Frontispiece: Cationic Tetrylene-Iron(0) Complexes: Access Points for Cooperative,Reversible Bond Activation and Open-Shell Iron(−I) Ferrato-Tetrylenes

The open-shell cationic stannylene-iron(0) complex 4 ( 4 =[^PhiPDippSn⋅Fe⋅IPr]⁺; ^PhiPDipp={[Ph₂PCH₂Si(ⁱPr)₂](Dipp)N}; Dipp=2,6-ⁱPr₂C₆H₃; IPr=[(Dipp)NC(H)]₂C:) cooperatively and reversibly cleaves dihydrogen at the Sn−Fe interface under mild conditions (1.5 bar, 298 K), in forming bridging hydrido-complex 6 . The One-electron oreduction of the related Ge^II−Fe⁰ complex 3 leads to oxidative addition of one C−P linkage of the ^PhiPDipp ligand in an intermediary Fe^−I complex, leading to Fe^I phosphide species 7 . One-electron reduction reaction of 4 gives access to the iron(−I) ferrato-stannylene, 8 , giving evidence for the transient formation of such a species in the reduction of 3 . The covalently bound tin(II)-iron(−I) compound 8 has been characterised through EPR spectroscopy, SQUID magnetometry, and supporting computational analysis, which strongly indicate a high localization of electron spin density at Fe^−I in this unique d⁹-iron complex.     

Metabolism of methylstenbolone studied with human liver microsomes and the uPA+/+‐SCID chimeric mouse model

Anti‐doping laboratories need to be aware of evolutions on the steroid market and elucidate steroid metabolism to identify markers of misuse. Owing to ethical considerations, in vivo and in vitro models are preferred to human excretion for nonpharmaceutical grade substances. In this study the chimeric mouse model and human liver microsomes (HLM) were used to elucidate the phase I metabolism of a new steroid product containing, according to the label, methylstenbolone. Analysis revealed the presence of both methylstenbolone and methasterone, a structurally closely related steroid. Via HPLC fraction collection, methylstenbolone was isolated and studied with both models. Using HLM, 10 mono‐hydroxylated derivatives (U1–U10) and a still unidentified derivative of methylstenbolone (U13) were detected. In chimeric mouse urine only di‐hydroxylated metabolites (U11–U12) were identified. Although closely related, neither methasterone nor its metabolites were detected after administration of isolated methylstenbolone. Administration of the steroid product resulted mainly in the detection of methasterone metabolites, which were similar to those already described in the literature. Methylstenbolone metabolites previously described were not detected. A GC‐MS/MS multiple reaction monitoring method was developed to detect methylstenbolone misuse. In one out of three samples, previously tested positive for methasterone, methylstenbolone and U13 were additionally detected, indicating the applicability of the method. Copyright © 2014 John Wiley & Sons, Ltd.     

Epitope Mapping of Monoclonal Antibodies using Synthetic Oligosaccharides Uncovers Novel Aspects of Immune Recognition of the Psl Exopolysaccharide of Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic Gram‐negative bacterium that can cause life‐threatening infections in critically ill and cystic fibrosis patients. The Psl exopolysaccharide of P. aeruginosa offers an attractive serotype‐independent antigen for the development of immunotherapies. Here, the first chemical synthesis of a panel of oligosaccharides derived from the exopolysaccharide of P. aeruginosa by a synthetic strategy that efficiently deals with the stereoselective installation of several β‐mannosides and the formation of a mannoside that is extended by saccharide moieties at C‐1, C‐2, and C‐3 in a crowded 1,2,3‐cis configuration is described. The approach was employed to prepare tetra‐, penta‐, and hexa‐ and decasaccharide part structures. The compounds were employed to define the epitope requirements of several functionally active monoclonal antibodies (mAbs) that can bind three distinct epitopes of Psl (class I, II, and III). The class II mAb reacted potently with each oligosaccharide indicating its epitope resides within the tetrasaccharide and does not require the branched mannoside of Psl. The class III antibody did not bind the tetra‐ or pentasaccharide; however, it did react potently with the hexasaccharide and weakly with the decasaccharide, suggesting a terminal glucoside is required for optimal binding. Unexpectedly, the class I mAb did not bind any of the oligosaccharides indicating that Psl contains a yet to be elucidated sub‐stoichiometric isoform. This study demonstrates that functional activity of a mAb does not only depend on the avidity of binding but also on the location of an epitope within a bacterial polysaccharide. The results also provide a strong impetus to analyze further the structure of Psl to identify the class I epitope, that is expected to provide an attractive target for the development of a synthetic vaccine for P. aeruginosa.     

Raman micro‐spectroscopy for quantitative thickness measurement of nanometer thin polymer films

The sensitivity of far‐field Raman micro‐spectroscopy was investigated to determine quantitatively the actual thickness of organic thin films. It is shown that the thickness of organic films can be quantitatively determined down to 3 nm with an error margin of 20% and down to 1.5 nm with an error margin of 100%. Raman imaging of thin‐film surfaces with a far‐field optical microscope establishes the distribution of a polymer with a lateral resolution of ~400 nm and the homogeneity of the film. Raman images are presented for spin‐coated thin films of polysulfone (PSU) with average thicknesses between 3 and 50 nm. In films with an average thickness of 43 nm, the variation in thickness was around 5% for PSU. In films with an average thickness of 3 nm for PSU, the detected thickness variation was 100%. Raman imaging was performed in minutes for a surface area of 900 µm². The results illustrate the ability of far‐field Raman microscopy as a sensitive method to quantitatively determine the thickness of thin films down to the nanometer range. Copyright © 2015 John Wiley & Sons, Ltd.