Design of molecular scaffolds based on unusual geometries for magnetic modulation of spin-diverse complexes with selective redox response

A weakly coupled heterometallic [CuFe] complex has been prepared in which the metal centers are coordinated to a new electroactive ligand. The spin-diverse system delivers distinct ground states upon application of selective redox potentials. Ligand oxidation fosters radical generation, and the initial ground state associated with a weakly coupled [CuFe] core switches to a ground state associated with the [Fe-radical] coupling; the Cu(II) ion remains uncoupled. A third state is obtained upon reduction of the cupric center and in absence of the radical. The possibilities and limitations of these systems are discussed.     

Sulfur-alkylation-initiated CpRu thiyl radicals

The formation of thiyl radicals from [Cp^∗Ru^III{κ³SSS′-tpdt}] (1A) and [Cp^∗Ru^III{κ³SSN-apdt}] (1B) {Cp^∗ = η⁵-C₅Me₅; tpdt = S(CH₂CH₂S⁻)₂; apdt = HN(CH₂CH₂S⁻)₂} has been initiated by thiolate alkylation or oxidation with iodine. Subsequent electron transfer processes yielded disulfide-bridged dinuclear complexes. The mechanistic pathways of these processes will be discussed.     

Microcalorimetric research on recombinant <Emphasis Type="Italic">Escherichia coli</Emphasis> with high production of polyhydroxyalkanoates (PHAs)

The thermogenic curves of metabolism of the four strains of Escherichia coli pUC19cab/JM109, pUC19cab/XL-IBlue, JM109 and XL-IBlue were determined using the LKB-2277 BioActivity Monitor and the ampoule method at 37°C. The pUC19cab/JM109 and pUC19cab/XL-IBlue are recombinant E. coli strains bearing the same foreign plasmid pUC19cab, which confers the ability to produce polyhydroxyalkanoates (PHAs). The yield of PHAs of pUC19cab/XL-IBlue was higher than that of pUC19cab/JM109. XL-IBlue and JM109 were the host bacteria. The heat flow of these strains was XL-Blue≈JM109>pUC19cab/JM109>pUC19cab/XL-IBlue. These results indicate an obvious interrelation between the PHAs production and the heat flow rate of E. coli strains.     

Composite sequence proteomic analysis of protein biomarkers of Campylobacter coli, C. lari and C. concisus for bacterial identification

Protein biomarkers observed in the matrix-assisted laser desorption/ionization time-of-flight mass spectra (MALDI-TOF-MS) of cell lysates of three strains of Campylobacter coli, two strains of C. lari and one strain of C. concisus have been identified by 'bottom-up' proteomic techniques. The significant findings are as follows. First, the protein biomarkers identified were: PhnA-related protein, 4-oxalocrotonate tautomerase (DmpI)-related protein, NifU-like protein, cytochrome c, DNA-binding protein HU, 10 kDa chaperonin, thioredoxin, as well as several conserved hypothetical and ribosomal proteins. Second, variations in the biomarker ion m/z in MALDI-TOF-MS spectra across species and strains are the result of variations in the amino acid sequence of the protein due to non-synonymous mutations of the biomarker gene. Third, the most common post-translational modifications (PTMs) were the removal of the N-terminal methionine and N-terminal signal peptides. However, in the case of the NifU protein (an iron-sulfur cluster transport protein), post-translational cleavage occurred from the C-terminus. Fourth, only the genomes of the C. coli strain RM2228 and C. lari strain RM2100 have been sequenced; thus, proteomic identification of the proteins of the other strains in this study relied upon sequence homology to the genomic sequence of these strains as well as the genomes of sequences of other Campylobacter strains. In some cases, the determination of the full amino acid sequence of a protein biomarker from a genomically non-sequenced strain was accomplished by combining non-overlapping partial sequences from proteomic identifications of genomically-sequenced strains that were of the same species (or of a different species) to that of the non-sequenced strain. The accuracy of this composite sequence was confirmed by both MS and MS/MS. It was necessary, in some cases, to perform de novo sequencing on 'gaps' in the composite sequence that were not homologous to any genomically-sequenced strain. In order to validate the composite sequence approach, composite sequences were further confirmed by subsequent DNA sequencing of the biomarker gene. Thus, using the composite sequence approach, it was possible to determine the full amino acid sequence of an unknown protein from a genomically non-sequenced bacterial strain without the necessity of either sequencing the biomarker gene or performing full de novo MS/MS sequencing. The sequence obtained could then be used as a strain-specific biomarker for analysis by 'top-down' proteomics techniques.     

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-kappaB and hypoxia-inducible factor-1alpha

Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-kappaB and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-kappaB and HIF-1alpha as well as reducing ROS generation in allergic airway disease.     

Chemistry of thienopyridines. XXXVIII. Diels-Alder reactions of thienopyridine sulfones. Part 2

Thieno[3,2-b]pyridine 1,1-dioxide ( 2 ) undergoes Diels-Alder condensation with the dienophiles cyclopentadiene, anthracene, and naphthacene in a manner analogous to its isomer thieno[2,3-b]pyridine 1,1-dioxide ( 1 ). Compound 2 dimerizes in refluxing xylene with the loss of sulfur dioxide plus either the loss or transfer of hydrogen to give a small yield (ca. 2%) of pyrido[2′,3′:4,5]thieno[3,2-f]quinoline 7,7-dioxide ( 7 ) and its 5,6-dihydro derivative 12 . Formation of 7 and 12 are compared and contrasted with products reported from dimerization of 1 and of benzo[b]thiophene 1,1-dioxide and its derivatives.     

Mild and Selective Catalytic Hydrogenation of the C=C Bond in α,β‐Unsaturated Carbonyl Compounds Using Supported Palladium Nanoparticles

Chemoselective reduction of the C=C bond in a variety of α,β‐unsaturated carbonyl compounds using supported palladium nanoparticles is reported. Three different heterogeneous catalysts were compared using 1 atm of H₂: 1) nano‐Pd on a metal–organic framework (MOF: Pd⁰‐MIL‐101‐NH₂(Cr)), 2) nano‐Pd on a siliceous mesocellular foam (MCF: Pd⁰‐AmP‐MCF), and 3) commercially available palladium on carbon (Pd/C). Initial studies showed that the Pd@MOF and Pd@MCF nanocatalysts were superior in activity and selectivity compared to commercial Pd/C. Both Pd⁰‐MIL‐101‐NH₂(Cr) and Pd⁰‐AmP‐MCF were capable of delivering the desired products in very short reaction times (10–90 min) with low loadings of Pd (0.5–1 mol %). Additionally, the two catalytic systems exhibited high recyclability and very low levels of metal leaching.     

An explanation of dispersion states of single-walled carbon nanotubes in solvents and aqueous surfactant solutions using solubility parameters

Dispersions of single-walled carbon nanotubes in various solvents and aqueous surfactant emulsions were investigated to correlate the degree of dispersion state with Hansen solubility parameters (deltat2=deltad2+deltap2+deltah2). It was found that the nanotubes were dispersed or suspended very well in the solvents with certain dispersive component (deltad) values. They were precipitated in the solvents with high polar component (deltap) values or hydrogen-bonding component (deltah) values. The solvents in the dispersed group occupied a certain region in a 3-dimensional space of three components. The surfactants with a lipophilic group equal to and longer than decyl, containing 9 methylene groups and 1 methyl group, contributed to the dispersion of nanotubes in water. The surfactants in the dispersed group had a lower limit in the dispersive component (deltad) of the Hansen parameter.     

Aqueous phase behavior and dispersed nanoparticles of diglycerol monooleate/glycerol dioleate mixtures

The first part of this study concerns the aqueous phase behavior of mixtures of diglycerol monooleate (DGMO) and glycerol dioleate (GDO) examined by X-ray diffraction (XRD). The ternary phase diagram displays a multitude of liquid crystalline phases (polymorphism). With increasing GDO content the following phase sequence was observed: lamellar (L(alpha)); two reversed bicontinuous cubic phases (Q(230) and Q(224)); reversed hexagonal (H(II)); the reversed micellar (L(2)) phase. The second part deals with the preparation and characterization of aqueous dispersions of the reversed hexagonal phase in the presence of the nonionic triblock copolymer Pluronic F127. Submicrometer-sized monocrystalline H(II) phase particles were obtained, as evidenced by cryo-transmission electron microscopy (cryo-TEM), laser diffraction, and XRD, by use of a simple and reproducible preparation method including a heat-treatment step. Moreover, the particle size distributions of the H(II) phase nanoparticle dispersions were narrow as determined by laser diffraction measurements. Using XRD, we show that the polymeric stabilizer is depleted from the core of the hexagonal particles and preferentially located at the surface. It is concluded that the preferential distribution of stabilizing agents at particle surfaces is a prerequisite for the formation of structurally well-defined and kinetically stable H(II) phase particles (Hexosome).     

Microchip separations of protein biotoxins using an integrated hand-held device

We report the development of a hand-held instrument capable of performing two simultaneous microchip separations (gel and zone electrophoresis), and demonstrate this instrument for the detection of protein biotoxins. Two orthogonal analysis methods are chosen over a single method in order to improve the probability of positive identification of the biotoxin in an unknown mixture. Separations are performed on a single fused-silica wafer containing two separation channels. The chip is housed in a microfluidic manifold that utilizes o-ring sealed fittings to enable facile and reproducible fluidic connection to the chip. Sample is introduced by syringe injection into a septum-sealed port on the device exterior that connects to a sample loop etched onto the chip. Detection of low nanomolar concentrations of fluorescamine-labeled proteins is achieved using a miniaturized laser-induced fluorescence detection module employing two diode lasers, one per separation channel. Independently controlled miniature high-voltage power supplies enable fully programmable electrokinetic sample injection and analysis. As a demonstration of the portability of this instrument, we evaluated its performance in a laboratory field test at the Defence Science and Technology Laboratory with a series of biotoxin variants. The two separation methods cleanly distinguish between members of a biotoxin test set. Analysis of naturally occurring variants of ricin and two closely related staphylococcal enterotoxins indicates the two methods can be used to readily identify ricin in its different forms and can discriminate between two enterotoxin isoforms.