Heteroatom-directed aromatic lithiation: a versatile route to the synthesis of organochalcogen (Se, Te) compounds

Chiral and achiral organochalcogen compounds bearing a heteroatom in close proximity are easily accessible via the directed aromatic lithiation route. The lithium chalcogenolates prepared by the insertion of selenium or tellurium into the C-Li bond are used to synthesize various chalcogen compounds such as Se/Te, N donor ligands, dichalcogenides, monomeric metal chalcogenolates, and macrocycles. The differences in the stability and reactivity of the organochalcogen compounds derived from various substrates are described in terms of electronic and stereochemical properties of donor atoms.     

On Dimensionality of Halogen-Bonded Thiophene Solid-State Assemblies

We report on the structures of three dibromothiophene compounds ( 4 , 5 , and 12 ) and the analysis of the patterns of self-assembly in the solid state by C Br⋅⋅⋅Br C halogen bonds of a selected set of 16 di- or poly-bromine (poly)thiophene monomers sorted according to the dimensionality of their halogen-bonded, extended frameworks thereby identifying syn- or anti-strings and layers. We conclude that in 1 , 2 , 9 , and 10 , the antiparallel orientation of successive C Br⋅⋅⋅Br C halogen-bonded dibromothiophene units along extended anti-strings is linked to the occurrence of solid-state polymerization.     

Se⋅⋅⋅O/S and S⋅⋅⋅O Chalcogen Bonds in Small Molecules and Proteins: A Combined CSD and PDB Study

The importance of selenium-centered noncovalent chalcogen bonds represented as Se⋅⋅⋅A (A=O/S) has been explored for short directional contacts in small molecules and proteins. In addition, S⋅⋅⋅O centered contacts have been analyzed. Computational analyses involving the quantitative assessment of the associated energetics, the molecular electrostatic potentials (MEP), and electron density derived topological parameters, namely, quantum theory of atom in molecules (QTAIM) analyses, and NBO (natural bond orbital) based calculations, have been performed to unequivocally establish the strength, stability, and attractive role of chalcogen bonds in the solid-state. This investigation has been performed in molecules from both the Cambridge Structural Database (CSD) and Protein Data Bank (PDB). Thus futuristic materials may be designed keeping in mind the significance of these interactions, including their relevance in biology.     

S-Denitrosylase-Like Activity of Cyclic Diselenides Conjugated with Xaa-His Dipeptide: Role of Proline Spacer as a Key Activity Booster

This study developed dipeptide-conjugated 1,2-diselenan-4-amine ( 1 ), i. e., 1 -Xaa-His, as a new class of S-denitrosylase mimic. The synthesized compounds, especially 1 -Pro-His, remarkably promoted S-denitrosylation of nitrosothiols (RSNO) via a catalytic cycle involving the reversible redox reaction between the diselenide and its corresponding diselenol ([SeH,SeH]) form with coexisting reductant thiols (R′SH), during which the [SeH,SeH] form as a key reactive species reduces RSNO to the corresponding thiol (RSH). Structural analyses of 1 -Pro-His suggested that the peptide backbone of [SeH,SeH] is rigidly bent to form a γ-turn, possibly including an NH⋅⋅⋅Se hydrogen bond between the imidazole ring of His and selenol group, thus stabilizing the [SeH,SeH] form thermodynamically, and dramatically enhancing the catalytic activity. Furthermore, the synthetic compounds were found to prohibit S-nitrosylation-induced protein misfolding in the presence of RSNO, eventually implying their potential as a drug seed for misfolding diseases caused by the dysregulation of the S-denitrosylation system.     

Additive-Free Enzymatic Phosphorylation and Ligation of Artificial Oligonucleotides with C-Nucleosides at the Reaction Points

We report enzymatic phosphorylation and additive-free ligation of DNAs containing unnatural C-nucleotide residues through the action of T4 polynucleotide kinase and T4 DNA ligase. The artificial units are each made up of an alkynyl deoxyribose component and one of the unnatural nucleobases D * , T * , G * , and C * , corresponding—from a viewpoint of hydrogen-bonding patterns—to natural A, T, G, and C, respectively. Phosphorylation progressed quantitatively at the 5′-end in the cases of all of the artificial units in the chimeric DNAs. Ligation also smoothly progressed at the 5′-end in the cases of the D* and G* nucleotide residues, but only negligibly in those of their T* and C* counterparts. Chemical redesign of the last two units successfully improved the ligation efficiency, so that enzymatic ligation worked well for all of the artificial units in every 3′-natural ⋅ 5′-artificial, 3′-artificial ⋅ 5′-natural, and 3′-artificial ⋅ 5′-artificial terminal combination at the nicks.     

Investigations on Structural and Electrochemical Properties of Some Disulfides Prepared by Schiff Base Reactions

Four different disulfides, [2,2′‐dithiobis‐(2‐mercaptoacetophenone)]‐4‐triphenylmethylthiosemicarbazone ( 1 ), [5,5′‐dithiobis‐(4‐formyl‐3‐methyl‐1‐phenylpyrazole)]‐4‐triphenylmethylthiosemicarbazone ( 2 ), bis[1‐(2‐mercaptophenyl)‐2‐(4‐(1‐phenyl‐3‐methyl)pyrazole)‐azaethene]di‐sulfide ( 3 ) and bis[1‐phenyl‐2‐(4‐(1‐phenyl‐3‐methyl‐5‐mercapto) pyrazole)‐azaethene]disulfide ( 4 ) were synthesized by Schiff base reactions. Their electrochemical behaviour was examined by cyclic voltammetry. The results show low potentials for the disulfide reduction so that these compounds are suitable for the syntheses of tridentate thiolate ligands from disulfides by electrochemical cleavage. In addition compounds 2 and 4 were characterized by X‐ray structure determination. The structures show significant differences of the S—S bonds and angles as compared to other disulfides without bulky substituents.     

Insights into the Mechanism of Human Deiodinase 1

The three isoenzymes of iodothyronine deiodinases (DIO1-3) are membrane-anchored homo-dimeric selenoproteins which share the thioredoxin-fold structure. Several questions regarding their catalytic mechanisms still remain open. Here, we addressed the roles of several cysteines which are conserved among deiodinase isoenzymes and asked whether they may contribute to dimerization and reduction of the oxidized enzyme with physiological reductants. We also asked whether amino acids previously identified in DIO3 play the same role in DIO1. Human DIO1 and 2 were recombinantly expressed in insect cells with selenocysteine replaced with cysteine (DIO1^U126C) or in COS7 cells as selenoprotein. Enzyme activities were studied by radioactive deiodination assays with physiological reducing agents and recombinant proteins were characterized by mass spectrometry. Mutation of Cys124 in DIO1 prevented reduction by glutathione, while 20 mM dithiothreitol still regenerated the enzyme. Protein thiol reductants, thioredoxin and glutaredoxin, did not reduce DIO1^U126C. Mass spectrometry demonstrated the formation of an intracellular disulfide between the side-chains of Cys124 and Cys(Sec)126. We conclude that the proximal Cys124 forms a selenenyl-sulfide with the catalytic Sec126 during catalysis, which is the substrate of the physiological reductant glutathione. Mutagenesis studies support the idea of a proton-relay pathway from solvent to substrate that is shared between DIO1 and DIO3.     

噻吩和苯并噻吩在原位氢存在下的还原脱硫

研究了噻吩和苯并噻吩在原位氢和硼化镍存在下的还原脱硫。实验对操作条件进行了优化;研究了可能的反应机理。结果表明,六水合氯化镍与还原剂于质子溶剂中反应的对硫化物脱硫,产生的原位氢脱硫活性较高;还原剂用量为0.64 g时,脱硫率可达99%以上。噻吩和苯并噻吩脱硫主要发生直接氢解反应;少量苯并噻吩脱硫经由加氢途径进行,硫化物主要通过S原子"端连吸附"在硼化镍表面。推测反应机理为,反应中大量原位氢吸附在硼化镍表面并活化;硼化镍中富电子镍介入硫化物分子中C—S键形成加合物,与活性原位氢进一步作用,使C—S和C—C键断裂。     

Regioselective ring-opening of aziridines with diselenides and disulfides using the Zn/AlCl3 system

An efficient Zn/AlCl₃-promoted highly regioselective one-pot procedure has been demonstrated for the synthesis of β -amino selenides and sulfides from a variety of diselenides/disulfides and aziridines by reductive cleavage of Se–Se and S–S bonds using the Zn/AlCl₃ system in acetonitrile under very mild conditions.

     

In Vitro Metabolism of Six C-Glycosidic Flavonoids from Passiflora incarnata L.

Several medical plants, such as Passiflora incarnata L., contain C-glycosylated flavonoids, which may contribute to their efficacy. Information regarding the bioavailability and metabolism of these compounds is essential, but not sufficiently available. Therefore, the metabolism of the C-glycosylated flavones orientin, isoorientin, schaftoside, isoschaftoside, vitexin, and isovitexin was investigated using the Caco-2 cell line as an in vitro intestinal and epithelial metabolism model. Isovitexin, orientin, and isoorientin showed broad ranges of phase I and II metabolites containing hydroxylated, methoxylated, and sulfated compounds, whereas schaftoside, isoschaftoside, and vitexin underwent poor metabolism. All metabolites were identified via UHPLC-MS or UHPLC-MS/MS using compound libraries containing all conceivable metabolites. Some structures were confirmed via UHPLC-MS experiments with reference compounds after a cleavage reaction using glucuronidase and sulfatase. Of particular interest is the observed cleavage of the C–C bonds between sugar and aglycone residues in isovitexin, orientin, and isoorientin, resulting in unexpected glucuronidated or sulfated luteolin and apigenin derivatives. These findings indicate that C-glycosidic flavones can be highly metabolized in the intestine. In particular, flavonoids with ortho-dihydroxy groups showed sulfated metabolites. The identified glucuronidated or sulfated aglycones demonstrate that enzymes expressed by Caco-2 cells are able to potentially cleave C–C bonds in vitro.     

Polymorphism in single-acid triglycerides of positional and geometric isomers of octadecenoic acid

The polymorphism of 25 glycerol trioctadecenoates with double bonds ranging from Δ4-Δ17 was investigated by differential scanning calorimetry. Triglycerides withcis bonds in odd positions Δ7-Δ13 exhibited three intermediate melting (β′-) forms, but those withcis bonds in even positions, exceptcis Δ4, lacked β′-forms. Among thetrans compounds, only Δ11, 13, and 14 showed β′-forms. Thecis andtrans Δ5 triglycerides were unusual, because they readily assumed low melting (α-) forms that were not easily converted to high melting (β-) forms. β-Form mp of compounds in each series (cis ortrans) alternated depending upon double bond position; an even position correlated with high mp. Heats of fusion (ΔH_f) for β-forms, likewise, fluctuated with double bond position but nonuniformly;trans Δ6 had the highest ΔH_f (43 cal/g),cis Δ12 the lowest (21 cal/g).     

Studies on the Vilsmeier-haack reaction. Part XIII: Novel heterocyclo-substituted 4,4′-bi-pyrazolyl dithiocarbamate derivatives

5-Imino-3-methyl-l-phenyl-2-pyrazoline-4-dithiocarbamic acid (I) underwent simultaneous formylation and dimerization reactions with the Vilsmeier reagent giving 4-[5′-imino-3-(1″-formyl-2″-dimethylaminoethenyl)-3′-methyl-1′-phenyl-1′H-pyrazolo-4′-dithiocarbamyl-2,4-dihydro-3-imino-5-methyl-2-phenyl-1-pyrazoline]dithiocarbamate (II) which hydrolysed with sodium hydroxide to give 4-[3′-(1″-formyl-2″-hydroxyethenyl)-3′-methyl-1-phenyl-1′-H-pyrazolo-4′-dithiocarbamyl-1′-pyrazoline]dithiocarbamate-5,5′-dione (IV). Treatment of II and/or IV with morpholine, piperidine, piperazine, hydroxylamine, hydrazine hydrate or phenylhydrazine afforded the corresponding dipyrazolo-4,4′-dithiocarbamate derivatives with different heterocyclic systems at the 3-position. The structures of these compounds were confirmed by microanalysis data, IR and ¹H-NMR spectrometry. All synthesized compounds have been screened in vitro against Gram-positive and Gram-negative bacteria, and fungi.     

Biocatalytic detoxification of 2-chloroethyl ethyl sulfide

Rhodococcus rhodochrous IGTS8 (ATCC 53968) was shown to be capable of utilizing 2-chloroethyl ethyl sulphide (CEES) as the sole source of sulphur for microbial growth. 2-Chloroethanol and a compound tentatively identified as 2-chloroethanesulfinic acid have been detected as metabolites. This demonstrates that carbon—sulphur bonds were cleaved in CEES prior to hydrolysis of the chlorine atom. These data indicate that Rhodococcus rhodochrous IGTS8 may be useful for the biodetoxification of the chemical warfare agent mustard (2,2′ dichlorodiethyl sulphide).     

On the electrochemical behaviour in aprotic media of dihydropyridines and tetrahydrobipyridines derived from NAD+ model compounds

The electrochemical behaviour of 3-cyano-(or 3-carbamoyl-) 1-methyl-(or benzyl) 1,4-dihydropyridines (4a, b) and the corresponding 1, 1′, 4, 4′ tetrahydro-4,4′-bipyridines (5a, b) or 1, 1′, 6, 4′-tetrahydro-bipyridines (6a, b) in DMF was investigated using ac and dc voltammetrhy, cyclic voltammetry, coulometry, uv and ir spectrometry.At a vitrous carbon electrode all the compounds examined can be oxidized and reduced in a single step. The oxidation process involves loss of two electrons per molecule of reactant to give the corresponding pyridinium salt. The reduction process (which occurs at very negative potentials) involves saturation of the C₅C₆ (dihydropyridines 4a, b) and probably the C₅C₆, C_5′C_6′ (dimers 5a, b) or the C₄C₅, C_5′C_6′ (dimers 6a, b) double bonds, two and four electron per molecule, respectively, being used up.     

一株梅花鹿粪便链霉菌化学成分的分离与鉴定

对一株梅花鹿粪便链霉菌(Streptomyces sp.)的化学成分进行了分析鉴定。从链霉菌发酵液的95%乙醇提取物中分离得到6个已知化合物,分别鉴定为6-N,N-二甲基腺苷(Ⅰ)、5′-甲硫基腺苷(Ⅱ)、胸腺嘧啶脱氧核苷(Ⅲ)、环-(苯丙氨酸-羟脯氨酸)-二肽(Ⅳ)、吲哚-3-甲酸(Ⅴ)、对羟基苯乙醇(Ⅵ);6个化合物均为首次从该菌株中分离得到。     

2,5-Dialkoxysubstituierte Oligo- und Poly(1,4-phenylenethenylen)e

2,5-Dialkoxy Substituted Oligo- and Poly(1,4-phenyleneethenylene)s O-Alkylation and regioselective Rieche formylation of 2-methylhydroquinone ( 1 ) yields the 2,5-dialkoxy-4-methylbenzaldehydes 4a–j . The corresponding azomethines 5a–j enter in a strongly alkaline medium a selfcondensation reaction leading to the title compounds 6/7a–j . These conjugated oligomers and polymers possess highly regular structures with exclusively (E)-configurated double bonds. GPC, IR, ¹H-, ¹³C-NMR and MS-FD measurements were used for their characterization. Somewhat different results were obtained for the similarly prepared Schiff base 5l which contains chlorine substituents in the side chains. Cleavage of hydrogen chloride leads not only to unsaturated alkoxy groups; additionally, cyclization reactions ( 5l → 8l ) are observed.     

The Use of an Unusual Rearrangement Sequence for the Syntheses of 3‐(1‐Aminoalkylidene)‐3H‐thiophen‐2‐ones and two Examples of their Surprising Electrophilic‐Induced Dimerization Reactions

The reaction of 2‐amino‐3‐carbomethoxythiophene ( 1a ) and 2‐amino‐3‐carboethoxy‐4,5‐dimethylthiophene ( 1b ) with methyl‐ or ethylmagnesium chloride leads to new 3‐(1‐aminoalkylidene)‐3H‐thiophen‐2‐ones 4a—d in good yields (60—87%). Treatment of the compounds 4a and 4c with catalytic amounts of p‐TsOH in boiling CHCl₃ afforded the (±)‐4,4′‐bis‐(1‐aminoalkylidene)‐3′,4′‐4H,2′H‐[2,3′]bithiophenyl‐5,5′‐diones 9a and 9b as new interesting heterocycles in preparatively useful yields (60/mdash;65%).     

Identification and Binding Characterization of Three Odorant Binding Proteins and One Chemosensory Protein from Apolygus lucorum (Meyer-Dur)

For the sucking insect, Apolygus lucorum, taste is essential for finding host plants and oviposition sites. In A. lucorum, taste relies largely on the sensory system located within its proboscis. In this study, we constructed a cDNA library from A. lucorum proboscises and conducted preliminary analysis of 1554 ESTs. From this collection, we identified three putative odorant-binding proteins (AlucOBP3, AlucOBP4, AlucOBP6) and one chemosensory protein (AlucCSP1). Quantitative real-time polymerase chain reaction (qPCR) was used to study the expression pattern of these four genes. All four were expressed mainly in antennae, proboscises and legs, suggestive of roles in olfaction and gustation. We expressed and purified recombinant versions of AlucOBP3, AlucOBP4, AlucOBP6, and AlucCSP1 in a prokaryotic expression system. The ligand-binding specificities of the four proteins then were investigated in competition assays using 4,4′-dianilino-1,1′-binaphthyl-5, 5′-sulfonic acid (bis-ANS) as a probe. Of the 58 small organic compounds and five cotton secondary metabolites tested, plant volatiles cannot effectively displace bis-ANS from any of the four proteins. In contrast, most of the cotton secondary metabolites have high affinities for the three OBPs and AlucCSP1, indicating that these binding proteins more likely play a role in gustation than in olfaction.     

Quick Click: The DNA‐Templated Ligation of 3′‐O‐Propargyl‐ and 5′‐Azide‐Modified Strands Is as Rapid as and More Selective than Ligase

The copper(I)‐mediated azide–alkyne cycloaddition (CuAAC) of 3′‐propargyl ether and 5′‐azide oligonucleotides is a particularly promising ligation system because it results in triazole linkages that effectively mimic the phosphate–sugar backbone of DNA, leading to unprecedented tolerance of the ligated strands by polymerases. However, for a chemical ligation strategy to be a viable alternative to enzymatic systems, it must be equally as rapid, as discriminating, and as easy to use. We found that the DNA‐templated reaction with these modifications was rapid under aerobic conditions, with nearly quantitative conversion in 5 min, resulting in a k_obs value of 1.1 min^?1, comparable with that measured in an enzymatic ligation system by using the highest commercially available concentration of T4 DNA ligase. Moreover, the CuAAC reaction also exhibited greater selectivity in discriminating C:A or C:T mismatches from the C:G match than that of T4 DNA ligase at 29 °C; a temperature slightly below the perfect nicked duplex dissociation temperature, but above that of the mismatched duplexes. These results suggest that the CuAAC reaction of 3′‐propargyl ether and 5′‐azide‐terminated oligonucleotides represents a complementary alternative to T4 DNA ligase, with similar reaction rates, ease of setup and even enhanced selectivity for certain mismatches.