Isopeptidic Desferrioxamine Analogues: The Role of Hydroxamate Spacing for Chelation of Zr.

[Zr]Zr is a radionuclide of increasing clinical relevance for PET (positron emission tomography). However, an ideal chelator for stable Zr-chelation remains to be discovered. This study describes the solid-phase synthesis of octadentate Zr-chelators based on an isopeptidic (ip) scaffold derived from the natural siderophore desferrioxamine (DFOB).

Iodinated PSMA Ligands as XFI Tracers for Targeted Cell Imaging and Characterization of Nanoparticles.

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes the development of small-molecule tracers for the well-known tumor marker prostate-specific membrane antigen (PSMA).

Medicinal Chemistry of Drugs with -Oxide Functionalities.

Molecules with -oxide functionalities are omnipresent in nature and play an important role in Medicinal Chemistry. They are synthetic or biosynthetic intermediates, prodrugs, drugs, or polymers for applications in drug development and surface engineering. Typically, the -oxide group is critical for biomedical applications of these molecules.

Decoration of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) with N-oxides increases the T relaxivity of Gd-complexes.

High complex stability and longitudinal relaxivity of Gd-based contrast agents are important requirements for magnetic resonance imaging (MRI) because they ensure patient safety and contribute to measurement sensitivity. Charged and zwitterionic Gd-complexes of the well-known chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) provide an excellent basis for the development of safe and sensitive contrast agents. In this report, we describe the synthesis of DOTA-NOx, a DOTA derivative with four N-oxide functionalities via "click" functionalization of the tetraazide DOTAZA.

Low-Fouling and Antibacterial Polymer Brushes via Surface-Initiated Polymerization of a Mixed Zwitterionic and Cationic Monomer.

The use of surface-grafted polymer brushes with combined low-fouling and antibacterial functionality is an attractive strategy to fight biofilm formation. This report describes a new styrene derivative combining a quaternary ammonium group with a sulfobetaine group in one monomer. Surface-initiated polymerization of this monomer on titanium and a polyethylene (PE) base material gave bifunctional polymer brush layers.

Contact-Biocide TiO Surfaces by Surface-Initiated Atom Transfer Radical Polymerization with Chemically Stable Phosphonate Initiators.

Surface-initiated atom transfer radical polymerization (SI-ATRP) is a powerful tool for grafting functional polymers from metal surfaces. It depends on the immobilization of suitable initiators on the surface before radical polymerization. Herein, we report a set of bifunctional initiators bearing a phosphonic acid group for surface binding and a bromoisobutyramide moiety for SI-ATRP.

Synthesis of Modular Desferrioxamine Analogues and Evaluation of Zwitterionic Derivatives for Zirconium Complexation.

The natural siderophore desferrioxamine B (DFOB) has been used for targeted PET imaging with Zr before. However, Zr-DFOB has a limited stability and a number of derivatives have been developed with improved chelation properties for zirconium. We describe the synthesis of pseudopeptidic analogues of DFOB with azido side chains.

Alkali salts of amino acids as alkaline additives for neutralization of acidic corrosion inhibitors.

We present alkali salts of amino acids as functional, non-toxic, non-hazardous, non-volatile, chemically stable, and cheap alkaline additives for common acidic corrosion inhibitors. The resulting mixtures have been evaluated for Co, Ni, and Cu leaching and were analyzed by chip filter assay, potentiodynamic polarization measurements, electrochemical impedance measurements, and gravimetry for corrosion protection of iron and steel in aqueous environment at slightly alkaline pH. Leaching of Co and Ni was found to depend on the corresponding complex stabilities.

Zwitterionic surface modification of polyethylene via atmospheric plasma-induced polymerization of (vinylbenzyl-)sulfobetaine and evaluation of antifouling properties.

Zwitterionic polymer brushes were grafted from bulk polyethylene (PE) by air plasma activation of the PE surface followed by radical polymerization of the zwitterionic styrene derivative (vinylbenzyl)sulfobetaine (VBSB). Successful formation of dense poly-(VBSB)-brush layers was confirmed by goniometry, IR spectroscopy, XPS and ToF-SIMS analysis. The resulting zwitterionic layers are about 50-100 nm thick and cause extremely low contact angles of 10° (water) on the material.

Natural Product-Derived Phosphonic Acids as Corrosion Inhibitors for Iron and Steel.

Organic acids, typically derived from an oil-based value chain, are frequently used as corrosion inhibitors in industrial metal working fluids. The criteria for selection of these corrosion inhibitors have changed in the last decades, and are today not only performance-driven, but influenced by ecological considerations, toxicity and regulatory standards. We present scalable semisynthetic approaches to organic corrosion inhibitors based on phosphonic acids from renewable resources.

X-ray Fluorescence Uptake Measurement of Functionalized Gold Nanoparticles in Tumor Cell Microsamples.

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells.

X-ray-Based Techniques to Study the Nano-Bio Interface.

X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction.

Regulation of dual leucine zipper kinase activity through its interaction with calcineurin.

Hyperglycemia enhancing the intracellular levels of reactive oxygen species (ROS) contributes to dysfunction and progressive loss of beta cells and thereby to diabetes mellitus. The oxidation sensitive calcium/calmodulin dependent phosphatase calcineurin promotes pancreatic beta cell function and survival whereas the dual leucine zipper kinase (DLK) induces apoptosis. Therefore, it was studied whether calcineurin interferes with DLK action.

Contact-active antibacterial polyethylene foils via atmospheric air plasma induced polymerisation of quaternary ammonium salts.

Polyethylene (PE) foils were modified with potent contact-active antibacterial quaternary ammonium salts (QAS) by an atmospheric air plasma activation step, followed by graft-polymerisation of vinylbenzyltrimethylammonium chloride (VBTAC) monomers. The presented approach uses a cost efficient air plasma activation and subsequent radical polymerisation in highly concentrated aqueous monomer solutions to generate efficient antibacterial materials. The obtained contact-active poly-VBTAC modified PE foils feature a homogeneous and 300 nm thick polymer layer with a high charge density of approximately 10 N/cm.

Nonradioactive Cell Assay for the Evaluation of Modular Prostate-Specific Membrane Antigen Targeting Ligands via Inductively Coupled Plasma Mass Spectrometry.

The development of novel prostate-specific membrane antigen (PSMA)-targeted radioactive theranostic agents is currently limited to facilities capable of working with high-energy radioisotopes. Even preselection of lead structures in vitro relies mostly on radioactive assays with PSMA(+) LNCaP and PSMA(-) PC-3 cells. Assays utilizing radioisotopes are time consuming, costly, and limit discovery to a small group of scientists with special facilities.

Exploring Rigid and Flexible Core Trivalent Sialosides for Influenza Virus Inhibition.

Herein, the chemical synthesis and binding analysis of functionalizable rigid and flexible core trivalent sialosides bearing oligoethylene glycol (OEG) spacers interacting with spike proteins of influenza A virus (IAV) X31 is described. Although the flexible Tris-based trivalent sialosides achieved micromolar binding constants, a trivalent binder based on a rigid adamantane core dominated flexible tripodal compounds with micromolar binding and hemagglutination inhibition constants. Simulation studies indicated increased conformational penalties for long OEG spacers.

Investigation of Antifouling Properties of Surfaces Featuring Zwitterionic α-Aminophosphonic Acid Moieties.

Zwitterionic thin films containing α-amino phosphonic acid moieties were successfully introduced on silicon surfaces and their antifouling properties were investigated. Initially, the substrates were modified with a hybrid polymer, composed of poly(methylsilsesquioxane) (PMSSQ) and poly(4-vinyl benzaldehyde) (PStCHO). Next, a Kabachnik-Fields post-polymerization modification (sur-KF-PMR) of the functionalized aldehyde surfaces was conducted with different amines and dialkyl phosphonates.

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles.

A common approach to generate tailored materials and nanoparticles (NPs) is the formation of molecular monolayers by chemisorption of bifunctional anchor molecules. This approach depends critically on the choice of a suitable anchor group. Recently, bifunctional catecholates, inspired by mussel-adhesive proteins (MAPs) and bacterial siderophores, have received considerable interest as anchor groups for biomedically relevant metal surfaces and nanoparticles.

Epithelial transport of immunogenic and toxic gliadin peptides in vitro.

Scope: Celiac disease is an autoimmune disorder caused by failure of oral tolerance against gluten in genetically predisposed individuals. The epithelial translocation of gluten-derived gliadin peptides is an important pathogenetic step; the underlying mechanisms, however, are poorly understood. Thus, we investigated the degradation and epithelial translocation of two different gliadin peptides, the toxic P31-43 and the immunogenic P56-68.

Variants of the prins cyclization for the synthesis of terpenoid spiroethers and oxabicyclo[3.3.1]nonane derivatives.

Terpenoid spiroethers are abundant natural flavors with significant impact, particularly in the food industry. We present in this article the synthesis of new derivatives of the well-known flavors theaspirane and vitispirane using a variant of the Prins cyclization starting from α,β-unsaturated or heterocyclic ketones. When aromatic ketones were used as the starting materials for Lewis acid-mediated cyclizations, an alternative pathway involving a domino sequence of Prins cyclization, followed by an intramolecular Friedel-Crafts alkylation, gave benzoannelated oxabicyclo[3.

High-affinity carbohydrate binding by trimeric benzoboroxoles measured on carbohydrate arrays.

Carbohydrates are involved in a wide range of biological processes of pharmaceutical relevance. The selective recognition of carbohydrates is therefore of great interest in biology and medicine. In this study we present the synthesis of fluorescent multimeric benzoboroxoles and the analysis of multivalent binding processes to immobilized carbohydrate arrays by fluorescence spectroscopy.

Enantioselective high performance liquid chromatography and supercritical fluid chromatography separation of spirocyclic terpenoid flavor compounds.

Chiral spirocyclic terpenoids are abundant natural flavors with significant impact particularly on the food industry. Chromatographic methods for analytical and preparative separation of these compounds are therefore of high interest to natural product chemists in academia and industry. Gas chromatography on chiral stationary phases is currently the standard method for the separation of volatile terpenoids, limiting the scale to analytical quantities.

Synthesis of 1,4,7,10-tetra-azacyclododecan-1,4,7,10-tetra-azidoethylacetic acid (DOTAZA) and related "clickable" DOTA derivatives.

Herein, we report the synthesis of two enantiomeric DOTAZA esters and a related DOT3AZA ester. These compounds are tunable analogues of the well-known chelator DOTA and can be easily functionalized through click chemistry of the side-chain azide groups. Like DOTA, DOTAZA forms complexes with various di- and trivalent metals, as demonstrated in the synthesis and structural analysis of CuDOTAZA and the preparation of GdDOTAZA.

Biomimetic PEG-catecholates for stabile antifouling coatings on metal surfaces: applications on TiO2 and stainless steel.

Trimeric catecholates have been designed for the stable immobilization of effector molecules on metal surfaces. The design of these catecholates followed a biomimetic approach and was inspired by natural multivalent metal binders, such as mussel adhesion proteins (MAPs) and siderophores. Three catecholates have been conjugated to central scaffolds based on adamantyl or trisalkylmethyl core structures.

Impact of S-adenosylmethionine decarboxylase 1 on pulmonary vascular remodeling.

Background: Pulmonary hypertension (PH) is a life-threatening disease characterized by vascular remodeling and increased pulmonary vascular resistance. Chronic alveolar hypoxia in animals is often used to decipher pathways being regulated in PH. Here, we aimed to investigate whether chronic hypoxia-induced PH in mice can be reversed by reoxygenation and whether possible regression can be used to identify pathways activated during the reversal and development of PH by genome-wide screening.