Efficient chemical synthesis of a dodecasaccharidyl lipomannan component of mycobacterial lipoarabinomannan

Lipomannan (LM) is one of the domains of lipoarabinomannan (LAM) glycolipids, the latter being one of several cell surface organic molecules that fortify mycobacterial species against external attack. Some members of mycobacterial families are pathogenic, most notably Mycobacterium tuberculosis and Mycobacterium leprae, while others are nonpathogenic, and used in the clinic, such as Mycobacterium smegmatis. Additional biological significance arises from the fact that LM has been implicated in several health disorders outside of those associated with mycobacterial pathogens, notably for treatment of bladder cancer. LM is comprised of a heavily lipidated phosphoinositide dimannoside headgroup, from which a mannan array, of varied complexity, extends. The latter consists of a 1,6-alpha-linked backbone flanked at position O2, not necessarily regularly, with alpha-linked mannosides. This paper gives an example of lipomannan synthesis in which all of the sugar components, whether functioning as donors or acceptors, are obtained from n-pentenyl orthoesters, themselves in turn prepared in three easy steps from D-mannose. Assembly of the mannan array is facilitated by the exquisite regioselectivity occasioned by the use of ytterbium triflate/N-iodosuccinimide as the trigger for reaction of n-pentenyl orthoesters.     

Use of combinatorial library screening to identify inhibitors of a bacterial two-component signal transduction kinase

Bacterial resistance to antibiotics is emerging as amajor concern to the medical community. Theappearance of several antibiotic-resistant strains,including multidrug-resistant Staphylococcusaureus, raises the prospect that infections by thesebacteria could soon become untreatable with currentlyavailable antibiotics. In order to address thisproblem, increased emphasis is being placed on thediscovery of novel classes of antibacterial agentsthat inhibit novel molecular targets using sources ofcompounds not yet exploited for antibiotic drugdiscovery. Novel classes of compounds can now berapidly investigated using combinatorial chemistryapproaches. This report describes the identificationof novel antibacterial compounds from a combinatoriallibrary of N-acetylated, C-amidated D-amino acidhexapeptides. This library of compounds was screenedfor inhibitors of CheA, a member of the bacterialtwo-component signal transduction kinase family. Several peptides with apparent IC₅₀ values in thelow micromolar range were identified. In addition toinhibiting CheA, these peptides inhibited mammalianprotein kinase C (from rat brain) with comparablepotency. Finally, these peptides were also found tohave significant antibacterial properties, althoughthe true mechanism by which they exhibited inhibitionof bacterial growth remains uncertain.     

Synthesis, spectroscopy and cyclic voltammetry of new iron(III) complexes with 5-methyl-3-formyl pyrazole 3-hexamethyleneiminyl thiosemicarbazone (HMPz3Hex): X-ray crystallographic identification of [Fe(MPz3Hex)2]ClO4 · 2H2O with an indication for unusual rotation about the azomethine double bond on complexation with iron(III)

New iron(III) complexes of 5-methyl-3-formylpyrazole 3-hexamethyleneiminylthiosemicarbazone (HMPz3Hex), [Fe(MPz3Hex)₂]X · nH₂O (where X = Cl, NO₃or ClO₄ and n = 1–2) have been synthesized and physico-chemically characterized by magnetic data (polycrystalline state), electronic, i.r. and e.p.r. spectral studies. The reported complexes are all cationic electrolytes (1:1) containing two moles of monodeprotonated title ligand and an anionic counterpart. I.r. spectra (4000–200 cm^?1) indicate coordination to the central iron(III) ion via the pyrazolyl (tertiary) ring nitrogen, azomethine nitrogen and thiolato sulphur atoms of the primary ligand molecule. E.p.r. data (r.t. and l.n.t.) show the presence of a low-spin iron(III) cation with d _xz ² d _xz ² d _xz ¹ configuration. Cyclic voltammograms of iron(III) complexes indicate a reversible Fe⁺³/Fe⁺² couple. X-ray data of [Fe(MPz3Hex)₂]ClO₄ · 2H₂O (P₁, triclinic) authenticate a FeN₄S₂ distorted octahedral coordination with the two azomethine nitrogens trans to each other; the pyrazolyl nitrogens and thiolato sulphurs are in cis-positions, indicating an unusual rotation about the azomethine (C=N) double bond of the free HMPz3Hex during complexation with iron(III).     

Peptide Conjugates of a Nonsteroidal Anti‐Inflammatory Drug as Supramolecular Gelators: Synthesis,Characterization, and Biological Studies

Indomethacin ( IND ), which is a well‐known nonsteroidal anti‐inflammatory drug (NSAID), was conjugated with various naturally occurring amino acids. Most of these bioconjugates were capable of gelling pure water, a solution of NaCl (0.9 wt %), and phosphate‐buffered saline (pH 7.4), as well as a few organic solvents. The gels were characterized by table‐top and dynamic rheology, and electron microscopy. Variable‐temperature ¹H NMR spectroscopy studies on a selected gel were performed to gain insights into the self‐assembly process during gel formation. Both 1D and 2D hydrogen‐bonded networks were observed in the single‐crystal structures of two of the gelators. Plausible biological applications of the hydrogelators were evaluated with the ultimate aim of drug delivery in a self‐delivery fashion. All hydrogelators were stable in phosphate‐buffered saline at pH 7.4 at 37 °C, and biocompatible in mouse macrophage RAW 264.7 cell line (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay). Two of the most biocompatible hydrogelators displayed an anti‐inflammatory response comparable to that of the parent drug IND in prostaglandin E₂ assay. Release of the bioconjugates into the bulk solvent interfaced with the corresponding hydrogels indicated their plausible future application in drug delivery.     

13,13a‐Di­hydro‐13‐methoxy‐9‐methyl‐1‐benzo­pyrano­[4,3‐i]­dinaphtho­[2,1‐c;1′,2′‐f]‐2,8‐dioxa­bicyclo­[3.3.1]­nonane

The crystal structure of the title compound, C₃₂H₂₄O₄, contains three fused di­hydro­pyran rings (A, B and C); ring A is fused with a benzene ring while the other two rings, B and C, are fused with naphthalene rings. Ring A adopts a half‐chair conformation with an equatorial methoxy group, whereas ring B assumes a distorted half‐chair conformation, the A/B ring junction being trans. Ring C adopts a distorted half‐boat conformation and is nearly orthogonal to ring B. Ring C is inclined to the best plane of ring A at an angle of 112.1 (1)°.     

Modeling and simulation of long-wave infrared InAs/GaSb strained layer superlattice photodiodes with different passivants

Current–voltage characteristics of long-wave infrared (LWIR) InAs/GaSb strained layer superlattice photodiodes (cut-off wavelength ∼10 μm), passivated with different surface passivants, have been modeled and simulated using ATLAS software from SILVACO. The simulated results are fitted to previous experimental results obtained on unpassivated devices and those passivated by silicon-dioxide (SiO₂), silicon nitride (Si_xN_y) and zinc sulfide (ZnS). Surface parameters in terms of surface recombination velocity, shunt resistance and interface trap density are extracted for different passivants. The performance of silicon-dioxide passivated diode is solely dominated by a shunt leakage path with a shunt resistance value of 0.56 Ω-cm². Extracted electron and hole surface recombination velocities have values of 10⁵ cm/s and 10⁷ cm/s for unpassivated, 10³ cm/s and 10⁵ cm/s for Si_xN_y passivated and 10² cm/s and 10³ cm/s for ZnS passivated devices. Interface trap density follows a similar trend with values of 10¹⁵ cm⁻², 8.5 × 10¹⁴ cm⁻² and 10¹⁰ cm⁻² for unpassivated, Si_xN_y passivated and ZnS passivated devices respectively. The suitability and limitations of the simulation tool are discussed.     

ENO Reconstruction and ENO Interpolation Are Stable

We prove that the ENO reconstruction and ENO interpolation procedures are stable in the sense that the jump of the reconstructed ENO point values at each cell interface has the same sign as the jump of the underlying cell averages across that interface. Moreover, we prove that the size of these jumps after reconstruction relative to the jump of the underlying cell averages is bounded. Similar sign properties and the boundedness of the jumps hold for the ENO interpolation procedure. These estimates, which are shown to hold for ENO reconstruction and interpolation of arbitrary order of accuracy and on nonuniform meshes, indicate a remarkable rigidity of the piecewise polynomial ENO procedure.     

Higher order finite difference schemes for the magnetic induction equations

We describe high order accurate and stable finite difference schemes for the initial-boundary value problem associated with the magnetic induction equations. These equations model the evolution of a magnetic field due to a given velocity field. The finite difference schemes are based on Summation by Parts (SBP) operators for spatial derivatives and a Simultaneous Approximation Term (SAT) technique for imposing boundary conditions. We present various numerical experiments that demonstrate both the stability as well as high order of accuracy of the schemes.