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Bacterial adhesion, biofilm formation and host cell invasion of the ESKAPE pathogen Pseudomonas aeruginosa require the tetravalent lectins LecA and LecB, which are therefore drug targets to fight these infections. Recently, we have reported highly potent divalent galactosides as specific LecA inhibitors. However, they suffered from very low solubility and an intrinsic chemical instability due to two acylhydrazone motifs, which precluded further biological evaluation. Here, we isosterically substituted the acylhydrazones and systematically varied linker identity and length between the two galactosides necessary for LecA binding. The optimized divalent LecA ligands showed improved stability and were up to 1000-fold more soluble. Importantly, these properties now enabled their biological characterization. The lead compound L2 potently inhibited LecA binding to lung epithelial cells, restored wound closure in a scratch assay and reduced the invasiveness of P. aeruginosa into host cells.  相似文献   
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Ammonolysis of (CO)5M · PCl3 (M = Cr, Mo, W) results in the formation of the complexes (CO)5M · P(NH2)3, stable at ambient temperature. IR data indicate that P(NH2)3, which is unstable in the free state under the same conditions, transfers about the same electron density to the metal atom as P(NMe2)3. Other spectral data (NMR, mass spectra) are discussed.  相似文献   
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The understanding of the physico-chemical processes leading to the formation and weathering of ore deposits plays an increasingly important role in mineral exploration. Synchrotron, neutron, and nuclear radiation are contributing to this endeavour in many ways, including (i) support the modelling of ore transport and deposition, by providing molecular-level understanding of solvent–solute interaction and thermodynamic properties for the important metal complexes in brines, vapours, and supercritical fluids over the range of conditions relevant for the formation of ore deposits (i.e., temperature 25–600 °C; pressure 1–109 Pa; and fluid compositions varying from hypersaline (e.g., >50 wt% NaCl) to volatile-rich (e.g., CO2, CH4, and H2S)); (ii) track the fluids that travelled through rocks and predict their ore-forming potential by analysing hydrothermal minerals and remnants of those fluids trapped in these minerals as ‘fluid inclusions’; (iii) characterize the biochemical controls on metal mobility in soils to predict the geochemical footprint of a buried mineral deposit.X-ray fluorescence (XRF), particle-induced X-ray emission (PIXE), and X-ray absorption spectroscopy (XAS) are the most common techniques used in support of mineral exploration. Analytical challenges are related to (i) the complexity of heterogeneous natural samples, which often contain only low concentrations of the elements of interest; (ii) beam sensitivity, especially for redox-sensitive elements in aqueous fluids or biological samples; (iii) extreme sample environments, e.g., in-situ study of fluids at high pressure and temperature. Thus, critical improvements need to be made on a number of fronts to: (i) develop more efficient detectors, able to map large areas in heterogeneous samples (e.g., 106–108 pixels per map), and also to collect a maximum number of photons to limit sample exposure and beam damage; (ii) integrate techniques (e.g., XRF, XAS, and X-ray diffraction (XRD)) on a single beamline, and promote synergy between neutron-, synchrotron-, and nuclear microprobe-based methods; (iii) advance the theory (e.g., quantitative XANES interpretation; X-ray extended range technique (XERT) measurements) to gain maximum information from the hard-won datasets.  相似文献   
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Zusammenfassung Nach der Schönigerschen Methode ist die gleichzeitige Bestimmung des Schwefel- und Halogengehaltes bisher nur dann möglich gewesen, wenn die Substanz frei von Stickstoff war. Es wird beschrieben, wie durch Kombination verschiedener maßanalytischer Verfahren Halogen (Cl, Br, J) und Schwefel in allen organischen Verbindungen nach der Schönigerschen Methode mit einer Fehlergrenze von ± 0,3% bestimmt werden können.
Summary According to theSchöniger method, the concurrent determination of sulfur and halogen has hitherto been possible only if the sample is free of nitrogen. It is shown how a combination of various titrimetric procedures makes it possible to determine halogen (Cl, Br, I) and sulfur in all organic compounds by theSchöniger method with a limit of error of ± 0.3%.

Résumé La détermination simultanée du soufre et des halogènes par la méthode deSchöniger n'est applicable que lorsque la substance ne contient pas d'azote. L'auteur décrit comment il est possible de déterminer simultanément les halogènes (Cl, Br, I), et le soufre dans toutes combinaisons organiques avec une limite d'erreur de ± 3%par l'association de techniques titrimétriques diverses.


Vorgetragen auf der Chemiedozenten-Tagung Rostock 23. bis 25. Mai 1957.  相似文献   
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