Tellurium-containing Compounds Research Articles

Potentials of organic tellurium-containing compound AS101 to overcome carbapenemase-producing Escherichia coli.

The issue of carbapenem-resistant Escherichia coli was aggravated yearly. The previous studies reported the varied but critical epidemiology of carbapenem-resistant E. coli among which the carbapenemase-producing strains were regarded as one of the most notorious issues. AS101, an organic tellurium-containing compound undergoing clinical trials, was revealed with antibacterial activities. However, little is known about the antibacterial effect of AS101 against carbapenemase-producing E. coli (CPEC). The minimum inhibitory concentration (MIC) of AS101 against the 15 isolates was examined using a broth microdilution method. The scanning electron microscopy, pharmaceutical manipulations, reactive oxygen species level, and DNA fragmentation assay were carried out to investigate the antibacterial mechanism. The sepsis mouse model was employed to assess the invivo treatment effect. The blaNDM (33.3%) was revealed as the dominant carbapenemase gene among the 15 CPEC isolates, followed by the blaKPC gene (26.7%). The MICs of AS101 against the 15 isolates ranged from 0.5 to 32μg/ml, and 99.9% of bacterial eradication was observed at 8h, 4h, and 2h for 1×, 2×, and 4×MIC, respectively. The mechanistic investigations suggest that AS101 would enter the bacterial cell, and induce ROS generation, leading to DNA fragmentation. The invivo study exhibited that AS101 possessed a steady treatment effect in a sepsis mouse model, with an up to 83.3% of survival rate. The invitro activities, mechanisms, and invivo study of AS101 against CPEC were unveiled. Our finding provided further evidence for the antibiotic development of AS101.

SYNTHESIS OF THIAZOLOQUINAZOLINARYLTELLURID

Symmetric and asymmetric chalcogenides of organic nature are a class of organometallic compounds that are widely used as intermediates in a number of organic reactions, as ligands in the chemistry of coordination compounds, they have a wide range of biological activity. Diaryl tellurides, which are important for the formation of new carbon-carbon bonds, have a special area in the chemistry of organotelluric compounds. The synthesis of new representatives of this class of tellurium-containing compounds is an urgent task.
 One of the main methods of obtaining of diaryl tellurides is the interaction of arylboronic acids with diarylditellurides in the presence of various metal-containing catalysts or microwave radiation. In this paper, we have considered the method of obtaining asymmetric tellurides by the reaction of reduction of sodium sulfite with salts of thiazoloquinazolinaryl dichlorotellurides without the usage of catalysts.
 It was found that the reaction of 2-((dichloro(4-methoxyphenyl)-4-tellanyl)methyl)-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one hydrochloride with triple excess of sodium sulfite leads to the formation of 2-((4-methoxyphenyl)tellanyl)methyl)-2,3-dihydro-5H-thiazolo [2,3-b]quinazolin-5-one. It should be noted that the recovery does not break the bond Te-C. In the analysis of spectral data, the signals of the protons of the thiazole cycle and the exocyclic aryltelluric fragment undergo a strong field shift.
 Thus, as a result of the reduction reaction of 2-((dichloro(4-methoxyphenyl)-4-tellanyl)methyl)-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one hydrochloride, a biologically promising and suitable for further functionalization telluride was received.

Selenium and tellurium in the development of novel small molecules and nanoparticles as cancer multidrug resistance reversal agents.

Selenium is an essential trace element that is crucial for cellular antioxidant defense against reactive oxygen species (ROS). Recently, many selenium-containing compounds have exhibited a wide spectrum of biological activities that make them promising scaffolds in Medicinal Chemistry, and, in particular, in the search for novel compounds with anticancer activity. Similarly, certain tellurium-containing compounds have also exhibited substantial biological activities. Here we provide an overview of the biological activities of seleno- and tellurocompounds including chemopreventive activity, antioxidant or pro-oxidant activity, modulation of the inflammatory processes, induction of apoptosis, modulation of autophagy, inhibition of multidrug efflux pumps such as P-gp, inhibition of cancer metastasis, selective targeting of tumors and enhancement of the cytotoxic activity of chemotherapeutic drugs, as well as overcoming tumor drug resistance. A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.

ARYLTELLUROCHLORINATION OF N-ALLYLTHIOAMIDE OF TRIFLUOROACETIC ACID

Telluroganic compounds have a pronounced biological activity, namely, show antitumor, antioxidant, antiparasitic activity. The introduction of a trifluoromethyl group to such compounds can significantly increase the activity. Therefore, the aim of this study is the synthesis of tellurium-containing compounds by the electrophilic action of aryltellurium trichloride on N-allylthioamide of trifluoroacetic acid.
 As the object of the study of the aryltellurohalogenation process of N-allyl thioamide of trifluoroacetic acid was chosen. The selection is dictated by the presence of several nucleophilic centers suitable for the attack by electrophiles and can form both addition and cyclization products. The synthesis of the amide was performed through the interaction of ethyl ester of trifluoroacetic acid with allylamine in tetrahydrofuran followed by the treatment of the formed N-allylamide with phosphorus (V) sulfide in the presence of hexamethyldisiloxane in toluene.
 Propargyl trifluoroacetic acid amide was investigated in the halogenation reaction, which resulted in the addition product. It was important to establish the effect of the nature of the unsaturated alkenyl/alkynyl substituent, the additional nucleophilic center and the electrophilic reagent on the reaction pathway. The reaction of N-allyltrifluorothioacetamide with p-methoxyphenyltellurium trichloride was performed in chloroform or tetrahydrofuran at room temperature in equimolar amounts of reagents. The addition product N-(2-chloro-3- (dichloro (4-methoxyphenyl) -)-l4-4-tellanyl)propyl] -2,2,2-trifluoroethanethioamide was obtained. Similar addition products were formed in the reaction of N-allyl thioureas with aryltellurium trihalides.

Complementary Performance of Organoselenides and Organotellurides as Antimicrobials Agents

Fungi and bacteria are well-known pathogens for plants, fruits, and animals, including humans. In this context, the prospection of antimicrobial agents is crucial to provide new alternatives for the treatment of microbial diseases. Hence, selenium- and tellurium-containing compounds are underexploited and herein, antimicrobial activity of several organochalcogenated compounds was evaluated against Gram-negative and Gram-positive bacteria and fungi. A direct comparison between Se- and Te-containing compounds was performed, as well as structure-activity relationship studies. Among assayed compounds, secondary Se-amines LQ16 and LQ20 and secondary Te-amine LQ28 showed excellent results against a variety of fungi, while primary Te-amine LQ10 demonstrated promising results against bacteria. These results suggest organoselenides and organotellurides may be used for the development of new antimicrobial agents.

Tellurides Bearing Sulfonamides as Novel Inhibitors of Leishmanial Carbonic Anhydrase with Potent Antileishmanial Activity.

We report for the first time a novel series of tellurides bearing sulfonamide as selective and potent inhibitors of the β-class carbonic anhydrase (CA; EC 4.2.1.1) enzyme expressed in Leishmania donovani protozoa. Such derivatives showed high activity against axenic amastigotes, and among them, compound 5g (4-(((3,4,5-trimethoxyphenyl)tellanyl)methyl)benzenesulfonamide) showed an IC50 of 0.02 μM being highly selective for the parasites over THP-1 cells with a selectivity index of 300. The in vitro and in vivo toxicity experiments showed compound 5g to possess a safe profile and thus paving the way for tellurium-containing compounds as novel drug entities.

Nickel - p-block metal mixed chalcogenides based on AuCu3-type fragments: iodine-assisted synthesis as a way of obtaining new structures.

Two new mixed nickel-gallium chalcogenides, Ni9.39Ga2S2 and Ni5.80GaTe2, and a new mixed nickel-indium telluride, Ni5.78InTe2, have been synthesized by a high-temperature ampoule route with the addition of iodine, and characterized from single-crystal or powder diffraction data. They belong to the relatively uncommon Ni7-xMQ2/Ni10-xM2Q2 type of structures (M = Ge, Sn, Sb, In), and are built from p-block metal-centered nickel cuboctahedra, alternating along the c axis with defective Cu2Sb-type nickel-chalcogen ones. Both tellurium-containing compounds show a small degree of orthorhombic distortion with respect to the idealized tetragonal structure, only detectable in the powder diffraction data. No phase transition to the tetragonal structure was detected for Ni5.80GaTe2 by the in situ powder diffraction measurements from room temperature to 550 °C. DFT calculations show close relationships of electronic structures of these ternary compounds to their parent intermetallics, Ni3M (M = Ga, In). Metallic conductivity and paramagnetic properties are predicted for all three with the latter confirmed by magnetic measurements. The bonding patterns, investigated via the ELF topological analysis, show multi-centered nickel - p-block metal bonds in the AuCu3-type fragments and pairwise covalent interactions in the nickel-chalcogen fragments. Both Ni7-xMTe2 compounds showed no structural or compositional changes upon high-temperature mid-pressure hydrogenation.

Multiplicity of Te–Te Bonds in Tellurium-Containing Lanthanide Compounds

The structures of 272 compounds containing 337 LnTen coordination polyhedra, where Ln is any lanthanide from La to Lu in the crystals, are analyzed using Voronoi–Dirichlet(VD) polyhedra. It is shown that the parameters of VD polyhedra allow determination of the valence state of Ln atoms. It is established that tellurides contain Ln(II) and Ln(III) atoms bonding from 4 to 9 tellurium atoms that exist as Te2–or Tе− ions. The VD polyhedra of Te atoms are determined and it is found that homoatomic Te–Te bonds appear only when there is a deficit of electron donor metal atoms in the composition of crystalline compounds. The dependence of the multiplicity of the Te–Te covalent bond on its length is revealed through the parameters of VD polyhedra. The reliability of this dependence is tested for some compounds, including polytellurides containing 44 networks of tellurium atoms.

Insights into the differential toxicological and antioxidant effects of 4-phenylchalcogenil-7-chloroquinolines in Caenorhabditis elegans

Organic selenium and tellurium compounds are known for their broad-spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high-throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C. elegans) as a model for the assessment of pharmacological and toxicological parameters following exposure to two 4-phenylchalcogenil-7-chloroquinolines derivatives (PSQ for selenium and PTQ for tellurium-containing compounds). While non-lethal concentrations (NLC) of PTQ and PSQ attenuated paraquat-induced effects on survival, lifespan and oxidative stress parameters, lethal concentrations (LC) of PTQ and PSQ alone are able to impair these parameters in C. elegans. We also demonstrate that DAF-16/FOXO and SKN-1/Nrf2 transcription factors underlie the mechanism of action of these compounds, as their targets sod-3, gst-4 and gcs-1 were modulated following exposures in a daf-16- and skn-1-dependent manner. Finally, in accordance with a disturbed thiol metabolism in both LC and NLC, we found higher sensitivity of trxr-1 worm mutants (lacking the selenoprotein thioredoxin reductase 1) when exposed to PSQ. Finally, our study suggests new targets for the investigation of organochalcogen pharmacological effects, reinforcing the use of C. elegans as a powerful platform for preclinical approaches.

First example of the correlated calculation of the one-bond tellurium-carbon spin-spin coupling constants: Relativistic effects, vibrational corrections, and solvent effects.

This work reports on the comprehensive calculation of the NMR one-bond spin-spin coupling constants (SSCCs) involving carbon and tellurium, (1) J((125) Te,(13) C), in four representative compounds: Te(CH3 )2 , Te(CF3 )2 , Te(CCH)2 , and tellurophene. A high-level computational treatment of (1) J((125) Te,(13) C) included calculations at the SOPPA level taking into account relativistic effects evaluated at the 4-component RPA and DFT levels of theory, vibrational corrections, and solvent effects. The consistency of different computational approaches including the level of theory of the geometry optimization of tellurium-containing compounds, basis sets, and methods used for obtainig spin-spin coupling values have also been discussed in view of reproducing the experimental values of the tellurium-carbon SSCCs. Relativistic corrections were found to play a major role in the calculation of (1) J((125) Te,(13) C) reaching as much as almost 50% of the total value of (1) J((125) Te,(13) C) while relativistic geometrical effects are of minor importance. The vibrational and solvent corrections account for accordingly about 3-6% and 0-4% of the total value. It is shown that taking into account relativistic corrections, vibrational corrections and solvent effects at the DFT level essentially improves the agreement of the non-relativistic theoretical SOPPA results with experiment. © 2016 Wiley Periodicals, Inc.

(77)Se and (125)Te NMR spectroscopy on a selectivity study of organochalcogenanes with L-amino acids.

The hypervalent selenium- and tellurium-containing compounds (halo-organoselenuranes and halo-organotelluranes) were treated with amino acids to evaluate their reactivity and chemoselectivity by (1)H, (13)C, (77)Se and (125)Te NMR spectroscopy. The study of forced thermal stability was performed and analyzed by NMR. The organotelluranes remained stable at temperatures around 60 °C but in the case of organoselenuranes, there was formation of new products at 37 °C as a result of halogen loss. (77)Se and (125)Te NMR spectroscopy has proved to be a very efficient and fast technique to evidence the high selectivity of organochalcogenanes against l-amino acids, specific to l-cysteine.

Bacterial recovery and recycling of tellurium from tellurium-containing compounds by Pseudoalteromonas sp. EPR3.

Tellurium-based devices, such as photovoltaic (PV) modules and thermoelectric generators, are expected to play an increasing role in renewable energy technologies. Tellurium, however, is one of the scarcest elements in the earth's crust, and current production and recycling methods are inefficient and use toxic chemicals. This study demonstrates an alternative, bacterially mediated tellurium recovery process. We show that the hydrothermal vent microbe Pseudoalteromonas sp. strain EPR3 can convert tellurium from a wide variety of compounds, industrial sources and devices into metallic tellurium and a gaseous tellurium species. These compounds include metallic tellurium (Te(0)), tellurite (TeO3(2-)), copper autoclave slime, tellurium dioxide (TeO2), tellurium-based PV material (cadmium telluride, CdTe) and tellurium-based thermoelectric material (bismuth telluride, Bi2Te3). Experimentally, this was achieved by incubating these tellurium sources with the EPR3 in both solid and liquid media. Despite the fact that many of these tellurium compounds are considered insoluble in aqueous solution, they can nonetheless be transformed by EPR3, suggesting the existence of a steady state soluble tellurium concentration during tellurium transformation. These experiments provide insights into the processes of tellurium precipitation and volatilization by bacteria, and their implications on tellurium production and recycling.

A new tellurium-containing amphiphilic molecule induces apoptosis in HCT116 colon cancer cells

BackgroundChalcogen-based redox modulators over the years have attracted considerable attention as anti-cancer agents. New selenium- and tellurium-containing compounds with a polar head group and aryl-groups of various lengths have recently been reported as biologically active in several organisms. In the present study, we used the most active of the tellurium compound DP41, and its selenium counterpart DP31 to investigate their effects on the human cancer cell line HCT116. MethodsCells were treated with DP41 or DP31 and the formation of superoxide radicals was determined using dihydroethidium. Cell cycle analysis and apoptosis was determined by cytofluorimetry. Proteins involved in ER signaling and apoptosis were determined by Western blot analysis and fluorescence microscopy. ResultsWith 50μM of DP41, we observed an increase in O2− formation. There was, however, no such increase in O2− after treatment with the corresponding selenium compound under the same conditions. In the case of DP41, the production of O2− radicals was followed by an up-regulation of Nrf2, HO-1, phospho-eIF2α and ATF4. CHOP was also induced and cells entered apoptosis. Unlike the cancer cells, normal retinal epithelial ARPE-19 cells did not produce elevated levels of O2− radicals nor did they induce the ER signaling pathway or apoptosis. ConclusionsThe tellurium-containing compound DP41, in contrast to the corresponding selenium compound, induces O2− radical formation and oxidative and ER stress responses, including CHOP activation and finally apoptosis. General significanceThese results indicate that DP41 is a redox modulating agent with promising anti-cancer potentials.

20S proteasome as novel biological target for organochalcogenanes

A series of hypervalent selenium- and tellurium-containing compounds (organoselenuranes and organotelluranes) was evaluated aiming novel inhibitors of a threonine protease, namely the 20S proteasome (20S PT). In vitro assays demonstrated high inhibitory potency and specificity of these compounds toward the β2 catalytic site of the 20S PT. Organotelluranes were identified as more potent inhibitors than organoselenuranes since their IC50 ranged from 3.5 to 16 μM while for organoselenuranes the IC50 ranged from 16 to 35 μM indicating great potential to be explored in 20S proteasome inhibition. Cellular assays with those compounds were employed to verify the cytotoxicity and ability to inhibit 20S proteasome in cell. These assays demonstrated that organoselenuranes are capable of maintaining their selectivity in cell while the organotelluranes became inactive under cellular conditions. Stability studies of the organochalcogenanes were performed by 77Se and 125Te NMR analysis. It was observed that organotelluranes are stable under enzymatic assay conditions and, organoselenuranes, the structures responsible for inhibitory activity are cyclized organoselenuranes.

Construction of the Active Site of Glutathione Peroxidase on Polymer-Based Nanoparticles

A new nanoenzyme model with glutathione peroxidase-like active site was constructed on polystyrene nanoparticle (PN1) via microemulsion polymerization. In this model system, two functional monomers were designed: one is a tellurium-containing compound that was introduced on the surface of the nanoparticle and acts as a catalytic center, and the other one is an arginine-containing compound designed as a binding site for the complexation of the carboxyl group of substrate 3-carboxy-4-nitrobenzenethiol (ArSH, 1). As a new glutathione peroxidase (GPx) mimic, it demonstrated excellent catalytic activity and substrate specificity. In ArSH assay system, it was at least 316,000-fold more efficient than PhSeSePh for the reduction of cumene hydroperoxide (CUOOH) by ArSH. In contrast to model PN2, which lacks of substrate binding site, PN1 exhibits an obvious enhancement in catalytic activity. To further promote the catalytic efficiency, a substrate ArSH surface-imprinted nanoenzyme model (I-PN) was developed. By correctly incorporating and positioning the catalytic center tellurium and functional binding factor guanidinium, a continuative activity enhancement of 596,000-fold for the reduction of CUOOH by catalyst I-PN compared with diphenyl diselenide (PhSeSePh) was observed. The results clearly show that polymeric nanoparticle can be developed as an excellent model for combining most of catalytic factors of enzyme into one scaffold.

Cytometric determination of novel organotellurium compound toxicity in a promyelocytic (HL-60) cell line.

The increasing use of tellurium compounds in organic synthesis, industrial applications, and as a possible component in pesticides means that its introduction into the environment will increase in the future. Therefore, knowledge of the relative toxicity and mode of toxic action of tellurium-containing compounds is important. The studies detailed here used three model compounds: diphenyl ditelluride, 3,3'-diaminodiphenyl ditelluride, and 4,4'-diisopropyldiphenyl ditelluride. Experiments with human promyelocytic (line HL-60) cells indicate that all of the organotellurium compounds induce an apoptotic form of cell death. The induction of apoptosis occurs in a time- and dose-dependent manner as assayed by three different analytical methods: fluorescence microscopy, gel electrophoresis, and flow cytometry. Apoptotic cells were evident as early as 2 h following treatment with 1x10(-6) M concentrations of the compounds. Based on these results, future care should be afforded these compounds in laboratory as well as industrial settings.

Interaction of peroxynitrite with selenoproteins and glutathione peroxidase mimics

Peroxynitrite is an oxidant generated under inflammatory conditions, acting in defense against invading microorganisms. There is a need for protection of the organism from damage inflicted by peroxynitrite. Selenium-containing compounds, notably ebselen, have a high second-order reaction rate constant (approx. 2 × 10 6 M −1 s −1), which makes them candidates for efficient protection. This applies also for selenium in proteins, occurring as selenocysteine or selenomethionine residues. Glutathione peroxidases, thioredoxin reductase, and selenoprotein P have been shown to play a potential role in protection against peroxynitrite. Tellurium-containing compounds also react with peroxynitrite.

Computational Investigations of the Chalcogen-Substituted Carboxylic Acids RC(=O)XH and RC(=X)OH and their Dimers [RC(=O)XH] 2 and [RC(=X)OH] 2 (X=S, Se, Te)

Semiempirical and ab initio theoretical methods have been used to investigate molecular structures of the chalcogen-substituted carboxylic acid isomers RC(=O)XH (chalcogenol acid) and RC(=X)OH (chalcogenon acid). A recent experimental report suggests that the chalcogenon isomers, although less stable at room temperature, predominate at low temperature in polar solvents and that there is only a small barrier to isomerization between the isomers. Theoretical calculations have been used to locate minimum energy structures of chalcogen-substituted carboxylic acid isomers and to calculate energy differences between pairs of isomers. Carboxylic acids are well known to dimerize, especially in the gas phase and in non-polar solvents. We have, therefore, also calculated energies of dimerization of the chalcogen-substituted acids by optimizing the geometries of the symmetric dimers. We note that the PM3 level of theory is only qualitatively correct for sulfur- and selenium-containing species but fails even qualitatively for the tellurium-containing compounds. Ab initio results confirm the experimental observations and provide good estimates of both isomerization and dimerization energies. We conclude that for many functional groups with tautomers RC(=X)YH and RC(=Y)XH, the more acidic tautomer is the one with the acid proton on the smaller, more electronegative atom, although in many cases this may not be the more stable tautomer.

Determination of Tellurium in Urine by Isotope Dilution Gas Chromatography/Mass Spectrometry Using (4-Fluorophenyl)Magnesium Bromide as a Derivatizing Agent and a Comparison with Electrothermal Atomic Absorption Spectrometry

The antitumor drug AS-101 [ammoniumtrichloro (dioxoethylene-O,O')tellurate(IV)] is the first tellurium-containing compound that has been identified as possessing immunomodulating properties and minimal toxicity. We have developed a stable isotope dilution gas chromatography/mass spectrometry method using 120Te as an internal standard and (4-fluorophenyl)magnesium bromide as a derivatizing agent for Te determination in urine. The urine samples were digested using HNO3 + H2O2 prior to derivatization with lithium bis(trifluoroethyl)dithiocarbamate at a pH of 3. The trifluorodiethyldithiocarbamate of tellurium was reacted with the Grignard reagent in anhydrous diethyl ether to obtain Te-(FC6H4)2 for GC/MS analysis. All isotope ratio measurements were made by selected ion monitoring with a Finnigan MAT 8230 organic mass spectrometer using a 10-m fused silica capillary column. Overall percision values for the five major Te isotopes relative to 130Te were 0.6-3.1% when 10-ng samples of chelated Te were analyzed. No appreciable memory or carry-over effect was observed when two synthetic mixtures differing in 120Te:130Te ratios by a factor of 50 were sequentially analyzed. The isotope dilution GC/MS method was validated by determining Te in urine samples and comparing the values with electrothermal atomic absorption spectrometry. Te concentrations were determined in the 100-500 micrograms/L range with CVs of 1-4%.

Thermal and structural study of the phase transformations of the tellurites of trivalent iron and chromium

The thorough and complete extraction of the basic metals, as well as of the metalloids such as selenium and tellurium, is unthinkable without knowledge of the thermal and structural properties of their respective compounds. Selenium and tellurium are finding ever increasing applications. It is known that they are contained most often in the sulphide minerals, and in the main they are associated with the heavy non-ferrous metals. Selenium and tellurium are concentrated in the intermediate slimes from the electrolysis of copper and nickel or in the wastes from lead-zinc production. Contemporary methods for processing the intermediate slimes involve an oxidative or oxidative-sublimative roasting process with subsequent hydrochemical extraction of the valuable components. Literature reports on the behaviour of the selenides and tellurides (basic selenium- and tellurium-containing compounds in the intermediate slimes) in the roasting process and on the thermal stability of selenites are incomplete, and those on tellurites and tellurates are almost non-existent. For that reason investigation of the thermal behaviour of selenium- and tellurium-containing materials appears to be a pressing problem. This work is devoted to clarifying one of the questions in this many-sided problem-investigation and calculation of the melting temperatures as well as the enthalpies and entropies of such substances. PHASE STATE OF THE TELLURITES