Ein Normalbasissatz für Einheiten algebraischer Zahlkörper

Ohne Zusammenfassung     

Synthesis and Biological Evaluation of 14‐Alkoxymorphinans. Part 19

The 14‐O‐benzylnaltrexones 3 – 6 were prepared from naltrexone ( 2 ) in several steps. The novel compounds were biologically evaluated in radioligand binding and in [³⁵S]GTPγS functional assays in comparison to the reference compound naltrexone. In the binding assay, compounds 3 – 6 exhibited preference for κ opioid receptors, while the parent compound naltrexone shows preference for μ receptors. In the functional assay, μ antagonist potency of compounds 3 – 6 was in the range of naltrexone, while κ antagonist potency was considerably higher for most novel compounds in comparison to naltrexone.     

Development and validation of a robust capillary electrophoresis method for impurity profiling of calcium levofolinate including the (6R,2'S)-diastereomer using statistical experimental design

A chiral capillary electrophoresis assay for the simultaneous determination of the optical purity and of related substances of calcium levofolinate has been developed and validated. Using 2,6-dimethyl-beta-cyclodextrin as chiral selector at a concentration of 20 mg/mL, the method was optimized using a full factorial design with four factors including pH and concentration of the background electrolyte, column temperature and separation voltage. Optimized conditions were a 40 mM sodium tetraborate buffer, pH 9.9, a capillary temperature of 16 degrees C, and an applied voltage of 21 kV. Methotrexate was used as internal standard to compensate for injection errors and fluctuations of the migration times. A multiple linear regression model was also used to test the robustness of the method. Validation was performed with respect to specificity, linearity, range, limit of quantification and detection, precision, and accuracy. The assay allowed the detection and determination of related substances including the diastereomeric (6R,2'S)-impurity of levofolinic acid at the 0.1% level, the identification threshold of impurities for orally administered drugs for human use defined by the International Conference on Harmonization guidelines as well as the European Pharmacopoeia.     

Surface chemistry of ultrathin films of histidine on gold as probed by high-resolution synchrotron photoemission

Procedures for the vacuum deposition of thin histidine films on polycrystalline Au(111) and their characterization with high-resolution synchrotron-radiation-based photoelectron spectroscopy are reported. The chemical form of histidine (anionic vs zwitterionic) and the nature of its interactions with the substrate (strong ionic-covalent vs weak van der Waals bonding) in mono- and multilayer films are analyzed. It is shown that water adsorption on a pre-prepared histidine film at 100 K results in protonation of histidine molecules and partial formation of hydroxyl anions. These chemical effects are carefully differentiated from spectral changes associated with radiation damage of the histidine films.     

"Work-Hardenable" ductile bulk metallic glass

Usually, monolithic bulk metallic glasses undergo inhomogeneous plastic deformation and exhibit poor ductility (< 1%) at room temperature. We present a new class of bulk metallic glass, which exhibits high strength of up to 2265 MPa together with extensive "work hardening" and large ductility of 18%. Significant increase in the flow stress was observed during deformation. The "work-hardening" capability and ductility of this class of metallic glass is attributed to a unique structure correlated with atomic-scale inhomogeneity, leading to an inherent capability of extensive shear band formation, interactions, and multiplication of shear bands.