Toward the Rational Design of Galactosylated Glycoclusters That Target Pseudomonas aeruginosa Lectin A (LecA): Influence of Linker Arms That Lead to Low‐Nanomolar Multivalent Ligands

Anti‐infectious strategies against pathogen infections can be achieved through antiadhesive strategies by using multivalent ligands of bacterial virulence factors. LecA and LecB are lectins of Pseudomonas aeruginosa implicated in biofilm formation. A series of 27 LecA‐targeting glycoclusters have been synthesized. Nine aromatic galactose aglycons were investigated with three different linker arms that connect the central mannopyranoside core. A low‐nanomolar (K_d=19 nm , microarray) ligand with a tyrosine‐based linker arm could be identified in a structure–activity relationship study. Molecular modeling of the glycoclusters bound to the lectin tetramer was also used to rationalize the binding properties observed.     

Effects of the physicochemical properties of titanium dioxide nanoparticles, commonly used as sun protection agents, on microvascular endothelial cells

Until now, the potential effects of titanium dioxide (TiO₂) nanoparticles on endothelial cells are not well understood, despite their already wide usage. Therefore, the present work characterizes six TiO₂ nanoparticle samples in the size range of 19 × 17 to 87 × 13 nm, which are commonly present in sun protection agents with respect to their physicochemical properties (size, shape, ζ-potential, agglomeration, sedimentation, surface coating, and surface area), their interactions with serum proteins and biological impact on human microvascular endothelial cells (relative cellular dehydrogenase activity, adenosine triphosphate content, and monocyte chemoattractant protein-1 release). We observed no association of nanoparticle morphology with the agglomeration and sedimentation behavior and no variations of the ζ-potential (?14 to ?19 mV) in dependence on the surface coating. In general, the impact on endothelial cells was low and only detectable at concentrations of 100 μg/ml. Particles containing a rutile core and having rod-like shape had a stronger effect on cell metabolism than those with anatase core and elliptical shape (relative cellular dehydrogenase activity after 72 h: 60 vs. 90 %). Besides the morphology, the nanoparticle shell constitution was found to influence the metabolic activity of the cells. Upon cellular uptake, the nanoparticles were localized perinuclearly. Considering that in the in vivo situation endothelial cells would come in contact with considerably lower nanoparticle amounts than the lowest-observable adverse effects level (100 μg/ml), TiO₂ nanoparticles can be considered as rather harmless to humans under the investigated conditions.     

Taylor Expansions of Distributions

Classical Taylor expansions of holomorphic functions in the complex plane are extended to distributions in Rⁿand in domains     

Metal‐Supported Aluminosilicate Ultrathin Films as a Versatile Tool for Studying the Surface Chemistry of Zeolites

The application of a variety of “surface‐science” techniques to elucidate surface structures and mechanisms of chemical reactions at zeolite surfaces has long been considered as almost impossible because of the poor electrical and thermal conductivity of those materials. Here, we show that the growth of a thin aluminosilicate film on a metal single crystal under controlled conditions results in adequate and well‐defined model systems for zeolite surfaces. In principle, silicate films that contain metals other than Al (e.g. Ti, Fe, etc) may be prepared in a similar way. We believe that this approach opens up a new playground for experimental and theoretical modeling of zeolites, aimed at a fundamental understanding of structure–reactivity relationships in such materials.     

An Experimental Study of a Flux Modulated Solid State Metathesis Reaction

A solid state metathesis (SSM) reaction was investigated with respect to the formation of rare‐earth carbodiimides, the role of the co‐produced salt (LiCl), and the eutectic flux medium (LiCl/KCl). A SSM reaction is characterized by an exothermic reaction in which a salt (often LiCl) is coproduced. When the salt melts, it can serve as a useful medium for the crystallization of a desired product. An improved crystal growth can be observed by using an eutectic flux. However, the composition of an eutectic LiCl/KCl flux is altered when LiCl is produced during the reaction. The thermal effects concerning the endothermic melting of the flux and the exothermic ingnition of the SSM reaction may compensate each other, which is not necessarily a drawback for the reaction to proceed.     

Characterization of two major urinary metabolites of the PPARδ-agonist GW1516 and implementation of the drug in routine doping controls

Since January 2009, the list of prohibited substances and methods of doping as established by the World Anti-Doping Agency includes new therapeutics such as the peroxisome-proliferator-activated receptor (PPAR)-delta agonist GW1516, which is categorized as a gene doping substance. GW1516 has completed phase II and IV clinical trials regarding dyslipidemia and the regulation of the lipoprotein transport in metabolic syndrome conditions; however, its potential to also improve athletic performance due to the upregulation of genes associated with oxidative metabolism and a modified substrate preference that shifted from carbohydrate to lipid consumption has led to a ban of this compound in elite sport. In a recent report, two presumably mono-oxygenated and bisoxygenated urinary metabolites of GW1516 were presented, which could serve as target analytes for doping control purposes after full characterization. Hence, in the present study, phase I metabolism was simulated by in vitro assays employing human liver microsomal fractions yielding the same oxygenation products, followed by chemical synthesis of the assumed structures of the two abundant metabolic reaction products. These allowed the identification and characterization of mono-oxygenated and bisoxygenated metabolites (sulfoxide and sulfone, respectively) as supported by high-resolution/high-accuracy mass spectrometry with higher-energy collision-induced dissociation, tandem mass spectrometry, and nuclear magnetic resonance spectroscopy. Since urine samples have been the preferred matrix for doping control purposes, a method to detect the new target GW1516 in sports drug testing samples was developed in accordance to conventional screening procedures based on enzymatic hydrolysis and liquid–liquid extraction followed by liquid chromatography, electrospray ionization, and tandem mass spectrometry. Validation was performed for specificity, limit of detection (0.1 ng/ml), recovery (72%), intraday and interday precisions (7.7–15.1%), and ion suppression/enhancement effects (<10%).