urinary TMS as a possible biomarker for hydrogen sulfide body pools.

Experimental and theoretical studies of new rhenium carbonyls containing 4,5-bis(chalcogenodiphenylphosphinoyl)-1,2,3-triazolates

The novel binuclear complexes [Re(CO)3-μ-{κ3-N,N′,E-LT-E2}2]2 E = S and Se were prepared upon reaction of the corresponding potassium bis(chalcogenodiphenylphosphinoyl)triazolate, K[LT−E2], and [ReBr(CO)5]. 31P{1H}-NMR monitoring studies showed that formation of the binuclear complexes was preceded by the corresponding mononuclear complex [Re(CO)4{κ2-N,E-LT-E2] (E = S, Se). Theoretical calculations indicated that a faster reaction time for the formation of the sulfur binuclear complex in comparison with its selenium analog stems from thermodynamic considerations. The new complexes herein reported were characterized by standard spectroscopic techniques and single crystal X-ray analysis.

Synthesis and structure of new 3,7-diazabicyclo[3.3.1]nonane derivatives

Aminomethylation of triethylammonium 4-aryl-3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridin-2-olates and their sulfur and selenium analogs, as well as the structure of formed products, were studied in details. The reaction is of general character and leads to the formation of 7-substituted 9-aryl-2,4-dioxo-, 9-aryl-4-oxo-2-thioxo-, 9-aryl-4-oxo-2-selenoxo-3,7-diazabicyclo[3.3.1]nonane derivatives or their salts. The structures of ethyl 9-(2-chlorophenyl)-5-cyano-7-(4-methylphenyl)-2-oxo-4-thioxo-3,7-diazabicyclo[3.3.1]nonane-1-carboxylate (as a complex with N-methylmorpholine) and triethylammonium salt of 7-benzyl-4-oxo-2-selenoxo-9-(2-thienyl)-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarbonitrile were studied by X-ray crystallography.

Internal Rotation of 2-, 3- and 4-Pyridine Carboxaldehydes and Their Chalcogen Analogues (S and Se) in the Gas and Solution Phases: A Theoretical Investigation

The optimized molecular structures, vibrational wavenumbers and corresponding vibrational assignments of the syn and anti conformers of 2-, 3- and 4-pyridine carboxaldehydes and their sulfur and selenium analogues were calculated using the density functional theory method employing the B3LYP functional with the 6-311++G(d,p) basis set and second order Moller–Plesset Perturbation Theory (MP2) method with the cc-pVDZ basis set. The calculations were adapted to the C s symmetries of all ground state structures. The transition state arising from syn-anti isomerization was also modelled. All structures were fully optimized, and the geometries, rotational constants, dipole moments, charges, thermodynamic properties and energies are reported. Energies of the optimized structures were used to obtain the energy difference between the syn and anti conformers and the rotational barrier. The calculated vibrational wavenumbers were appropriately assigned to the various fundamental modes of vibrations. The Integral Equation Formalism Polarization Continuum Model was used to calculate the optimized geometry and the vibrational wavenumbers for all of the compounds in nine solvents: heptane, chloroform, tetrahydrofuran, dichloroethane, acetone, ethanol, methanol, dimethylsulfoxide and water. In addition, the LUMO, HOMO and energy band gap are also reported. The results indicate that the anti conformer is preferred with a rotational barrier of at least 19 kJ·mol−1.

Selenium analogs of raloxifene: antioxidant activity endowed to an old drug

The antioxidant activity of selenium-containing analogs of raloxifene was studied by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl, superoxide, nitric oxide, and peroxyl radicals. These compounds exhibited similar scavenging properties as resveratrol with respect to superoxide radical and had an impressive activity in peroxyl radical scavenging, making them promising candidates for the development of antioxidant agents.

ChemInform Abstract: Selenium Analogues of (S)‐Clopidogrel: Preparation Method and Properties.

AbstractA new and simple approach to synthesize selenium analogues of clopidogrel [ct.

Theoretical investigation on the crystal structures and electron transfer properties of cyanated TTPO and their selenium analogs

We designed a series of 5,6,7-trithiapentacene-13-one (TTPO) derivatives (from 1 to 20) by attaching cyano groups (–CN) and by replacing S atoms with Se. The incoherent charge-hopping model combined with the Marcus–Hush electron transfer theory were used to evaluate the charge mobility of the title compounds as potential n-type organic field-effect transistors (OFETs) candidates. Based on the optimized face-to-face dimers, the crystal structures were predicted. The replacement of S with Se can decrease the electron reorganization energy (λ –). The introduction of −CN can decrease the energy levels of both HOMOs and LUMOs, which increases the stability. According to the electronic affinities (EA) and structures of dimers predicted by the DFT method coupled with dispersion corrections (−D), we selected compounds 2, 14, 15, and 19 as initial well-performance OFETs materials and predicted their crystal structures. Based on the optimized crystal structures, the charge (both electron and hole) transport mobilities are estimated. Electron mobilities of 14 and 15 are as high as 2.32 and 2.48 cm2 V−1 s−1, respectively, indicating that 14 and 15 are the promising n-type OFETs materials. What’s more, the predicted crystals show remarkable anisotropic charge mobilities. The maximum electron mobility appears along the direction of face-to-face π-stacking.

Accelerating chemoselective peptide bond formation using bis(2-selenylethyl)amido peptide selenoester surrogates.

Given the potential of peptide selenoesters for protein total synthesis and the paucity of methods for the synthesis of these sensitive peptide derivatives, we sought to explore the usefulness of the bis(2-selenylethyl)amido (SeEA) group, i.e. the selenium analog of the bis(2-sulfanylethyl)amido (SEA) group, for accelerating peptide bond formation. A chemoselective exchange process operating in water was devised for converting SEA peptides into the SeEA ones. Kinetic studies show that SeEA ligation, which relies on an initial N,Se-acyl shift process, proceeds significantly faster than SEA ligation. This property enabled the design of a kinetically controlled three peptide segment assembly process based on the sequential use of SeEA and SEA ligation reactions. The method was validated by the total synthesis of hepatocyte growth factor K1 (85 AA) and biotinylated NK1 (180 AA) domains.

The synthesis, molecular structure and spectra properties of sulphur and selenium deferiprone analogues

Deferiprone has a broad spectrum of biological effects. Thus it is interesting to investigate the influence of structural changes in deferiprone on its biological activity. This work presents a synthesis of a new selenium analogue of deferiprone, 3-hydroxy-1,2-dimethyl-4(1H)- pyridineselenone (3-HDPSe), and an improved method for synthesis of a sulfur analogue of deferiprone, 3-hydroxy-1,2-dimethyl-4(1H)-pyridinethione (3-HDPT). The structures of the synthesized compounds were confirmed by means of IR, MS, 1 H NMR and 13 C NMR measurements. Single crystals of the selenium analogue were obtained and the crystal structure determined using X-ray diffraction. Additionally DFT (the B3LYP functional combined with the 6-311++G** basis set) theoretical calculations were conducted and the results compared with experimental data.

Modulation of a Molecular π-Electron System in a Purely Organic Conductor that Shows Hydrogen-Bond-Dynamics-Based Switching of Conductivity and Magnetism.

New important aspects of the hydrogen-bond (H-bond)-dynamics-based switching of electrical conductivity and magnetism in an H-bonded, purely organic conductor crystal have been discovered by modulating its tetrathiafulvalene (TTF)-based molecular π-electron system by means of partial sulfur/selenium substitution. The prepared selenium analogue also showed a similar type of phase transition, induced by H-bonded deuterium transfer followed by electron transfer between the H-bonded TTF skeletons, and the resulting switching of the physical properties; however, subtle but critical differences due to sulfur/selenium substitution were detected in the electronic structure, phase transition nature, and switching function. A molecular-level discussion based on the crystal structures shows that this chemical modification of the TTF skeleton influences not only its own π-electronic structure and π-π interactions within the conducting layer, but also the H-bond dynamics between the TTF π skeletons in the neighboring layers, which enables modulation of the interplay between the H-bond and π electrons to cause such differences.