Seleno Analogues Research Articles

A chromatographic relay conjugated photoredox strategy: S, Se-pharmacophore from alkenes via formal [2+2+1] heteroannulation.

An expedient route to 2-aminodihydrothiophenes and their seleno analogues is reported. A three-component photoredox reaction between alkene, thio(seleno)cyanate, and bromomalonate is employed, generating a carbo-thio(seleno)cyanate intermediate that undergoes a domino of reactions mediated by alumina column chromatography, leading to valuable chalcogen pharmacophores. Mechanistic investigations using DFT and control experiments reveals an intramolecular H-bond responsible for driving the domino forward.

Gold(I) Catalysis Applied to the Stereoselective Synthesis of Indeno[2,1-b]thiochromene Derivatives and Seleno Analogues.

A gold(I)-catalyzed cascade reaction for the stereoselective synthesis of sulfur- or selenium-containing indeno[1,2-b]chromene derivatives from o-(alkynyl)styrenes substituted at the triple bond with a thio- or seleno-aryl group is described. The reaction involves a double cyclization process through a proposed key gold-cyclopropyl carbene intermediate that evolves by the intramolecular addition of an aromatic to the cyclopropane ring, affording polycyclic structures. The enantioselective version was studied using gold(I) complexes bearing chiral ligands.

Semisynthesis of Selenoauraptene.

Selenium-containing compounds are gaining more and more interest due to their valuable and promising pharmacological properties, mainly as anticancer and antioxidant agents. Ebselen, the up to now only approved drugs, is well known to possess very good glutathione peroxidase mimicking effects. To date, the most of efforts have been directed to build pure synthetic Se containing molecules, while less attention have been devoted to Se-based semisynthetic products resembling natural compounds like terpenes, polyphenols, and alkaloids. The aim of this short communication is to report the synthesis of the first example of a Se-phenylpropanoids, namely selenoauraptene, containing a selenogeranyl side chain in position 7 of the umbelliferone core. The key step was the Newman-Kwart rearrangement to obtain a selenocarbamate in which the Se atom was directly attached to umbelliferone (replacing its 7-OH function) followed by hydrolysis to get diumbelliferyl diselenide, which was finally easily converted to the desired Se-geranyl derivative in quite a good overall yield (28.5%). The synthesized adduct displayed a greater antioxidant and a radical scavenger in vitro activity than parent auraptene. The procedure we describe herein, to the best of our knowledge for the first time in the literature, represents an easy-to-handle method for the synthesis of a wide array of seleno analogues of naturally occurring biologically active oxyprenylated secondary metabolites.

ATP synthesis in the energy metabolism pathway: a new perspective for manipulating CdSe quantum dots biosynthesized in Saccharomyces cerevisiae.

Due to a growing trend in their biomedical application, biosynthesized nanomaterials are of great interest to researchers nowadays with their biocompatible, low-energy consumption, economic, and tunable characteristics. It is important to understand the mechanism of biosynthesis in order to achieve more efficient applications. Since there are only rare studies on the influences of cellular energy levels on biosynthesis, the influence of energy is often overlooked. Through determination of the intracellular ATP concentrations during the biosynthesis process, significant changes were observed. In addition, ATP synthesis deficiency caused great decreases in quantum dots (QDs) biosynthesis in the Δatp1, Δatp2, Δatp14, and Δatp17 strains. With inductively coupled plasma-atomic emission spectrometry and atomic absorption spectroscopy analyses, it was found that ATP affected the accumulation of the seleno-precursor and helped with the uptake of Cd and the formation of QDs. We successfully enhanced the fluorescence intensity 1.5 or 2 times through genetic modification to increase ATP or SeAM (the seleno analog of S-adenosylmethionine, the product that would accumulate when ATP is accrued). This work explains the mechanism for the correlation of the cellular energy level and QDs biosynthesis in living cells, demonstrates control of the biosynthesis using this mechanism, and thus provides a new manipulation strategy for the biosynthesis of other nanomaterials to widen their applications.

N6-Substituted 5'-N-Methylcarbamoyl-4'-selenoadenosines as Potent and Selective A3 Adenosine Receptor Agonists with Unusual Sugar Puckering and Nucleobase Orientation.

Potent and selective A3 adenosine receptor (AR) agonists were identified by the replacement of 4'-oxo- or 4'-thionucleosides with bioisosteric selenium. Unlike previous agonists, 4'-seleno analogues preferred a glycosidic syn conformation and South sugar puckering, as shown in the X-ray crystal structure of 5'-N-methylcarbamoyl derivative 3p. Among the compounds tested, N6-3-iodobenzyl analogue 3d was found to be the most potent A3AR full agonist (Ki = 0.57 nM), which was ≥800- and 1900-fold selective for A1AR and A2AAR, respectively. In the N6-cycloalkyl series, 2-Cl analogues generally exhibited better hA3AR affinity than 2-H analogues, whereas 2-H > 2-Cl in the N6-3-halobenzyl series. N7 isomers 3t and 3u were much weaker in binding than corresponding N9 isomers, but compound 3t lacked A3AR activation, appearing to be a weak antagonist. 2-Cl-N6-3-iodobenzyl analogue 3p inhibited chemoattractant-induced migration of microglia/monocytes without inducing cell death at ≤50 μM. This suggests the potential for the development of 4'-selenonucleoside A3AR agonists as novel antistroke agents.

A comprehensive theoretical study of mutual interactions between the intramolecular hydrogen bond and π-electron delocalization of RAHB units with the benzene rings in salicylaldehyde and ortho-aminobenzaldehyde with their thio and seleno analogues

A comprehensive theoretical study of mutual interactions between the resonance-assisted hydrogen bond (RAHB) units and benzene rings in salicylaldehyde and ortho-aminobenzaldehyde with their thio and seleno analogues, at the M062X/6-11++G(d,p) level of theory, was carried out. First, we evaluated the intramolecular hydrogen bond (IMHB) strength of the mentioned compounds by various descriptors, such as geometrical, spectroscopic, topological, molecular orbital, and energetic parameters, and then compared with the corresponding results of malonaldehyde and β-aminoacrolein with their thio and seleno analogues. According to the theoretical results, it was found that the merging of benzene rings and RAHB units reduced the strength of the IMHB in all of the benchmark systems. The magnitude of these reductions in the O-H⋯Y systems is greater than that of the N-H⋯Y ones. Also, the substitution of S and Se atoms instead of O increased the IMHB strength and obeyed the following order; X-H⋯Se > X-H⋯S > X-H⋯O. Second, a set of aromaticity indices such as the harmonic oscillator model of aromaticity (HOMA), the nucleus-independent chemical shift (NICS), the para delocalization index (PDI), and the average two-center index (ATI) were applied to evaluate the significance of the aromaticity of benzene rings and π-ED of RAHB units in the studied molecules. The comparison between these results and the respective amounts of the benzene ring, malonaldehyde, and β-aminoacrolein analogues reveals that the coupling of benzene and RAHB rings decreased the π-ED and aromaticity in both of them. These reductions approximately increase with the replacement of O by N in the proton donor group. Finally, the results show that the π-ED of RAHB units increases with substitution of O by S and Se, while for the aromaticity of the benzene rings the reverse process is observed. The majority increment in the π-ED of RAHB units and also a reduction in the aromaticity of the benzene rings are related to an X-H⋯Se system that is followed by X-H⋯S and X-H⋯O systems.

A comparative study of cooperative effects between the intramolecular hydrogen bond and cation···π interaction in various complexes of ortho-aminobenzaldehyde with its thio and seleno analogous

In the present study, a comparative study of cooperative effect between the intramolecular hydrogen bond (IMHB) and cation···π interactions for the first time in some complexes of ortho-aminobenzaldehyde with its thio and seleno analogues at the M062X/6-311++G(d, p) level of theory has been carried out. The energetic, geometric, spectroscopic, topologic and molecular orbital descriptors were used to evaluate the strength of the IMHB and cation···π interactions in the benchmark systems. Based on the energetic results, for the double-charge cations, the coexistence of these non-covalent interactions increases the strength of the cation···π, while for the mono-charge cations the reverse process is observed. However, for both type of the cations (mono- and double charges), this coupling leads to a stronger IMHB. In contrast to the energetic conclusions, the results of the other descriptors indicated that the coupling simultaneously strengthens both of the interactions . On the other hand, the harmonic oscillator model of aromaticity was applied to evaluate the significance of π-electron delocalization (π-ED) within the RAHB unit and aromaticity of benzene ring in the title complexes. These results revealed that the mentioned coupling decreased the π-ED and aromaticity. Furthermore, the change in strengths of the IMHB and cation···π interactions and also the significant of π-ED and aromaticity can be arranged in π···Mg2+ > π···Ca2+ > π···Li+> π···K+ > π···Na+ order. Finally, the sulfur and selenium atoms replaced instead of oxygen to explore their influences on the nature of IMHB, cation···π, π-ED and aromaticity.

Theoretical Study of Terminal Vanadium(V) Chalcogenido Complexes Bearing Chlorido and Methoxido Ligands

Solvent (methanol) coordinated vanadium(V) chalcogenido complexes bearing chlorido and methoxido ligands have been studied computationally by means of density functional (DFT) methods. The gas phase complexes were fully optimized using B3LYP/GEN functionals with 6-31+G⁎⁎ and LANL2DZ basis sets. The optimized complexes show distorted octahedral geometries around the central vanadium atom. The ligand pπ-vanadium dπ interactions were analyzed by natural bond order (NBO) and natural population analyses (NPA). These results show strong stabilization of the V=O bond as was further confirmed by the analyses of the frontier molecular orbitals (FMOs). Second-order perturbation analyses also revealed substantial delocalization of lone pair electrons from the oxido ligand into vacant non-Lewis (Rydberg) orbitals as compared to the sulfido and seleno analogues. These results show significant ligand-to-metal charge transfer (LMCT) interactions. Full interaction map (FIM) of the reference complex confirms hydrogen bond interactions involving the methanol (O-H) and the chlorido ligand.

First Occurrence of a Furano-glycyrrhetinoate and Its Cytotoxicity.

(18α)-Glycyrrhetinic acid (4) was prepared from (18β)-glycyrrhetinic acid (1), and the cytotoxicity of some derivatives was investigated by photometric SRB assays employing several human tumor cell lines. In summary, (18β)-1 is slightly more cytotoxic than its (18α) epimer 4, but its cytotoxicity is negligible. Higher cytotoxicity was observed for the esters 2 and 5 and for the 3-O-acetylated esters 3 and 6. Cytotoxicity was improved dramatically when the hydroxyl group at position C-3 was replaced by an amino moiety. SeO2 oxidations gave access to a novel furano-glycyrrhetinoate 15. Interestingly, its seleno analog 16 is approximately five to six times less cytotoxic for the tumor cell lines tested, and tumor/non-tumor selectivity is lost upon replacement of the oxygen by a selenium substituent.

Coordination polymers of benzenediseleninate, the seleno analog of terephthalate

The proligand para-benzenediseleninic acid, (HO2SeC6H4SeO2H) (Figure), is the seleno analog to the commonly used MOF spacer proligand, terephthalic acid. Novel coordination polymers based on this proligand, and Mn(II), Fe(II), Co(II), Ni(II), Cu(II) or Zn(II) metal centers containing auxiliary water molecules, [M(O2SeC6H4SeO2)2(H2O)n], were synthesized. Depending on the reaction conditions, different pure or mixed phases can be produced. Crystal to crystal transformations of the novel coordination polymers were studied with powder X ray diffraction, infrared spectral analysis and thermal gravimetric analysis. These coordination polymers can be dehydrated with subsequent formation of new anhydrous coordination polymer phases. Some of these phases can be rehydrated to lead back to the crystalline starting materials or to new crystalline hydrated phases. We are working on the complete structural characterization of the phases.

ChemInform Abstract: Heck‐Type Coupling of Intramolecularly‐Generated Thiopalladacycles with Alkenes: One Pot Syntheses of 3‐Alkenylbenzo[b]thiophenes.

AbstractA new methodology for the synthesis of the title compounds and the seleno analogues (IX) is developed.

ChemInform Abstract: A New Strategy for the Stereoselective Synthesis of Olefins.

Abstract Highly stereoselective conversion of ketones into (Z)-olefins, via intermediate S-(β-oxoalkyl)thiophosphates and their seleno analogues is described. Conversion of ketones into corresponding olefins via intermediate thiophosphates and their seleno analogues is reported.

Synthesis and Pesticidal Properties of Thio and Seleno Analogs of Some Common Urea Herbicides

Thio and seleno analogs of fenuron, isoproturon, chlorotoluron, metoxuron, monuron, and diuron were synthesized from the corresponding aryl amines. Their reaction with thiophosgene leads to isothiocyanates. Aryl amines were also converted (via isocyanides) to isoselenocyanates. The reaction of both isothio- and isoselenocyanates with dimethylamine affords the corresponding thio and seleno analogs of the above-mentioned urea herbicides. Herbicidal activity of the synthesized compounds was slightly lower than the activity of the parent urea herbicides. The thio and seleno analogs as well as the parent ureas showed good fungicidal activity at a concentration of 200 ppm against selected fungi.

ChemInform Abstract: Synthesis of Diethyl Cyclopropylphosphonate and Its Thio and Seleno Analogues.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Studies of the Synthesis of Diethyl Cyclopropylphosphonate and Its Thio and Seleno Analogs

Two methods for the synthesis of unsubstituted diethyl cyclopropylphosphonate are described. One method is a reaction between cyclopropylmagnesium bromide and diethyl chlorophosphite to give diethyl cyclopropylphosphonite, followed by oxidation with sodium periodate to the corresponding phosphonate. Alternatively, diethyl cyclopropylphosphonite was reacted with elemental sulfur or selenium to give the thio and seleno analogs, respectively. The second method involves exclusive 1,3‐elimination of HBr from diethyl 3‐bromopropylphosphonate. This method can be directed to either the 1,2‐ or the 1,3‐elimination reaction, leading to propenylphosphonate or cyclopropylphosphonate, depending on the solvent used.

Reaction of thio and seleno phosphoric acid derivatives with O‐thioacylated hydroxylamine

AbstractThe reactivity of thio and seleno analogs of phosphoric acid 1b–f with O‐thioacylhydroxylamine 2 was examined. The experimental evidence for the proposed mechanism involving an N—O bond cleavage and a single electron transfer process (SET) from phosphate anions was collected. The influence of phosphoric acids 1 structure and their oxidation potentials on the course of the reaction and products 3, 4, 6, 7 distribution was presented. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:767–773, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20368

Quantum-chemical study of the structure and reactivity of pyrazol-5-ones and their thio and seleno analogs: X. 1-methylpyrazol-5-one and its thio and seleno analogs in H-complex formation reactions in the gas phase and in solutions

The effects of specific solvation and self-association of chalcogenpyrazol-5-ones are assessed using nonempirical quantum-chemical, density functional theory (DFT), and MP2 second-order perturbation theory methods. The formation of H-complexes with water, methanol, and DMSO stabilizes all tautomeric forms, the NH tautomers of all hetero analogs being the most affected. The NH tautomers form with water 1:2 complexes which reveal cooperativity. The complexes of chalcogenpyrazolones with DMSO are more stable than the respective complexes with water, and, therewith, the extra stabilization in continuum is less pronounced than in the case of hydration. Quantitatively, the effects of tautomer self-association compare with the effects of interaction of chalcogenpyrazolones with proton-donor solvents.

Quantum-chemical study of the structure and reactivity of 4,5-dihydropyrazol-5-ones and their thio and seleno analogs: VIII. Solvation effects and tautomerism of 4,5-dihydropyrazol-5-ones and their thio and seleno analogs

The effect of hydration on the stability of tautomeric forms of 1-methyl-4,5-dihydro-1H-pyrazol-5-one, 1-methyl-4,5-dihydro-1H-pyrazole-5-thione, and 1-methyl-4,5-dihydro-1H-pyrazole-5-selone was analyzed by nonempirical quantum-chemical methods at different theory levels. The results of calculations by all these methods, including density functional theory, with two types of models (continuum and discrete) showed stronger stabilization of the NH tautomers of all the examined heteropyrazolones in water, as compared to their CH and XH tautomers. The strongest stabilization effect is reached in the calculation of discrete complexes in terms of the self-consistent reaction field model. The degree of differentiation of the stability of tautomeric forms considerably decreases when electronic correlation is taken into account, whereas the use of polarization functions on hydrogen atoms in addition to polarization functions on heavy atoms almost does not affect the position of the tautomeric equilibrium.

Structure–activity studies of uptake and phototoxicity with heavy-chalcogen analogues of tetramethylrosamine in vitro in chemosensitive and multidrug-resistant cells

Several thio and seleno analogues of tetramethylrosamine ( TMR) were prepared. Thio derivatives of TMR have absorption maxima near 570 nm, while seleno derivatives of TMR have absorption maxima near 580 nm. The 3- or 4- N, N-dimethylaminophenyl substituent in the 9-position greatly increases internal conversion, which lowers quantum yields for fluorescence and the generation of singlet oxygen. Thio and seleno analogues of TMR are effective photosensitizers against chemosensitive AUXB1 cells in vitro and against multidrug-resistant CR1R12 cells in vitro, which have been treated with verapamil. The CR1R12 cells accumulated significantly lower concentrations of the photosensitizers relative to the AUXB1 cells presumably due to the expression of P-glycoprotein (Pgp) in the CR1R12 cells. Following treatment with 5 × 10 −5 M verapamil, the uptake in CR1R12 cells of several fluorescent thio analogues of TMR is comparable to that observed for the chemosensitive AUXB1 cells.

IMP dehydrogenase from the protozoan parasite Toxoplasma gondii.

The opportunistic apicomplexan parasite Toxoplasma gondii damages fetuses in utero and threatens immunocompromised individuals. The toxicity associated with standard antitoxoplasmal therapies, which target the folate pathway, underscores the importance of examining alternative pharmacological strategies. Parasitic protozoa cannot synthesize purines de novo; consequently, targeting purine salvage enzymes is a plausible pharmacological strategy. Several enzymes critical to purine metabolism have been studied in T. gondii, but IMP dehydrogenase (IMPDH), which catalyzes the conversion of IMP to XMP, has yet to be characterized. Thus, we have cloned the gene encoding this enzyme in T. gondii. Northern blot analysis shows that two IMPDH transcripts are present in T. gondii tachyzoites. The larger transcript contains an open reading frame of 1,656 nucleotides whose deduced protein sequence consists of 551 amino acids (TgIMPDH). The shorter transcript is an alternative splice product that generates a 371-amino-acid protein lacking the active-site flap (TgIMPDH-S). When TgIMPDH is expressed as a recombinant protein fused to a FLAG tag, the fusion protein localizes to the parasite cytoplasm. Immunoprecipitation with anti-FLAG was employed to purify recombinant TgIMPDH, which converts IMP to XMP as expected. Mycophenolic acid is an uncompetitive inhibitor relative to NAD+, with a intercept inhibition constant (Kii) of 0.03+/-0.004 microM. Tiazofurin and its seleno analog were not inhibitory to the purified enzyme, but adenine dinucleotide analogs such as TAD and the nonhydrolyzable beta-methylene derivatives of TAD or SAD were inhibitory, with Kii values 13- to 60-fold higher than that of mycophenolic acid.