Cis-Cycloprolylprolin-Anion-ein konfigurationsstabiles Carbanion

The racemisation ofcyclo-(l-Pro?l-Pro) (2) with metal amides in liq. ammonia was examined. The K-kation causes more extensive racemisation than Na-kation, which in turn is more effective than Li⁺. This, the racemisation of2 int-butyl alcohol with K⁺C₆H₅O^? and the data gained from corresponding deuterated medium show that the racemisation of2 proceeds in two steps: in the first, the less stabletrans-cyclo-(l-Pro?d-Pro) (3) is formed, followed by the rapid conversion of3 to a mixture ofcyclo-(l-Pro?l-Pro) andcyclo-(d-Pro?d-Pro) in the second step.     

Chiral resolution of l- and d-alanine and a racemic macrocyclic nickel(II) complex: synthesis and crystal structures

The reactions of a racemic four-coordinate Ni(II) complex [Ni(rac-L)](ClO₄)₂ with l- and d-alanine in acetonitrile/water gave two six-coordinate enantiomers formulated as [Ni(RR-L)(l-Ala)](ClO₄)·2CH₃CN (1) and [Ni(SS-L)(d-Ala)](ClO4) (2) (L = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclo-tetradecane, Ala^? = alanine anion), respectively. Evaporation from the remaining solutions gave two four-coordinate enantiomers characterized as [Ni(SS-L)](ClO₄)₂ (S-3) and [Ni(RR-L)](ClO₄)₂ (R-3), respectively. Single-crystal X-ray diffraction analyses of complexes 1 and 2 revealed that the Ni(II) atom has a distorted octahedral coordination geometry, being coordinated by four nitrogen atoms of L in a folded configuration, plus one carboxylate oxygen atom and one nitrogen atom of l- or d-Ala^? in mutually cis-positions. Complexes 1 and 2 are supramolecular stereoisomers, constructed via hydrogen bonding between [Ni(RR-L)(l-Ala)]⁺ or [Ni(SS-L)(d-Ala)]⁺ monomers to form 1D hydrogen-bonded zigzag chains. The homochiral natures of complexes 1 and 2 have been confirmed by CD spectroscopy.     

Computational investigation of thermochemical properties of non-natural C-nucloebases: different hydrogen-bonding preferences for non-natural Watson–Crick base pairs

In the present density functional theory study, we have compared intrinsic properties of non-natural nucleobases (acA, acG, acC, and acT nucleobases) such as proton affinities, gas phase acidities, tautomerization, and hydrogen-bonding properties with those in normal Watson–Crick nucleobases (A, G, C, T nucleobases). The hydrogen-bonding interactions in non-natural and Watson–Crick base pairs were studied at B3LYP/6-311++G (d,p) level regarding their geometries, energies, and topological features of the electron density. The quantum theory of atoms-in-molecule (QTAIM) and natural bond orbital (NBO) analyses were employed to elucidate the interaction characteristics in base pairs. The electron density ρ(r) as well as its Laplacian $ \nabla^{2} $ ρ(r) at the hydrogen bond critical point predicted by QTAIM is strongly correlated with hydrogen bond structural parameter and the second-order perturbation energies in NBO scheme. Our results show that most of hydrogen bonds in normal Watson–Crick and non-natural base pairs must be considered as electrostatic interactions. Results of calculations revealed that energetic values of hydrogen bonds in T–A base pair are more than those in ac T–ac A base pair, while values of hydrogen bonds in C–G base pair and ac C–ac G base pair are almost the same. These results confirmed stability order of stabilization energies of these base pairs.     

Lipopolysaccharides of marine blue-green algae

The lipopolysaccharides (LPSs) have been isolated from two blue-green algae,Oscillatoria hilderbrandtii andNostoc sp. by the method of phenol-water extraction. The LPSs contain polysaccharide and lipid components. The polysaccharide fraction fromO. hildebrandtii consists predominantly of 1,3-bound rhamnose residues with a substituent in the second position. The rhamnose residues in the polysaccharide fraction ofNostoc are connected by 1,3- and 1,2-glycosidic bonds. The lipid components of the LPSs fromO. hilderbrandtii andNostoc consist of palmitic and steric acids, with glucosamine and glucose.     

Neutral diterpenoids of oleoresins of five species of conifers of Transcarpathia

The compositions of the neutral diterpenoids of the oleoresins of five species of conifers growing in the Transcarpathia have been studied. It has been found that the oleoresins ofAbies alba M.,Larix decidua M., andPicea excelsa L. contain more than 50% of neutral diterpenoids. The group and qualitative compositions of the oxygen-containing diterpenoids have been determined. In the oleoresins ofAbies alba,Picea excelsa, andPicea abies tertiary alcohols — cis-abienol and isocembrol — predominate, while inLarix decidua the main component is the hydroxy ester larixyl acetate. Primary alcohols related to the resin acids have been found in all the oleoresins investigated. Features of the distribution of diterpenoids according to the species of conifers have been revealed. The results obtained are necessary for the chemotaxonomy of conifers of the family Pinceae.     

One enantiomeric fluorescent sensor pair to discriminate four stereoisomers of threonines

The BINOL-amino alcohol enantiomeric pair(S)-1 and(R)-1 are discovered to conduct both enantioselective and diastereoselective fluorescent discrimination of the four stereoisomers of threonine derivatives.This study utilizes different fluorescence responses of one sensor at two emission wavelengths toward the stereoisomeric substrates which expands the capability of the sensor in chiral recognition.In addition,the sensor pair also allows visual recognition of the N-protected L-allo-threonine and D-allo-threonine by enantioselective precipitation.     

Size-dependent core-level spectroscopy of free neutral clusters

Studies of the electronic and geometric structure of free clusters are presented to highlight the application of core-level spectroscopy using synchrotron radiation to cluster physics. The study of electronic structure deals with the excitation of the C 1s electron to the Rydberg states of the molecule in CH₄ clusters and demonstrates the gradual evolution of the surface and bulk-specific spectral features with cluster size. A second study investigates the K-edge excitations in Ne clusters and is concerned with extracting structural information from the X-rays Absorption Near-Edge Structure (XANES).     

Gas-chromatographic determination of the composition of the volatile components of the oleoresins of some species of conifers

Using the method of analytical GLC in a glass capillary column, the compositions have been studied of the volatile fractions of the oleoresins of five species of conifers:Larix decidua,Pinus strobus,Pinus mugo,Picea excelsa, andPinus abies. In the oleoresins 21 monoterpene and 22 sesquiterpene compounds were identified from their relative retention times and with the aid of additives. The main components of the volatile fractions of the oleoresins were α- and β-pinenes and 3-carene among the monoterpenes, and longifolene caryophyllene, δ- and γ-cadinenes and α-murolene among the sesquiterpene compounds. The quantitative analysis of the fractions was carried out by the method of internal normalization from averaged correlation coefficients.     

Alkaloids of Rauwolfia species growing in Vietnam

Reserpine, ajmaline, serpentine, ajmalicine, isoreserpiline, and other alkaloids have been isolated from the roots ofRauwolfia cambodiana Pierre ex Pitard,R. verticillata Baill. andR. serpentina Benth.R. vomitoria Afz. was the richest in alkaloids.     

Stereoselective (exo-specific) synthesis, dynamic 1H NMR and quantum chemical conformational and configurational analysis of norbornene-aziridine-E-imidoyl system

Stereoselective (exo-specific) synthesis, dynamic ¹H NMR and computational analysis of exo-N??-{3-azatricyclo[3.2.1.0.^2,4]oct-3-yl)mesithyloxy)methylene}-1-benzensulfunamide (3) were investigated. Aziridine nitrogen inversion gives rise to two sets of configurations where the N-substituent is Syn (S) or Anti (A) to C7 of the norbornyl ring. At lower temperature, the proton signals of aziridine exo-E-3 decoalesces to show two syn conformers and one anti conformer (exo-E-3 ^{1 S} ? $ \leftrightharpoons $ ?exo-E-3 ^{2 S} ? $ \leftrightharpoons $ ?exo-E-3 ^{3 A} ) with ratio of 60:20:20, respectively. Experimentally, the Gibbs free energy of activations [??G ^? (kcal/mol) ?±?0.08] were calculated 11.96, 12.45 for 3 isomerizations. The standard Gibbs free energy (??G ^o kcal/mol) 0.174, 0, 0.174, and 0.298 at 213?K and energy minimum 6.64, 4.77 and 1.78 were calculated for 3 ^1S? $ \leftrightharpoons $ ?3 ^2S, 3 ^2S? $ \leftrightharpoons $ ?3 ^{3 A} , 3 ¹ S? $ \leftrightharpoons $ ?3 ^{3 A} isomerizations, respectively. The enthalpy (??H ^?, kcal/mol) and entropy (??S ^?, cal?mol^?1?K^?1) of activation for the nitrogen inversion of aziridine of 3 were calculated 11.2 and ?0.80, respectively.     

A novel view of modelling interactions between synthetic and biological polymers via docking

Multipoint interactions between synthetic and natural polymers provide a promising platform for many topical applications, including therapeutic blockage of virus-specific targets. Docking may become a useful tool for modelling of such interactions. However, the rigid docking cannot be correctly applied to synthetic polymers with flexible chains. The application of flexible docking to these polymers as whole macromolecule ligands is also limited by too many possible conformations. We propose to solve this problem via stepwise flexible docking. Step 1 is docking of separate polymer components: (1) backbone units (BU), multi-repeated along the chain, and (2) side groups (SG) consisting of functionally active elements (SG _F ) and bridges (SG _B ) linking SG _F with BU. At this step, probable binding sites locations and binding energies for the components are scored. Step 2 is docking of component-integrating models: [BU] _m , SG = SG _F –SG _B , BU–SG, BU–BU(SG)–BU, BU(SG)–[BU] _m –BU(SG), and [BU _var (SG _var )] _m . Every modelling level yields new information, including how the linkage of various components influences on the ligand—target contacts positioning, orientation, and binding energy in step-by-step approximation to polymeric ligand motifs. Step 3 extrapolates the docking results to real-scale macromolecules. This approach has been demonstrated by studying the interactions between hetero-SG modified anionic polymers and the N-heptad repeat region tri-helix core of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41, the key mediator of HIV-1 fusion during virus entry. The docking results are compared to real polymeric compounds, acting as HIV-1 entry inhibitors in vitro. This study clarifies the optimal macromolecular design for the viral fusion inhibition and drug resistance prevention.     

Copolymer-grafted silica phase from a cation–anion monomer pair for enhanced separation in reversed-phase liquid chromatography

This work reports a new imidazolium and l-alanine derived copolymer-grafted silica stationary phase for ready separation of complex isomers using high-performance liquid chromatography (HPLC). For this purpose, 1-allyl-3-octadecylimidazolium bromide ([AyImC₁₈]Br) and N-acryloyl-l-alanine sodium salt ([AAL]Na) ionic liquids (IL) monomers were synthesized. Subsequently, the bromide counteranion was exchanged with the 2-(acrylamido)propanoate organic counteranion by reacting the [AyImC₁₈]Br with excess [AAL]Na in water. The obtained IL cation–anion monomer pair was then copolymerized on mercaptopropyl-modified silica (Sil-MPS) via a surface-initiated radical chain-transfer reaction. The selective retention behaviors of polycyclic aromatic hydrocarbons (PAHs), including some positional isomers, steroids, and nucleobases were investigated using the newly obtained Sil-poly(ImC₁₈-AAL), and octadecyl silylated silica (ODS) was used as the reference column. Interesting results were obtained for the separation of PAHs, steroids, and nucleobases with the new organic phase. The results showed that the Sil-poly(ImC₁₈-AAL) presented multiple noncovalent interactions, including hydrophobic, π–π, carbonyl–π, and ion–dipole interactions for the separation of PAHs and dipolar compounds. Only pure water was sufficient as the mobile phase for the separation of the nucleobases. Ten nucleosides and bases were separated, using only water as the mobile phase, within a very short time using the Sil-poly(ImC₁₈-AAL), which is otherwise difficult to achieve using conventional hydrophobic columns such as ODS. The combination of electrostatic and hydrophobic interactions are important for the effective separation of such basic compounds without the use of any organic additive as the eluent on the Sil-poly(ImC₁₈-AAL) column.

Isoform specific gene auto-regulation via miRNAs: a case study on miR-128b and ARPP-21

In this study, we investigate whether miRNAs located within “host” protein-coding genes may regulate the expression of their host genes. We find that 43 of 174 miRNAs encoded within RefSeq genes are predicted to target their host genes. Statistical analysis of this phenomenon suggests that gene auto-regulation via miRNAs may be under positive selective pressure. Our analysis also indicates that several of the 43 miRNAs have a much lower expectation of targeting their host genes by chance than others. Among these examples, we identify miR-128b:ARPP-21 (cyclic AMP-regulated phosphoprotein, 21 kD) as a case in which both the miRNA and the target site are also evolutionarily conserved. We provide experimental support for this miRNA:target interaction via reporter silencing assays, and present evidence that this isoform-specific gene auto-regulation has been preserved in vertebrate species in order to prevent detrimental consequences of ARPP-21 over-expression in brain.     

Exploiting thermodynamic data to optimize the enantioseparation of underivatized amino acids in ligand exchange capillary electrophoresis

Stereoselective amino acid analysis has increasingly moved into the scope of interest of the scientific community. In this work, we report a study on the chiral separation of underivatized d,l-His by ligand exchange capillary electrophoresis (LECE), utilizing accurate ex ante calculations. This has been obtained by the addition to the background electrolytes (BGE) of NaClO₄ which renders the separations “all in solution processes”, allowing to accurately calculate in advance the concentrations of the species present in solution and to optimize the system performances. To this aim, the formation of ternary complexes of Cu²⁺ ion and l-lysine (l-Lys) or l-ornithine (l-Orn) with l- and d-histidine (His), and histamine (Hm) have been studied by potentiometry and calorimetry at 25 °C and with 0.1 mol dm^?3 (KNO₃) in aqueous solution. The ternary species [Cu(L)(l-His)H]⁺ and [Cu(L)(d-His)H]⁺ (where L?=?l-Lys or l-Orn) show a slight but still detectable stereoselectivity, and the determination of ΔH° and ΔS° values allowed the understanding of the factors which determine this phenomenon. The stereoselectivity showed by the protonated ternary species has been exploited to chirally separate d,l-His in LECE, by using the binary complexes of copper(II) with l-Lys or l-Orn as background electrolytes added with the appropriate amounts of NaClO₄.

Pentaketide metabolites of mutants and the biosynthesis of melanin inVerticillium tricorpus

From mutants of the fungusVerticillium tricorpus Isaac., having various genetic blocks in the biosynthesis of melanin, we have isolated and identified scytalone, flaviolin, 3,3′-biflavinolin, 2-hydroxyjuglone, vermelone, and 1,8-dihydroxynaphthalene, which, in combination with the results of complementation analysis, has enabled the main stages of the biosynthesis of melanin inV. tricorpus to be established. The results on the inhibition of the biosynthesis of melanin by tricyclazole in natural isolates ofV. tricorpus indicates that the initital stages of the biosynthesis of melanin inV. tricorpus up to the formation of 1,3,8-trihydroxynaphthalene are identical with those ofVerticillium dahliae.     

Carbohydrate recognition of symmetrical tripodal receptor type tris(2-aminoethyl)amine derivatives

Carbohydrate recognition of some bioactive symmetrical tripodal receptor type tris(2-aminoethyl)amine (TAEA) derivatives was investigated. In calorimetric experiments, the highest binding constant (Ka) of compound C (C₃₅H₄₉N₅O₄S) with methyl α-d-mannopyranoside was Ka = 858 M^?1 with 1:1 stoichiometry. Formation of hydrogen bonds in binding between symmetrical tripodal receptor type compound C and sugars was suggested by the large negative values of ?H° (=?34 to ?511 kJ mol^?1). In a comparison of each set of α- and β-anomers of some monosaccharides (methyl α/β-d-galactopyranoside, methyl α/β-d-glucopyranoside, and methyl α/β-l-fucopyranoside), compound C showed that the binding constant of β-anomer was larger than that of the corresponding α-anomer, indicating higher β-anomer selectivity. The calculated energy-minimized structure of the complex of compound C with guest methyl α-d-mannopyranoside is also presented. The experimental results obtained from this work indicated that symmetrical tripodal receptor type TAEA derivative C has a lectin-like carbohydrate recognition property.     

Synthesis and antimicrobial of some new substituted tetrazolomethylbenzo[d]-[1,2,3]triazole derivatives using 1H-benzo[d][1,2,3]triazole as starting material

A series of tetrazolomethylbenzo[d][1,2,3]triazole derivatives (2–14) have been synthesized and evaluated as antimicrobial agents from 1H-benzo[d][1,2,3]triazole (1) as starting material. The reaction of benzotriazole 1 with chloroacetonitrile afforded 2-(1H-benzo[d][1,2,3]-triazol-1-yl)acetonitrile 2, which was reacted with sodium azide to give tetrazole derivative 3. Esterification of benzotriazole 1 with ethyl bromoacetate in the presence of anhydrous potassium carbonate afforded ester 4, which was treated with hydrazine hydrate to afford the corresponding hydrazide 5. Reaction of 3 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide afforded the nitro-glycoside derivative 6, which was deacetylated using methanolic ammonia to deprotected nitroglycoside 7. The hydrazide 5 was reacted with 4,5,6,7-tetrachlorophthalic anhydride or 1,2,4,5-benzenetetracarboxylic dianhydride in refluxing glacial acetic acid to give the corresponding imides 8 and 9, respectively. Also, the hydrazide 5 was reacted with carbon disulphide in ethanol to give potassium salt 10, which was reacted with hydrazine hydrate to afford aminotriazole derivative 11. The latter compound was reacted with carbon disulphide to afford thiadiazole derivative 12, which was treated with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide to give the thioglycoside derivative 13. Deacetylation of the thioglycoside 13 using methanolic ammonia solution at room temperature afforded the deprotected thioglycoside 14. The antimicrobial screening of some synthesized compounds showed that many of these compounds have good antimicrobial activities comparable to streptomycin and fusidic acid as reference drugs.     

Synthesis, X-ray structural analysis, and cytotoxic activity of some new androstane d-homo lactone derivatives

A series of d-homo lactones 4?C10 from dehydroepiandrosterone 1 via 16-hydroximino derivatives 2 and 3 were synthesized. The d-homo lactone 4 was transformed by the Oppenauer oxidation to obtain compound 5. The (Z)-2-hydroxymethylene-4-en-3-one compound 6, was obtained through reaction of 4-en-3-one compound 5 with ethyl formate and sodium hydride. The epoxides 8 and 9 were prepared from compound 7 by oxidation with m-chloroperbenzoic acid. Compound 10 was obtained by treating epoxides 8 and 9 with chromium(VI)-oxide. The structure of compounds 6 and 10 were confirmed by X-ray structural analysis. These derivatives were screened for antitumor activity against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER?, MDA-MB-231, prostate cancer AR?, PC-3), and one human non-tumor cell line, MRC-5. Compounds 4, 7, 8, and 10 exhibited significant antitumor activity against MDA-MB-231 cells, while compound 5 showed strong cytotoxicity against MDA-MB-231. No compounds displayed toxicity against MRC-5 cells.     

Interactions of some protonated α-amino acid methyl esters with hexaethyl p-tert-butylcalix[6]arene hexaacetate in nitrobenzene saturated with water

The exchange extraction constants corresponding to the general equilibrium C⁺(aq) + 1·Cs⁺(nb) ? 1·C⁺ (nb) + Cs⁺(aq) occurring in the two-phase water–nitrobenzene system (C⁺ = protonated α-amino acid methyl ester, 1 = hexaethyl p-tert-butylcalix[6]arene hexaacetate; aq = aqueous phase, nb = nitrobenzene phase) were evaluated on the basis of extraction experiments and γ-activity measurements. Further, the stability constants of the 1·C⁺ cationic complex species in nitrobenzene saturated with water were calculated; they were found to increase in the following cation order: protonated l-tryptophan methyl ester < protonated l-phenylalanine methyl ester < protonated l-leucine methyl ester < protonated l-methionine methyl ester < protonated l-valine methyl ester.     

Complexation of trimeric copper(i) and silver(i) 3,5-bis(trifluoromethyl)pyrazolates with amine-borane

A complexation of trimeric copper(i) and silver(i) 3,5-bis(trifluoromethyl)pyrazolates ((ML)₃) with BH₃NEt₃ was studied by IR spectroscopy in hexane and dichloromethane solutions. In hexane, two complexes [(ML)₃][BH₃NEt₃]₂ (1) and [(ML)₃][BH₃NEt₃] (2) were formed depending on the ratio of reagents. In dichloromethane, only one complex [(ML)₃][BH₃NEt₃] (2) was found. The thermodynamic parameters (ΔH ^○, ΔS ^○) of complex 1 in hexane and complex 2 in dichloromethane were obtained. The complex [(AgL)₃][BH₃NEt₃] was isolated in the solid state, its structure was established by X-ray diffraction. The complex is formed due to two bridges B-H-Ag, one BH group is not involved in the complexation. In crystal, molecules 2 form supramolecular dimers due to the intermolecular interactions between metals of two macrocycles.