Synthetic directions towards capsular polysaccharide of Streptococcus pneumoniae serotype 18C

An efficient synthetic strategy has been developed for the synthesis of the tri, tetrasaccharide block and pentasaccharide corresponding to the capsular polysaccharide of Streptococcus pneumonia serotype 18C as their 2-aminoethyl glycosides. A one-pot glycosylation-deprotection, sequential glycosylations strategy has been adopted for the construction of the fragments and pentasaccharide derivative, which were then transformed into target compound after a series of functional group transformations. The synthetic method relies on the use of p-methoxybenzyl ether as an in situ-removable protecting group to reduce the number of reaction steps significantly. Here H₂SO₄-silica has been used successfully as a promoter for all glycosylation reaction. In addition, the synthetic target also contained a free amino group at its reducing end, facilitating its conjugation with other molecules for various biological studies and applications.     

Assessment of Reproducibility of Laser Electrospray Mass Spectrometry using Electrospray Deposition of Analyte

A nonresonant, femtosecond (fs) laser is employed to desorb samples of Victoria blue deposited on stainless steel or indium tin oxide (ITO) slides using either electrospray deposition (ESD) or dried droplet deposition. The use of ESD resulted in uniform films of Victoria blue whereas the dried droplet method resulted in the formation of a ring pattern of the dye. Laser electrospray mass spectrometry (LEMS) measurements of the ESD-prepared films on either substrate were similar and revealed lower average relative standard deviations for measurements within-film (20.9%) and between-films (8.7%) in comparison to dried droplet (75.5% and 40.2%, respectively). The mass spectral response for ESD samples on both substrates was linear (R²?>?0.99), enabling quantitative measurements over the selected range of 7.0?×?10^?11 to 2.8?×?10^?9 mol, as opposed to the dried droplet samples where quantitation was not possible (R²?=?0.56). The limit of detection was measured to be 210 fmol.

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Hybrid Curdlan Poly(γ ‐Glutamic Acid) Nanoassembly for Immune Modulation in Macrophage

A nanoformulation composed of curdlan, a linear polysaccharide of 1,3‐β‐linked d ‐glucose units, hydrogen bonded to poly(γ ‐glutamic acid) (PGA), was developed to stimulate macrophage. Curdlan/PGA nanoparticles (C‐NP) are formulated by physically blending curdlan (0.2 mg mL^?1 in 0.4 m NaOH) with PGA (0.8 mg mL^?1). Forster resonance energy transfer (FRET) analysis demonstrates a heterospecies interpolymer complex formed between curdlan and PGA. The ¹H‐NMR spectra display significant peak broadening as well as downfield chemical shifts of the hydroxyl proton resonances of curdlan, indicating potential intermolecular hydrogen bonding interactions. In addition, the cross peaks in ¹H‐¹H 2D‐NOESY suggest intermolecular associations between the OH‐2/OH‐4 hydroxyl groups of curdlan and the carboxylic‐/amide‐groups of PGA via hydrogen bonding. Intracellular uptake of C‐NP occurs over time in human monocyte‐derived macrophage (MDM). Furthermore, C‐NP nanoparticles dose‐dependently increase gene expression for TNF‐α, IL‐6, and IL‐8 at 24 h in MDM. C‐NP nanoparticles also stimulate the release of IL‐lβ, MCP‐1, TNF‐α, IL‐8, IL‐12p70, IL‐17, IL‐18, and IL‐23 from MDM. Overall, this is the first demonstration of a simplistic nanoformulation formed by hydrogen bonding between curdlan and PGA that modulates cytokine gene expression and release of cytokines from MDM.     

Visible Light‐Induced,Metal‐Free Denitrative [3+2] Cycloaddition for Trisubstituted Pyrrole Synthesis

A metal‐free, regioselective synthesis of trisubstituted pyrroles has been developed through a formal [3+2] cycloaddition reaction between 2H‐azirines and nitroalkenes under visible light/photoredox‐catalyzed conditions. The reaction proceeds through 2H‐azaallenyl radical addition on β‐nitrostyrenes in a Michael fashion followed by a base‐mediated denitration reaction. The directive group influence of the nitro group controls the regiochemistry of the reaction.     

Direct Analysis of Proteins from Solutions with High Salt Concentration Using Laser Electrospray Mass Spectrometry

The detection of lysozyme, or a mixture of lysozyme, cytochrome c, and myoglobin, from solutions with varying salt concentrations (0.1 to 250 mM NaCl) is compared using laser electrospray mass spectrometry (LEMS) and electrospray ionization-mass spectrometry (ESI-MS). Protonated protein peaks were observed up to a concentration of 250 mM NaCl in the case of LEMS. In the case of ESI-MS, a protein solution with salt concentration >?0.5 mM resulted in predominantly salt-adducted features, with suppression of the protonated protein ions. The constituents in the mixture of proteins were assignable up to 250 mM NaCl for LEMS and were not assignable above a NaCl concentration of 0.5 mM for ESI. The average sodium adducts (< n >) bound to the 7+ charge state of lysozyme for LEMS measurements from salt concentrations of 2.5, 25, 50, and 100 mM NaCl are 1.71, 5.23, 5.26, and 5.11, respectively. The conventional electrospray measurements for lysozyme solution containing salt concentrations of 0.1, 1, 2, and 5 mM NaCl resulted in < n > of 2.65, 6.44, 7.57, and 8.48, respectively. LEMS displays an approximately two orders of magnitude higher salt tolerance in comparison with conventional ESI-MS. The non-equilibrium partitioning of proteins on the surface of the charged droplets is proposed as the mechanism for the high salt tolerance phenomena observed in the LEMS measurements.

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Cycloaddition of cyclohexa-2,4-dienones, ring-closing metathesis, and photochemical reactions: a common stereoselective approach to duprezianane, polyquinane and sterpurane frameworks

A novel approach to three different types of carbocyclic frameworks belonging to dupreziananes, sterpuranes, and polyquinanes from simple aromatic precursors has been presented. Cycloaddition of appropriately appended cyclohexa-2,4-dienones with acyclic dienes gave bridged bicyclic octanes suitably disposed with olefinic chains, which upon ring-closing metathesis led to functionalized tricyclo[5.2.2.0(1,5)]undecanes related to dupreziananes. Photochemical sigmatropic 1,2- and 1,3-acyl shifts in tricyclo[5.2.2.0(1,5)] undecanes upon triplet and singlet excitation provided stereoselective routes to sterpurane and polyquinane frameworks.     

Structure and dynamics of dodecaborate clusters in water

We have studied using molecular dynamics simulations the interaction of the dodecaborate anion, B(12)H(12)(2-), and its amino, trimethyl, and triethyl derivatives with water molecules. We found peculiar organization of the water molecules in the first solvation shell with the formation of a dihydrogen bond between the hydrogen atoms of the anions and the hydrogen atoms of the water molecules. The simulations also show that the organization of the hydration shell is strongly influenced by the substituents in the anions. These differences are likely to play an important role in understanding the interaction of the anions with biological systems like membranes and proteins in aqueous environments.     

Comprehensive structural studies of 2',3'-difluorinated nucleosides: comparison of theory, solution, and solid state

The conformations of three 2',3'-difluoro uridine nucleosides were studied by X-ray crystallography, NMR spectroscopy, and ab initio calculations in an attempt to define the roles that the two vicinal fluorine atoms play in the puckering preferences of the furanose ring. Two of the compounds examined contained fluorine atoms in either the arabino or xylo dispositions at C2' and C3' of a 2',3'-dideoxyuridine system. The third compound also incorporated fluorine atoms in the xylo configuration on the furanose ring but was substituted with a 6-azauracil base in place of uracil. A battery of NMR experiments in D 2O solution was used to identify conformational preferences primarily from coupling constant and NOE data. Both (1)H and (19)F NMR data were used to ascertain the preferred sugar pucker of the furanose ring through the use of the program PSEUROT. Compound-dependent parameters used in the PSEUROT calculations were newly derived from complete sets of conformations calculated from high-level ab initio methods. The solution and theoretical data were compared to the conformations of each molecule in the solid state. It was shown that both gauche and antiperiplanar effects may be operative to maintain a pseudodiaxial arrangement of the C2' and C3' vicinal fluorine atoms. These data, along with previously reported data by us and others concerning monofluorinated nucleoside conformations, were used to propose a model of how fluorine influences different aspects of nucleoside conformations.     

Semiclassical statistical mechanics of two-dimensional hard-body fluids

The problem of calculating the thermodynamic properties of two-dimensional semiclassical hard-body fluids is studied. Explicit expressions are given for the first-order quantum corrections to the free energy, equation of state, and virial coefficients. The numerical results are calculated for the planar hard dumbbell fluid. Significant features are the increase in quantum corrections with increasing eta and increasing L*=L/sigma(0).