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Identification of intracellular targets of anticancer drug candidates provides key information on their mechanism of action. Exploiting the ability of the anticancer (C^N)-chelated half-sandwich iridium(III) complexes to covalently bind proteins, click chemistry with a bioorthogonal azido probe was used to localize a phenyloxazoline-chelated iridium complex within cells and profile its interactome at the proteome-wide scale. Proteins involved in protein folding and actin cytoskeleton regulation were identified as high affinity targets. Upon iridium complex treatment, HSP90 folding activity was inhibitedin vitroand major cytoskeleton disorganization was observed. We used a wide array of imaging and biochemical methods to validate selected targets and obtain a multiscale overview of the effects of this complex on live human cells. We demonstrate that it behaves as a dual agent, inducing both electrophilic and oxidative stresses in cells that account for its cytotoxicity.

The paper discusses the synchrotron-based microprobe techniques XBIC (X-ray beam induced current), μ-XRF (X-ray fluorescence microscopy) and μ-XAS (X-ray absorption microspectroscopy) and their application for studying electrical activity of defects and precipitation of transition metals in Si materials. Investigations were performed on samples of block-cast multicrystalline Si and on model samples cut from a bonded monocrystalline wafer. To analyze the precipitation sites, Ni, Cu and Fe were introduced intentionally into the samples. The detected precipitates were found to consist of silicides. Evidence for metal precipitates was also found in virtually uncontaminated as-grown block-cast Si. Besides Ni precipitates detected at a recombination active grain boundary, particles containing one or several metals (Cu, Fe, Ti, V) were observed. Unexpectedly, these particles seem to exhibit low only recombination activity. Further studies are necessary to identify their nature. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)