Unusual stereoselectivity of methionine-γ-lyase from Citrobacterfreundii toward diastereomeric (S)-methionine S-oxide

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Tuning Ruthenium Carbene Complexes for Selective P−H Activation through Metal-Ligand Cooperation

The use of iminophosphoryl-tethered ruthenium carbene complexes to activate secondary phosphine P−H bonds is reported. Complexes of type [(p-cymene)-RuC(SO₂Ph)(PPh₂NR)] (with R = SiMe₃ or 4-C₆H₄−NO₂) were found to exhibit different reactivities depending on the electronics of the applied phosphine and the substituent at the iminophosphoryl moiety. Hence, the electron-rich silyl-substituted complex undergoes cyclometallation or shift of the imine moiety after cooperative activation of the P−H bond across the M=C linkage, depending on the electronics of the applied phosphine. Deuteration experiments and computational studies proved that cyclometallation is initiated by the activation process at the M=C bond and triggered by the high electron density at the metal in the phosphido intermediates. Consistently, replacement of the trimethylsilyl (TMS) group by the electron-withdrawing 4-nitrophenyl substituent allowed the selective cooperative P−H activation to form stable activation products.     

Understanding the Stability and Lifetime of Emulsions

This paper aims to review the various degradation pathays of emulsions. Aging of emulsions may proceed through three distinct microscopic mechanisms: diffusion or permeation, dewetting, and coalescence, each one being associated with a very characteristic growth scenario. We show within this context how double emulsions are a unique tool to complete the basic understanding of emulsion metastability.     

Efficient Entropy-Driven Inhibition of Dipeptidyl Peptidase III by Hydroxyethylene Transition-State Peptidomimetics

Dipeptidyl peptidase III (DPP3) is a ubiquitously expressed Zn-dependent protease, which plays an important role in regulating endogenous peptide hormones, such as enkephalins or angiotensins. In previous biophysical studies, it could be shown that substrate binding is driven by a large entropic contribution due to the release of water molecules from the closing binding cleft. Here, the design, synthesis and biophysical characterization of peptidomimetic inhibitors is reported, using for the first time an hydroxyethylene transition-state mimetic for a metalloprotease. Efficient routes for the synthesis of both stereoisomers of the pseudopeptide core were developed, which allowed the synthesis of peptidomimetic inhibitors mimicking the VVYPW-motif of tynorphin. The best inhibitors inhibit DPP3 in the low μM range. Biophysical characterization by means of ITC measurement and X-ray crystallography confirm the unusual entropy-driven mode of binding. Stability assays demonstrated the desired stability of these inhibitors, which efficiently inhibited DPP3 in mouse brain homogenate.     

Studies on the metabolism and detectability of the emerging drug of abuse diphenyl‐2‐pyrrolidinemethanol (D2PM) in rat urine using GC‐MS and LC‐HR‐MS/MS

In the last years, the number of new psychoactive substances, so‐called ‘legal highs’, has enormously increased. They are sold via online shops often with inaccurate and false information about the content. The aim of this work was to study the metabolism and the detectability of the drug of abuse diphenyl‐2‐pyrrolidinemethanol (D2PM) in rat urine using gas chromatography‐mass spectrometry and liquid chromatography‐high resolution‐tandem mass spectrometry. Five phase I and two phase II metabolites were identified suggesting hydroxylation at the pyrrolidine and diphenyl part as the main metabolic steps. Assuming similar kinetics, an intake of D2PM should be detectable in human urine mainly via its metabolites. Copyright © 2013 John Wiley & Sons, Ltd.