Catalyst Activation,Deactivation, and Degradation in Palladium‐Mediated Negishi Cross‐Coupling Reactions

Pd‐mediated Negishi cross‐coupling reactions were studied by a combination of kinetic measurements, electrospray‐ionization (ESI) mass spectrometry, ³¹P NMR and UV/Vis spectroscopy. The kinetic measurements point to a rate‐determining oxidative addition. Surprisingly, this step seems to involve not only the Pd catalyst and the aryl halide substrate, but also the organozinc reagent. In this context, the ESI‐mass spectrometric observation of heterobimetallic Pd–Zn complexes [L₂PdZnR]⁺ (L=S‐PHOS, R=Bu, Ph, Bn) is particularly revealing. The inferred presence of these and related neutral complexes with a direct Pd–Zn interaction in solution explains how the organozinc reagent can modulate the reactivity of the Pd catalyst. Previous theoretical calculations by González‐Pérez et al. (Organometallics­ 2012 , 31, 2053) suggest that the complexation by the organozinc reagent lowers the activity of the Pd catalyst. Presumably, a similar effect also causes the rate decrease observed upon addition of ZnBr₂. In contrast, added LiBr apparently counteracts the formation of Pd–Zn complexes and restores the high activity of the Pd catalyst. At longer reaction times, deactivation processes due to degradation of the S‐PHOS ligand and aggregation of the Pd catalyst come into play, thus further contributing to the appreciable complexity of the title reaction.     

Development of a Multimatrix UHPLC-MS/MS Method for the Determination of Paracetamol and Its Metabolites in Animal Tissues

Paracetamol/acetaminophen (APAP) is one of the most popular pharmacologically active substances used as an analgesic and antipyretic agent. The metabolism of this drug occurs in the liver and leads to the formation of two main metabolites—glucuronic acid and sulfate derivate. Despite the wide use of paracetamol in veterinary medicine, a handful of analytical methods were published for the determination of paracetamol residues in animal tissues. In this paper, a multimatrix method has been developed for the determination of paracetamol and two metabolites—paracetamol sulfate (PS) and p-Acetamidophenyl β-D-glucuronide (PG). A validation procedure was conducted to verify method reliability and fit purpose as a tool for analyzing acetaminophen and metabolites in muscle, liver, lung, and kidney samples from different species of animals. Established validation parameters were in agreement with acceptable criteria laid by the European legislation. The initial significant matrix effect was successfully reduced by implementing an internal standard—4-Acetamidophenyl β-D-glucuronide-d3 (PG-d3, IS). The usefulness of the developed method was verified by analyzing samples from an experiment in which paracetamol was administrated to geese.     

The Role of Formamidine Groups in Dextran Based Nonviral Vectors for Gene Delivery on Their Physicochemical and Biological Characteristics

Dextran‐formamidine esters (dextran‐N‐[(dimethylamino)methylene]‐β‐alanine ester) with different degrees of substitution (0.45–0.92) are synthesized in an one‐pot reaction. Dextran (Mw 60 000 g mol^?1) is allowed to react with unprotected beta‐alanine and iminium chloride and investigated regarding the potential as gene delivery system for the transfer of plasmid DNA. With degrees of substitution ≥ 0.63 improved DNA binding with formation of enzymatically stable complexes of about 130–160 nm with negative surface charges are obtained. These physicochemical characteristics correlated with increasing transfection rates in CHO‐K1 cells determined by a luciferase reporter gene assay in dependency of the number of formamidine residues, N/P ratios and amount of DNA. The role of the number of formamidine groups is also highlighted by in vitro cyto‐ and hemotoxicity tests under the chosen conditions. These results indicate that dextran‐formamidine esters are a very promising material for the safe and efficient gene delivery.     

Thin liquid droplet on top of a rotating non-isothermal liquid layer

Wafers are usually coated by using spin-coating, where centrifugal forces are used to spread a droplet on the rotating wafer. This flow is unstable to the fingering instability, where several segments of the wetting front spread faster than the average, resulting in several fingers. The liquid flows via the existing fingers while the area in between does not get coated. A precise experimental investigation is problematic, as the droplet has to be placed quite exactly in the center of the rotation. Replacing the wafer by a second liquid should lead to a parabolic-shaped free interface and the droplet should center itself due to gravity. Here, we derive a model for the free interfaces of a thin droplet on top of a rotating liquid by taking gravity, centrifugal forces, friction, (thermo-)capillary and line forces into account. Additionally, this setup is the simplest example of multiple coating, where several free interfaces and contact lines influence each other. (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Bounding the Clique‐Width of H‐Free Chordal Graphs

A graph is H‐free if it has no induced subgraph isomorphic to H. Brandstädt, Engelfriet, Le, and Lozin proved that the class of chordal graphs with independence number at most 3 has unbounded clique‐width. Brandstädt, Le, and Mosca erroneously claimed that the gem and co‐gem are the only two 1‐vertex P₄‐extensions H for which the class of H‐free chordal graphs has bounded clique‐width. In fact we prove that bull‐free chordal and co‐chair‐free chordal graphs have clique‐width at most 3 and 4, respectively. In particular, we find four new classes of H‐free chordal graphs of bounded clique‐width. Our main result, obtained by combining new and known results, provides a classification of all but two stubborn cases, that is, with two potential exceptions we determine all graphs H for which the class of H‐free chordal graphs has bounded clique‐width. We illustrate the usefulness of this classification for classifying other types of graph classes by proving that the class of ‐free graphs has bounded clique‐width via a reduction to K₄‐free chordal graphs. Finally, we give a complete classification of the (un)boundedness of clique‐width of H‐free weakly chordal graphs.     

Elastischer Halbraum mit unendlich langein Biegeträger

Übersicht Das Zusammenwirken von Biegeträger und Halbraum wird mit Hilfe der Fouriertransformation untersucht. Eine sin- oder cos-förmige Streifenlast ruft sowohl am Träger wie auch auf der Oberfläche des elastischen Halbraumes eine in Trägerlängsrichtung sinoder cos-förmige Verformung hervor. Wenn durch Auswertung der Einflußfläche für die Durchsenkung der Halbraumoberfläche der Zusammenhang zwischen Last- und Verformungsamplitude gewonnen ist, kann das Zusammenwirken von Träger und Halbraum für sinoder cos-förmige Streifenlast und mit der Pouriertransformation auch für andere Lasten angegeben werden.

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Elastic beam supported on an elastic half space

Summary This work ist directed toward the Fourier transform solution for the problem of the interaction between an elastic beam and an supporting elastic half space. A spatial harmonic load is applied along the longitudinal axis of an elastic beam. This results in a harmonic beam deflection, which in turn introduces a harmonic load in the elastic half space. In this manner it ist possible to relate the resulting half space deflections to the applied loads, and to resolve the applied load to beam and half space proportions. Comparison is made between this solution and the conventional solution of a beam resting on an elastic foundation.

     

Disciformycins A and B: 12‐Membered Macrolide Glycoside Antibiotics from the Myxobacterium Pyxidicoccus fallax Active against Multiresistant Staphylococci

Two macrolide glycosides with a unique scaffold were isolated from cultures of the myxobacterium Pyxidicoccus fallax. Their structures, including absolute configurations, were elucidated by a combination of NMR, MS, degradation, and molecular modeling techniques. Analysis of the proposed biosynthetic gene cluster led to insights into the biosynthesis of the polyketide and confirmed the structure assignment. The more active compound, disciformycin B, potently inhibits methicillin‐ and vancomycin‐resistant Staphylococcus aureus.