High yield synthesis of 4H‐1,4‐benzothiazine‐1,1‐dioxide derivatives

4H‐1,4‐Benzothiazine‐1,1‐dioxide derivatives were synthesized through a sequence of almost quantitative reactions. The commercial starting material 2‐(methylsulfanyl)aniline was Boc‐protected, N‐acylated and oxidized at the sulfur atom to obtain a sulfonyl derivative. An anionic transposition of the acyl group followed by asimultaneous deprotection‐cyclization gave the title products in excellent yields. All products and intermediates were fully characterized.     

Synthesis and an evaluation of the bioactivity of the C-glycoside of pseudopterosin A methyl ether

The Suzuki-Miyaura cross-coupling protocol was applied to the synthesis of 1a, the C-glycoside analogue of PsA methyl ether. This marks the first construction of a C-glycoside for this class of marine natural products, thereby offering an opportunity to compare its bioactivity to the natural substances. Its activity profile resembled that of PsA (1) and PsA O-methyl ether (1b) when assayed for its anti-inflammatory activity and its ability to inhibit phagocytosis. We conclude that the intact structure is present when a pseudopterosin expresses its anti-inflammatory and phagocytosis inhibitory properties and that they are, therefore, not likely to be prodrugs. Results show that 1a is an effective binding agent toward the A2A and A3 adenosine receptors, displaying IC50 values of 20 and 10 microM, respectively.     

Chip‐based electrochromatography coupled to ESI‐MS detection

In this study, we present the coupling of chip‐based electrochromatography to MS using a glass chip with a monolithically integrated nanoelectrospray emitter. As separation column, an acrylate‐based porous polymer monolith is implemented into the glass chip by photopolymerization. For the establishment and development of this method, we used a test mixture detectable with both fluorescence and ESI‐MS. After successful evaluation of the approach with the test solutes, it was applied exemplarily for drug analysis such as high‐speed separations of benzodiazepines in pharmaceuticals.     

Nucleophilic Aromatic Substitution on Pentafluorophenyl‐Substituted Dipyrranes and Tetrapyrroles as a Route to Multifunctionalized Chromophores for Potential Application in Photodynamic Therapy

The application of porphyrinoids in biomedical fields, such as photodynamic therapy (PDT), requires the introduction of functional groups to tune their solubility for the biological environment and to allow a coupling to other active moieties or carrier systems. A valuable motif in this regard is the pentafluorophenyl (PFP) substituent, which can easily undergo a regiospecific nucleophilic replacement (S_NAr) of its para‐fluorine atom by a number of nucleophiles. Here, it is shown that, instead of amino‐substitution on the final porphyrinoid or BODIPY (boron dipyrromethene), the precursor 5‐(PFP)‐dipyrrane can be modified with amines (or alcohols). These dipyrranes were transformed into amino‐substituted BODIPYs. Condensation of these dipyrranes with aldehydes gave access to trans‐A₂B₂‐porphyrins and trans‐A₂B‐corroles. By using pentafluorobenzaldehyde, it was possible to introduce another para‐fluorine atom, which enabled the synthesis of multifunctionalized tetrapyrroles. Furthermore, alkoxy‐ and amino‐substituted dipyrranes were applied to the synthesis of A₃B₃‐hexaphyrins. The polar porphyrins that were prepared by using this method exhibited in vitro PDT activity against several tumor cell lines.     

An interlaboratory comparison on whole water samples

The European Water Framework Directive 2000/60/EC requires monitoring of organic priority pollutants in so-called whole water samples, i.e. in aqueous non-filtered samples that contain natural colloidal and suspended particulate matter. Colloids and suspended particles in the liquid phase constitute a challenge for sample homogeneity and stability. Within the joint research project ENV08 “Traceable measurements for monitoring critical pollutants under the European Water Framework Directive 2000/60/EC”, whole water test materials were developed by spiking defined amounts of aqueous slurries of ultra-finely milled contaminated soil or sediment and aqueous solutions of humic acid into a natural mineral water matrix. This paper presents the results of an European-wide interlaboratory comparison (ILC) using this type of test materials. Target analytes were tributyltin, polybrominated diphenyl ethers and polycyclic aromatic hydrocarbons in the ng/L concentration range. Results of the ILC indicate that the produced materials are sufficiently homogeneous and stable to serve as samples for, e.g. proficiency testing or method validation. To our knowledge, this is the first time that ready-to-use water materials with a defined amount of suspended particulate and colloidal matter have been applied as test samples in an interlaboratory exercise. These samples meet the requirements of the European Water Framework Directive. Previous proficiency testing schemes mainly employed filtered water samples fortified with a spike of the target analyte in a water-miscible organic solvent.     

Reversible Electrocatalytic Activity of Carbon‐Supported PtxNi1−x in Hydrogen Reactions

Hydrogen oxidation and evolution reactions (HOR and HER) are studied on Pt_xNi_1?x/C materials synthesized by the bromide anion exchange method. Physicochemical characterization shows that this surfactant‐free method enables the preparation of well‐dispersed and effective catalysts for the processes involved in the anode of H₂/O₂ fuel cells (HOR) and the cathode of water electrolyzers (HER). The Pt‐based materials are modified with different Ni contents to decrease the amount of costly precious metal in the electrode materials. These modified Pt‐based materials are found to be electroactive for both reactions without additional overpotential. Kinetic parameters such as the Tafel slope, exchange (j₀) and kinetic current densities, and the rate‐determining steps of the reaction mechanisms are determined for each Pt–Ni catalyst and compared to those obtained at the Pt/C surface in alkaline medium. The high j₀ values that are obtained indicate a probable contribution of the surface structure of the catalysts due to their roughness and the presence of oxygenated Ni species even at low potentials.     

Four Classes of Structurally Unusual Peptides from Two Marine-Derived Fungi: Structures and Bioactivities

The structures and biological properties of peptides produced by two genera of marine-derived fungi, an atypical Acremonium sp., and a Metarrhizium sp., were explored. The Acremonium strain was isolated from a marine sponge and has previously been shown by our group to produce peptides from the efrapeptin and RHM families. The isolation and structural elucidation of the new linear pentadecapeptides efrapeptins Eα (1) and H (2) and N-methylated octapeptides RHM3 (3) and RHM4 (4) were carried out through a combination of 1D and 2D NMR techniques and tandem MS. Additional known efrapeptins E, F, and G and the known syctalidamides A and B were also isolated. The absolute configurations of 1-4 are proposed to be the same as the original compound families. The marine sponge-derived Metarrhizium sp. was shown to produce destruxin cyclic depsipeptides including A, B, B2, desmethyl B, E chlorohydrin, and E2 chlorohydrin. Efrapeptins Eα (1), F, and G each displayed IC₅₀s of 1.3 nM against H125 cells, and destruxin E2 chlorohydrin displayed an IC₅₀ of 160 nM against HCT-116 cells. An initial therapeutic assessment suggested a continuous (168 h) exposure of at least 2 ng/mL, or a daily (24 h) exposure of at least 300 ng/mL for H125 cells treated with efrapeptin G, and a continuous (168 h) exposure of at least 190 ng/mL for HCT-116 cells treated with destruxin E2 chlorohydrin, will cause 90% tumor cell death in vitro.     

Micro-BLMs on highly ordered porous silicon substrates: rupture process and lateral mobility

In a recent paper, we hypothesized that the continuous increase in membrane conductance observed for nano-BLMs is the result of an independent rupturing of single membranes or membrane patches covering the pores of the porous material. To prove this hypothesis, we prepared micro-BLMs on porous silicon substrates with a pore size of 7 mum. The upper surface of the silicon substrate was coated with a gold layer, followed by the chemisorption of 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol (DPPTE) and subsequent addition of a droplet of 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) dissolved in n-decane. The lipid membranes were fluorescently labeled and investigated by means of fluorescence microscopy and impedance spectroscopy. Impedance spectroscopy revealed the formation of pore-suspending bilayers with high membrane resistance. Increases in membrane capacitance and membrane conductance were observed. This increase in membrane conductance could be unambiguously related to the individual rupturing of membranes suspending the pores of the porous material as visualized by means of fluorescence microscopy. Moreover, by fluorescence recovery after photobleaching experiments, we investigated the lateral mobility of the lipids within the micro-BLMs leading to a mean effective diffusion coefficient of Deff = (14 +/- 1) microm2/s.     

Effect of surface parameters on the performance of IgG-arrayed hydrogel chips: a comprehensive study

In this article, the assay performance of 3D polyurethane (PU) hydrogel surfaces, used either plain or modified with cross linkers and additives in a direct immunoassay for IgG, is correlated with chip surface parameters such as water content and expansion, mechanical stability, hydrophilicity, thickness, and surface topography. Commercial chip surfaces ARChip Epoxy, Nexterion slide H and HydroGel are used as references. A strong correlation between assay sensitivity and physical surface parameters was found only for various hydrogels of the same chemical composition, in which cases assay sensitivity increases with decreasing hydrogel concentration as well as decreasing roughness, water content, and expansion. However, as is the case with all hydrogels tested, more hydrophobic layers with low water content are more highly reproducible from one measurement to another.