Small-molecule screening identifies the selanazal drug ebselen as a potent inhibitor of DMT1-mediated iron uptake

HEK293T cells overexpressing divalent metal transporter-1 (DMT1) were established to screen for small-molecule inhibitors of iron uptake. Using a fluorescence-based assay, we tested 2000 known bioactive compounds to find 3 small molecules that potently block ferrous iron uptake. One of the inhibitors, ebselen, is a seleno compound used in clinical trials as a protective agent against ischemic stroke. Ebselen inhibited Fe(II) uptake (IC(50) of approximately 0.22 microM), but did not influence Fe(III) transport or DMT1-mediated manganese uptake. An unrelated antioxidant, pyrrolidine dithiobarbamate (PDTC), also inhibited DMT1 activity (IC(50) of approximately 1.54 microM). Both ebselen and PDTC increased cellular levels of reduced glutathione. These observations indicate that Fe(II) transport by DMT1 can be modulated by cellular redox status and suggest that ebselen may act therapeutically to limit iron-catalyzed damage due to transport inhibition.     

Full hemispherical photoelectron diffraction and Fermi surface mapping

The routine measurement of full hemispherical photoemission intensity maps gives us the possibility for the combined investigation of structural and electronic phenomena at surfaces. As an example the growth of ultrathin films of Co on Cu(111) is studied as a function of film thickness. While X-ray photoelectron diffraction (XPD) shows the early appearance of stacking faults as a precursor of the hcp structure, Fermi surface maps reveal the very fast evolution of the Co Fermi surface that can be compared to measurements on a clean Co(0001) crystal. For the system O/Rh(111), XPD brings up important structural clues, relating changes in surface reactivity to small amounts of subsurface oxygen, which forces adjacent oxygen atoms to occupy new and more reactive adsorption sites. In the course of this last study we observed for the first time the weak backscattering signals in the angular pattern of adsorbate emission. These cone-like features are extremely sensitive to the adsorbate–substrate bond length.     

Surface composition of Ni-10at%A1(111) in thermodynamic equilibrium

Ion-scattering spectroscopy using 1000 eV He ions was applied to determine the equilibrium concentration at the (111) surface of Ni-10at%Al. Special care was taken to eliminate the falsification of the results by sulfur segregation as well as by the effects of sputtering. A technique for rapid determination of the surface concentrations is presented. It was found that the surface has to be annealed at 800°C or higher to reach the equilibrium with 25 at% Al. The surface composition remains unchanged if the temperature is subsequently varied between 700°C and 1000°C.     

Automated screening platform with isochronal-parallel analysis and conditioning for rapid method development of chiral separations

An automated chiral separation-screening platform was developed, allowing separation analysis on one column while another column is simultaneously equilibrated with a different mobile phase (MP). The platform can be set up from usual HPLC components at moderate cost and it considerably speeds up the screening process, allowing numerous chromatographic conditions to be tested within a short period of time and leading to a significant gain in time and productivity in preparative separations.