Elastic scattering and rotational excitation of nitrogen molecules by sodium atoms

A quantal study of the rotational excitation of nitrogen molecules by sodium atoms is carried out. We present the two-dimensional potential energy surface of the NaN(2) complex, with the N(2) molecule treated as a rigid rotor. The interaction potential is computed using the spin unrestricted coupled-cluster method with single, double, and perturbative triple excitations (UCCSD(T)). The long-range part of the potential is constructed from the dynamic electric dipole polarizabilities of Na and N(2). The total, differential, and momentum transfer cross sections for rotationally elastic and inelastic transitions are calculated using the close-coupling approach for energies between 5 cm(-1) and 1500 cm(-1). The collisional and momentum transfer rate coefficients are calculated for temperatures between 100 K and 300 K, corresponding to the conditions under which Na-N(2) collisions occur in the mesosphere.     

Nonribosomal peptide synthesis in animals: the cyclodipeptide synthase of Nematostella

Cyclodipeptide synthases (CDPSs) are small enzymes structurally related to class-I aminoacyl-tRNA synthetases (aaRSs). They divert aminoacylated tRNAs from their canonical role in ribosomal protein synthesis, for cyclodipeptide formation. All the CDPSs experimentally characterized to date are?bacterial. We show here that a predicted CDPS from the sea anemone Nematostella vectensis is an active CDPS catalyzing the formation of various cyclodipeptides, preferentially containing tryptophan. Our findings demonstrate that eukaryotes encode active CDPSs and suggest that all CDPSs have?a similar aminoacyl-tRNA synthetase-like architecture and ping-pong mechanism. They also raise questions about the biological roles of the cyclodipeptides produced in bacteria and eukaryotes.     

Structural variability of endotoxins from R-type isogenic mutants of Shigella sonnei

The structural variations in the rough-type endotoxins [lipopolysaccharides (LPSs)] of Shigella sonnei mutant strains (S. sonnei phase II-4303, R41, 562H and 4350) were investigated by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem MS. A series of S. sonnei mutants had previously been the subject of analytical studies on the biosynthesis of heptose components in the core oligosaccharide region of LPSs. This study gives a complete overview on the structures of the full core and lipid A of S. sonnei mutant strains by MS. We found that the LPSs of the isogenic rough mutants were formed in a step-like manner containing 0:1:2:3 heptose in the deep core region of 4350, 562H, R41 and 4303, respectively, and the longest LPS from the mutant S. sonnei 4303 contained also five hexoses. The structural variations in the lipid A moiety and in the oligosaccharide part of the intact LPS were followed by MALDI-TOF-MS/MS. For the dissolution and the ionization of the samples, 2,5-dihydroxybenzoic acid in citric acid solution was applied as matrix. The detailed evaluation of the mass spectra indicates heterogeneity in the lipid part due to the differences in the phosphate and fatty acid composition.     

Synthesis and in vitro antiproliferative activity of novel androst-5-ene triazolyl and tetrazolyl derivatives

A straightforward and reliable method for the regioselective synthesis of steroidal 1,4-disubstituted triazoles and 1,5-disubstituted tetrazoles via copper(I)-catalyzed cycloadditions is reported. Heterocycle moieties were efficiently introduced onto the starting azide compound 3β-acetoxy-16β-azidomethylandrost-5-en-17β-ol through use of the "click" chemistry approach. The antiproliferative activities of the newly-synthesized triazoles were determined in vitro on three human gynecological cell lines (HeLa, MCF7 and A2780) using the microculture tetrazolium assay.     

Exploring and characterizing the folding processes of Lys- and Arg-containing Ala-based peptides: a molecular dynamics study

In this study, molecular dynamics simulations were carried out on Lys- and Arg-containing Ala-based peptides (i.e. Ace-(AAAAK)(n)A-NH(2) and Ace-(AAAAR)(n)A-NH(2), where n=1-4), in order to explore and characterize their folding processes. For the oligopeptides, the evolution of α-helical structure with regard to the whole conformation, as well as to each residue was investigated, and the helix-forming propensities were characterized. On the basis of the helicity curves, representing the alteration of average helicity as a function of time, the typical time values describing the folding processes and subprocesses were identified. In the case of each peptide, the evolution and role of helix-stabilizing, non-local and side-chain-to-backbone H-bonds were examined. The appearing i←i+4 H-bonds pointed out the role of these interactions in the stabilization of α-helical conformations, while the occurring i←i+3 H-bonds indicated the presence of β-turn or 3(10)-helical structures. Studying the formation and role of non-local and side-chain-to-backbone H-bonds led to the observation that these types of interactions produced an effect on the evolution of helical conformations, as well as on the folding processes.     

Efficient approach to novel 1α-triazolyl-5α-androstane derivatives as potent antiproliferative agents

Stereoselective 1,4-Michael addition of azoimide to 17β-acetoxy-5α-adrost-1-en-3-one was carried out to furnish a 1α-azido-3-ketone, which was reduced to give the 3β- and 3α-hydroxy epimers in a ratio of 5 : 2. The Cu(I)-catalyzed 1,3-dipolar cycloaddition of the major isomer to terminal alkynes afforded 1α-triazolyl derivatives, which were deacetylated to the corresponding 3β,17β-diols or oxidized to the analogous 3-ketones. However, the ability of the minor 1α,3α-azidoalcohol to undergo similar cyclization was found to be affected significantly by the steric bulk of the substituents on the alkyne reaction partner. All triazolyl compounds were tested in vitro on three malignant gynecological cell lines (HeLa, MCF7 and A2780).     

Elaboration of vinblastine hybrids using a reactive in situ generated N-carboxyanhydride

Hybrids of vinblastine and phomopsin, designed by a molecular modelling study, were elaborated in order to target tubulin. The key step of the synthesis (fragmentation and insertion of vindoline) was mediated by an internal N-carboxyanhydride (or O-acylcarbamate). This reaction was diastereospecific and addition of silver salts could reverse the diastereoselectivity. Even if the synthesized compounds are inactive, this synthesis represents an original example of a C-N fragmentation mediated by a N-carboxyanhydride.     

Nitrogen heteroaromatic cations by [2+2+2] cycloaddition

A modular approach to the construction of monocationic quaternary N-heteroaromatic frameworks was developed capitalizing on a direct pyridine-type nitrogen quaternization followed by metal-catalyzed [2+2+2] cycloaddition with gaseous acetylene. The flexibility of the route is demonstrated on 12 diverse scaffolds based on pyridinium, quinolinium, thiazolium, benzothiazolium, imidazolium, and pyrimidinium. Electrochemical study revealed a quinolinium redox system with two electrochemically distinct forms that are interconverted by a homogeneous chemical reaction triggered by fast electron transfers (reduction at -0.7 V and oxidation at -0.05 V).     

Electronic and geometrical manipulation of the excited state of bis-terdentate homo- and heteroleptic ruthenium complexes

This work describes the synthesis and characterization of two new bis-terdentate Ru(II) complexes. Compound 1 is a homoleptic complex containing two CNC N-heterocyclic carbene (NHC) based ligands, whereas compound 2 bears one CNC ligand and an ancillary terpyridine ligand. The redox and photophysical properties of both compounds have been investigated and their X-ray crystal structures determined. Complex 1 displays a close-to-perfect octahedral coordination geometry and is not luminescent at room temperature while complex 2 features room temperature and 77 K luminescence despite its partially distorted geometry. The presence of the NHC moieties brings a significant amount of electronic density to the metal centre therefore lowering its oxidation potential with respect to that of analogous polypyridyl complexes.     

Complexation of tauro- and glyco-conjugated bile salts with α-cyclodextrin and hydroxypropyl-α-cyclodextrin studied by affinity capillary electrophoresis and molecular modelling

The interaction of the bile salts taurocholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate, and glycochenodeoxycholate present in man, dog, and rat with α-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin was investigated by mobility shift affinity capillary electrophoresis. The cyclodextrins are applied as excipients for solubilisation of drug substances with poor aqueous solubility. Accurate determination of stability constants is challenging for weak analyte-ligand interactions such as the conjugated bile salt α-cyclodextrin interactions. A new approach for correction of medium effects due to the high additive concentrations in the background electrolyte was introduced. The use of prostaglandin A(1) as an interacting marker molecule offered a more satisfactory approach for correction than the commonly employed methods based on viscosity or current ratios. The interacting marker was chosen over a non-interacting marker to avoid the difficult validation of the non-interacting properties. The investigated bile salts all interacted with α-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin. Stability constants ranging from 14 to 95 M(-1) were obtained with slightly higher affinities toward the substituted cyclodextrin. Molecular modelling demonstrated that the interaction between the two species involves the side chain of the bile salt. All together, these results indicate minor bile salt-mediated displacement of substances from α-cyclodextrin complexes in the small intestine.