Synthesis of unnatural cyclitols via a combined enzymatic-palladium catalysis approach

The Suzuki-Miyaura cross-coupling reaction of a hydroxylated vinyl bromide obtained by a chemoenzymatic approach with a diverse range of potassium organotrifluoroborates has been accomplished catalyzed by Pd(PPh(3))(4) in satisfactory yields. A variety of functional groups are tolerated in the nucleophilic partner. (C) 2008 Elsevier B.V. All rights reserved.

Direct Zincation of Functionalized Aromatics and Heterocycles by Using a Magnesium Base in the Presence of ZnCl(2)

A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF by using (TMP)(2)Mg center dot 2LiCl (TMP = 2,2,6,6-tetramethylpiperamidyl) in the presence of ZnCl(2). The possible pathways of this metalation procedure as well as possible reactive intermediates are discussed. This experimental protocol expands the tolerance of functional groups and allows an efficient zincation of sensitive heterocycles such as quinoxaline or pyrazine. The zincated arenes and heteroarenes react with various electrophiles providing the expected products in 60-95 % yield.

Characterization of interactions between polyphenolic compounds and human serum proteins by capillary electrophoresis

The interaction of ten natural polyphenolic compounds (chlorogenic acid, apigenin, catechin, epicatechin, flavanone, flavone, quercetin, rutin, vicenin-2 and vitexin) with human serum albumin and mixtures of human serum albumin and alpha(1)-acid glycoprotein under near physiological conditions is studied by capillary electrophoresis-frontal analysis. Furthermore, the binding of these polyphenolic compounds to total plasmatic proteins is evaluated using ultrafiltration and capillary electrophoresis. In spite of the relatively small differences in the chemical structures of the compounds studied, large differences were observed in their binding behaviours to plasmatic proteins. The hydrophobicity, the presence/absence of some functional groups, steric hindrance and spatial arrangement seem to be key factors in the affinity of natural polyphenols towards plasmatic proteins.

Hydrothermal Stability of Modified Silica Membranes for Gas Separation

A new class of hybrid molecular sieve silica (MSS) membranes is developed and tested against standard and organic templated membranes. The hybrid membrane is synthesized by the standard sol-gel process, integrating a template (methyltriethoxysilane - MTES) and a C6 surfactant (triethylhexylammonium bromide) into the silica film matrix. After hydro treatment under a relative humidity of 96% for 50h, the hybrid membrane shows no changes in its gas separation capabilities or energy of mobility. The structural characteristics and integrity of the hybrid membrane are retained due to a high concentration of organophilic functional groups and alkoxides observed using 29 Si NMR. In contrast, the structural integrity of the membranes prepared with non-templated films deteriorated during the hydro treatment due to a large percentage of silanol groups (Si-OH) which react with water. The hybrid membranes underwent a decrease in the H2/CO2 selectivity of only 1% whereas for the non-templated membrane a 21% decrease was observed. The transport mechanism of the hybrid membranes is activated as permeation increased with temperature. The activation energy for the permeation of H2 is positive while negative for CO2. The H2 permeation obtained was 3x 10 -8 mol.m -2 .s -1 .Pa -1 and permselectivities for H2/CO2 and H2/N2 varied between 1-7 and 31-34, respectively.

A modified discrete random pore model allowing for different initial surface reactivity

We investigate here a modification of the discrete random pore model [Bhatia SK, Vartak BJ, Carbon 1996;34:1383], by including an additional rate constant which takes into account the different reactivity of the initial pore surface having attached functional groups and hydrogens, relative to the subsequently exposed surface. It is observed that the relative initial reactivity has a significant effect on the conversion and structural evolution, underscoring the importance of initial surface chemistry. The model is tested against experimental data on chemically controlled char oxidation and steam gasification at various temperatures. It is seen that the variations of the reaction rate and surface area with conversion are better represented by the present approach than earlier random pore models. The results clearly indicate the improvement of model predictions in the low conversion region, where the effect of the initially attached functional groups and hydrogens is more significant, particularly for char oxidation. It is also seen that, for the data examined, the initial surface chemistry is less important for steam gasification as compared to the oxidation reaction. Further development of the approach must also incorporate the dynamics of surface complexation, which is not considered here.

Modification of MCM-41 by surface silylation with trimethylchlorosilane and adsorption study

Siliceous MCM-41 samples were modified by silylation using trimethylchlorosilane (TMCS). The surface coverage of functional groups was studied systematically in this work. The role of surface silanol groups during modification was evaluated using techniques of FTIR and Si-29 CP/MAS NMR. Adsorption of water and benzene on samples of various hydrophobicities was measured and compared. It was found that the maximum degree of surface attachments of trimethylsilyl (TMS) groups was about 85%, corresponding to the density of TMS groups of 1.9 per nm(2). The degree of silylation is found to linearly increase with increasing pre-outgassing temperature prior to silylation. A few types of silanol groups exist on MCM-41 surfaces, among which both free and geminal ones are responsible for active silylation. Results of water adsorption show that aluminosilicate MCM-41 materials are more or less hydrophilic, giving a type IV isotherm, similar to that of nitrogen adsorption, whereas siliceous MCM-41 are hydrophobic, exhibiting a type V adsorption isotherm. The fully silylated Si-MCM-41 samples are more hydrophobic giving a type III adsorption isotherm. Benzene adsorption on all MCM-41 samples shows type IV isotherms regardless of the surface chemistry. Capillary condensation occurs at a higher relative pressure for the silylated MCM-41 than that for the unsilylated sample, though the pore diameter was found reduced markedly by silylation. This is thought attributed to the diffusion constriction posed by the attached TMS groups. The results show that the surface chemistry plays an important role in water adsorption, whereas benzene adsorption is predominantly determined by the pore geometry of MCM-41.

Solid-phase extraction method with high-performance liquid chromatography and electrochemical detection for the quantitative analysis of oxycodone in human plasma

A sensitive and reproducible solid-phase extraction (SPE) method for the quantification of oxycodone in human plasma was developed. Varian Certify SPE cartridges containing both C-8 and benzoic acid functional groups were the most suitable for the extraction of oxycodone and codeine (internal standard), with consistently high (greater than or equal to 80%) and reproducible recoveries. The elution mobile phase consisted of 1.2 ml of butyl chloride-isopropanol (80:20, v/v) containing 2% ammonia. The quantification limit for oxycodone was 5.3 pmol on-column. Within-day and inter-day coefficients of variation were 1.2% and 6.8% respectively for 284 nM oxycodone and 9.5% and 6.2% respectively for 28.4 nM oxycodone using 0.5-ml plasma aliquots. (C) 1998 Elsevier Science BN. All rights reserved.

NMR structure of C-terminally tagged gramicidin channels

A biotin group was covalently attached to the C terminus of gramicidin A (gA) through a linker arm comprising a glycine residue with either one (gAXB) or two caproyl groups (gAXXB). High-resolution two-dimensional NMR spectroscopy was used to determine the structure of these modified gA analogues and [Lys(16)]gramicidin A (gA-Lys) in sodium dodecyl-d(25) sulphate micelles. Gated gA ion channels based on linking a receptor group to these gA analogues have been used recently as a component in a sensing device. The conformations of the gA backbones and amino acid side chains of lysinated gA and biotinylated gA in detergent micelles were found to be almost identical to that of native gA, i.e. that of an N-terminal to N-terminal (head to head) dimer formed by two right-handed, single-stranded beta(6.3) helices. The biotin tail of the gAXB and gAXXB and the lysine extremity of gA-Lys appeared to lie outside the micelle. Thus it appears that the covalent attachment of functional groups to the C terminus of gA does not disrupt the peptide's helical configuration. Further, single channel measurements of all three gA analogues showed that functioning ion channels were preserved within a membrane environment. (C) 1999 Elsevier Science B.V. All rights reserved.

Carbon structure and porosity of carbonaceous adsorbents in relation to their adsorption properties

A number of carbonaceous adsorbents were prepared by carbonisation at 600 degrees C following acidic oxidation under various conditions. Effects of the chemical nature of the precursor, such as the ratio of aromatic to aliphatic carbons and oxygen content, on the chemical and structural characteristics of the resultant chars were investigated using C-13 NMR and Raman spectroscopy, respectively. The C-13 NMR spectral parameters of the coal samples show that as the severity of oxidation conditions increased, the ratio of aromatic to aliphatic carbons increased. Furthermore, it was also found that the amount of disorganised carbon affects both the pore structure and the adsorption properties of carbonaceous adsorbents. It is demonstrated that higher amount of the disorganised carbon indicates smaller micropore size. (C) 1999 Elsevier Science Ltd. All rights reserved.

A proteome analysis of conditioned media from human neonatal fibroblasts used in the maintenance of human embryonic stem cells

The pathways involved in the maintenance of human embryonic stem (hES) cells remain largely unknown, although some signaling pathways have been identified in mouse embryonic stem (mES) cells. Fibroblast feeder layers are used to maintain the undifferentiated growth of hES cells and an examination of the conditioned media (CM) of human neonatal fibroblasts (HNFs) could provide insights into the maintenance of hES cells. The neonatal foreskin fibroblast line (HNF02) used in this study was shown to have a normal 2n = 46, XY chromosomal complement and to support the undifferentiated growth of the Embryonic Stem Cell International Pte. Ltd.-hES3 cell line. The CM of HNF02 was examined using two-dimensional liquid chromatography-tandem mass spectrometry (2-D LCMS) and two-dimensional electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization-time of flight tandem mass spectrometry (2-DE/MALDI). A total of 102 proteins were identified, 19 by 2-DE/MALDI, 53 by 2-D LCMS and 30 by both techniques. These proteins were classified into 15 functional groups. Proteins identified in the extracellular matrix and differentiation and growth factor functional categories were considered most likely to be involved in the maintenance of hES cell growth, differentiation and pluripotency as these groups contained proteins involved in a variety of events including cell adhesion, cell proliferation and inhibition of cell proliferation, Writ signaling and inhibition of bone morphogenetic proteins.

2-Methoxy-6-methyl-3-nitro-4-(2-nitroprop-1-enyl)phenyl acetate

In the title compound, C13H14N2O7, steric crowding around the aromatic ring results in significant out-of-plane twisting of the nitro, methoxy, acetoxy and 2-nitropropenyl functional groups. These distortions are explained by comparison with less congested substituted benzene analogues.

Crystal structure at 1.1 angstrom resolution of alpha-conotoxin PnIB: Comparison with alpha-conotoxins PnIA and GI

Conotoxins are small, cysteine-rich peptides isolated from the venom of Conus spp. of predatory marine snails, which selectively target specific receptors and ion channels critical to the functioning of the neuromuscular system. alpha-Conotoxins PnIA and PnIB are both 16-residue peptides (differing in sequence at only two positions) isolated from the molluscivorous snail Conus pennaceus. In contrast to the muscle-selective alpha-conotoxin GI from Conus geographus, PnIA and PnIB block the neuronal nicotinic acetylcholine receptor (nAChR). Here, we describe the crystal structure of PnIB, solved at a resolution of 1.1 Angstrom and phased using the Shake-and-Bake direct methods program. PnIB crystals are orthorhombic and belong to the space group P2(1)2(1)2(1) with the following unit cell dimensions: a = 14.6 Angstrom, b = 26.1 Angstrom, and c = 29.2 Angstrom. The final refined structure of alpha-conotoxin PnIB includes all 16 residues plus 23 solvent molecules and has an overall R-factor of 14.7% (R-free of 15.9%). The crystal structures of the alpha-conotoxins PnIB and PnIA are solved from different crystal forms, with different solvent contents. Comparison of the structures reveals them to be very similar, showing that the unique backbone and disulfide architecture is not strongly influenced by crystal lattice constraints or solvent interactions. This finding supports the notion that this structural scaffold is a rigid support for the presentation of important functional groups. The structures of PnIB and PnIA differ in their shape and surface charge distribution from that of GI.

Hydrophobicity of Templated Silica Xerogels for Molecular Sieving Applications

Silica xerogels were prepared by a sol-gel process catalyzed by acid with tetraethylorthosilicate, and using an organic covalent ligand template (methyltriethoxysilane) or a noncovalent template C6 surfactant (triethylhexylammonium bromide). The influence of hydrotreatment on the structure of templated xerogels is examined in terms of surface area, micropore volume, average pore size, and pore size distribution, and compared against a blank xerogel (nontemplated). The role of surface functional groups was evaluated using Si-29 nuclear magnetic resonance. The structural integrity of the xerogel was maintained to a large extent in samples that had a high contribution of Q(4) species (siloxane groups). Xerogel matrix densification occurred when there was a large concentration of Q(3) and Q(2) species (silanol groups), which also were responsible for increased hydrophilicity. The templated xerogels resulted in up to a 25% concentration of methyl functional groups (T-3 and T-2 species), leading to hydrophobic xerogels. The best results in terms of structural integrity and hydrophobicity were obtained with templated xerogels prepared with the C6 surfactant. The results in this study suggest that surfactant-enhanced condensation reactions lead to structures with a high contribution of Q(4) groups, which are not susceptible to water attack, but are strong enough to oppose matrix densification during rehydration.

A classification of subantarctic Heard Island vegetation

The vascular and bryophyte floras of subantarctic Heard Island were classified using cluster analysis into six vegetation communities: Open Cushion Carpet, Mossy Feldmark, Wet Mixed Herbfield, Coastal Biotic Vegetation, Saltspray Vegetation, and Closed Cushion Carpet. Multidimensional scaling indicated that the vegetation communities were not well delineated but were continua. Discriminant analysis and a classification tree identified altitude, wind, peat depth, bryophyte cover and extent of bare ground, and particle size as discriminating variables. The combination of small area, glaciation, and harsh climate has resulted in reduced vegetation variety in comparison to those subantarctic islands north of the Antarctic Polar Front Zone. Some of the functional groups and vegetation communities found on warmer subantarctic islands are not present on Heard Island, notably ferns and sedges and fernbrakes and extensive mires, respectively.

Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics

Alcoholism is a major health problem in Western countries, yet relatively little is known about the mechanisms by which chronic alcohol abuse causes the pathologic changes associated with the disease. It is likely that chronic alcoholism affects a number of signaling cascades and transcription factors, which in turn result in distinct gene expression patterns. These patterns are difficult to detect by traditional experiments measuring a few mRNAs at a time, but are well suited to microarray analyses. We used cDNA microarrays to analyze expression of approximately 10 000 genes in the frontal and motor cortices of three groups of chronic alcoholic and matched control cases. A functional hierarchy was devised for classification of brain genes and the resulting groups were compared based on differential expression. Comparison of gene expression patterns in these brain regions revealed a selective reprogramming of gene expression in distinct functional groups. The most pronounced differences were found in myelin-related genes and genes involved in protein trafficking. Significant changes in the expression of known alcohol-responsive genes, and genes involved in calcium, cAMP, and thyroid signaling pathways were also identified. These results suggest that multiple pathways may be important for neuropathology and altered neuronal function observed in alcoholism.