Highly enantioselective organocatalytic direct aldol reaction in an aqueous medium

We have demonstrated that small organic molecules 1 and 2 catalyzed the direct aldol reaction of both acyclic and cyclic ketones with different aldehydes in an excess of water/brine. Excellent enantioselectivities up to >99% and diastereoselectivities up to 99% with very good yields were obtained by using much lower catalyst loadings (0.5 mol %).     

Interaction of the antimicrobial peptide dicynthaurin with membrane phospholipids at the air-liquid interface

This paper reports the first study on the interaction of the antimicrobial peptide dicynthaurin with 1,2-dipalmitoyl-glycerophosphatidyl-glycerol investigated in monolayers at the air-liquid interface. The influence of the peptide on the two-dimensional phase behavior of the negatively charged lipid was elucidated by means of pressure-area isotherm measurements, fluorescence microscopy, and grazing incidence X-ray diffraction measurements. The pure peptide forms a stable monolayer at the air-liquid interface up to 30 mN/m as shown for both the monomeric and the dimeric cynthaurins. The peptide lipid interaction was monitored in isotherm measurements showing a strong adsorption of the peptide and stabilization at the interface promoted by the lipid monolayer. The X-ray diffraction measurements in agreement with fluorescence microscopy studies showed that the peptide destabilizes the condensed chain lattice, leading to a complete fluidization of the condensed lipid phase on physiological buffer. The adsorption of the peptide to the negatively charged lipid monolayer and the fluidization of the condensed chain lattice suggest a direct link to the peptides' ability to expand the bacterial membrane that would be relevant for the in vivo mode of action.     

Synthesis of TiO2 nanoparticles on the Au(111) surface

The growth of titanium oxide nanoparticles on reconstructed Au(111) was investigated by scanning tunneling microscopy and x-ray photoelectron spectroscopy. Ti was deposited by physical-vapor deposition at 300 K. Regular arrays of titanium nanoparticles form by preferential nucleation of Ti at the elbow sites of the herringbone reconstruction. The titanium oxide nanoclusters were synthesized by subsequent exposure to O(2) at 300 K. Two-and three-dimensional titanium oxide nanocrystallites form during annealing in the temperature range from 600 to 900 K. At the same time, the Au(111) surface assumes a serrated 110-oriented step-edge morphology suggesting step-edge pinning by titanium oxide nanoparticles. The oxidation state of the titanium oxide nanoparticles varies with annealing temperature. Specifically, annealing to 900 K results in the formation of stoichiometric TiO(2) nanocrystals as judged by the Ti(2p) binding energies measured in the x-ray photoelectron data. The nanodispersed TiO(2) on Au(111) is an ideal system to test the various models proposed for the enhanced catalytic reactivity of supported Au nanoparticles.     

Principle of a new immunoassay based on electrophoretic mobility of poly(styrene/alpha-tert-butoxy-omega-vinylbenzyl-polyglycidol) microspheres: application for the determination of helicobacter pylori IgG in blood serum

The principle of a novel latex diagnostic test for the determination of antibodies against Helicobacter pylori in blood sera is described. The test is based on the measurement of the electrophoretic mobility of the microspheres with immobilized H. pylori antigens. The electrophoretic mobility of these microspheres depends on the concentration of the antibodies against H. pylori in suspending medium. Particles with hydrophilic polyglycidol in the surface layer were used for the test. The microspheres were obtained by an emulsifier-free emulsion copolymerization of styrene and alpha-tert-butoxy-omega-vinylbenzyl-polyglycidol macromonomer (D(n) = 220 nm, diameter polydispersity factor D(w)//D(n) = 1.02). Activation of polyglycidol hydroxyl groups with cyanuric chloride allowed for covalent immobilization of H. pylori antigens. The fraction of H. pylori not specifically adsorbed onto the microspheres was negligible. Changes of the electrophoretic mobility of the microspheres with the surface concentration of the covalently immobilized H. pylori antigens Gamma = (1.6 +/- 0.3) . 10(-3) g m(-2) were suitable for the detection of the antibodies in the sera of patients with titer in the range (determined by the indirect ELISA test) from 1:500 to 1:32 000.     

ADLOC: An Aptamer‐Displacement Assay Based on Luminescent Oxygen Channeling

Functional nucleic acids, such as aptamers and allosteric ribozymes, can sense their ligands specifically, thereby undergoing structural alterations that can be converted into a detectable signal. The direct coupling of molecular recognition to signal generation enables the production of versatile reporters that can be applied as molecular probes for various purposes, including high‐throughput screening. Here we describe an unprecedented type of a nucleic acid‐based sensor system and show that it is amenable to high‐throughput screening (HTS) applications. The approach detects the displacement of an aptamer from its bound protein partner by means of luminescent oxygen channeling. In a proof‐of‐principle study we demonstrate that the format is feasible for efficient identification of small drug‐like molecules that bind to a protein target, in this case to the Sec7 domain of cytohesin. We extended the approach to a new cytohesin‐specific single chain DNA aptamer, C10.41, which exhibits a similar binding behavior to cytohesins but has the advantage of being more stable and easier to synthesize and to modify than the RNA‐aptamer M69. The results obtained with both aptamers indicate the general suitability of the aptamer‐displacement assay based on luminescent oxygen channelling (ADLOC) for HTS. We also analyzed the potential for false positive hits and identified from a library of 18 000 drug‐like small molecules two compounds as strong singlet‐oxygen quenchers. With full automation and the use of commercially available plate readers, we estimate that the ADLOC‐based assay described here could be used to screen at least 100 000 compounds per day.     

Hirshfeld surface analysis of two new phosphorothioic triamide structures

Hirshfeld surfaces and two‐dimensional fingerprint plots are used to analyse the intermolecular interactions in two new phosphorothioic triamide structures, namely N,N′,N′′‐tris(3,4‐dimethylphenyl)phosphorothioic triamide acetonitrile hemisolvate, P(S)[NHC₆H₃‐3,4‐(CH₃)₂]₃·0.5CH₃CN or C₂₄H₃₀N₃PS·0.5CH₃CN, (I), and N,N′,N′′‐tris(4‐methylphenyl)phosphorothioic triamide–3‐methylpiperidinium chloride (1/1), P(S)[NHC₆H₄(4‐CH₃)]₃·[3‐CH₃‐C₅H₉NH₂]⁺·Cl⁻ or C₂₁H₂₄N₃PS·C₆H₁₄N⁺·Cl⁻, (II). The asymmetric unit of (I) consists of two independent phosphorothioic triamide molecules and one acetonitrile solvent molecule, whereas for (II), the asymmetric unit is composed of three components (molecule, cation and anion). In the structure of (I), the different components are organized into a six‐molecule aggregate through N—H...S and N—H...N hydrogen bonds. The components of (II) are aggregated into a two‐dimensional array through N—H...S and N—H...Cl hydrogen bonds. Moreover, interesting features of packing arise in this structure due to the presence of a double hydrogen‐bond acceptor (the S atom of the phosphorothioic triamide molecule) and of a double hydrogen‐bond donor (the N—H unit of the cation). For both (I) and (II), the full fingerprint plot of each component is asymmetric as a consequence of the presence of three fragments. These analyses reveal that H...H interactions [67.7 and 64.3% for the two symmetry‐independent phosphorothioic triamide molecules of (I), 30.7% for the acetonitrile solvent of (I), 63.8% in the phosphorothioic triamide molecule of (II) and 62.9% in the 3‐methylpiperidinium cation of (II)] outnumber the other contacts for all the components in both structures, except for the chloride anion of (II), which only receives the Cl...H contact. The phosphorothioic triamide molecules of both structures include unsaturated C atoms, thus presenting C...H/H...C interactions: 17.6 and 21% for the two symmetry‐independent phosphorothioic triamide molecules in (I), and 22.7% for the phosphorothioic triamide molecule of (II). Furthermore, the N—H...S hydrogen bonds in both (I) and (II), and the N—H...Cl hydrogen bonds in (II), are the most prominent interactions, appearing as large red spots on the Hirshfeld surface maps. The N...H/H...N contacts in structure (I) are considerable, whereas for (II), they give a negligible contribution to the total interactions in the system.     

In vitro screening of the action of non-steroidal anti-inflammatory drugs on hypochlorous acid-induced hyaluronan degradation

The antioxidative effect of two non-steroidal anti-inflammatory drugs was studied in vitro by measuring the kinetics of degradation of high-molecular weight hyaluronan (HA) in a system comprising hypochlorous acid + CuCl₂ + ascorbic acid using a Brookfield rotational viscometer equipped with a Teflon cup and spindle of coaxial cylindrical geometry. The changes in HA chemical structure were investigated by chemiluminometry. When sodium naproxen was added to the system during a running degradative process its inhibitory effect was clearly shown. The inhibition was dependent on the drug concentration. However, when this drug was added to the system before the initiation of HA degradation, no inhibition was seen even at the highest drug concentration tested. The inhibitory effect of acetylsalicylic acid was achieved with a relatively low concentration of the drug and was independent of the experimental model used.     

Pulsed field gradient NMR study of phenol binding and exchange in dispersions of hollow polyelectrolyte capsules

The distribution and exchange dynamics of phenol molecules in colloidal dispersions of submicron hollow polymeric capsules is investigated by pulsed field gradient NMR (PFG-NMR). The capsules are prepared by layer-by-layer assembly of polyelectrolyte multilayers on silica particles, followed by dissolution of the silica core. In capsule dispersion, (1)H PFG echo decays of phenol are single exponentials, implying fast exchange of phenol between a free site and a capsule-bound site. However, apparent diffusion coefficients extracted from the echo decays depend on the diffusion time, which is typically not the case for the fast exchange limit. We attribute this to a particular regime, where apparent diffusion coefficients are observed, which arise from the signal of free phenol only but are influenced by exchange with molecules bound to the capsule, which exhibit a very fast spin relaxation. Indeed, relaxation rates of phenol are strongly enhanced in the presence of capsules, indicating binding to the capsule wall rather than encapsulation in the interior. We present a quantitative analysis in terms of a combined diffusion-relaxation model, where exchange times can be determined from diffusion and spin relaxation experiments even in this particular regime, where the bound site acts as a relaxation sink. The result of the analysis yields exchange times between free phenol and phenol bound to the capsule wall, which are on the order of 30 ms and thus slower than the diffusion controlled limit. From bound and free fractions an adsorption isotherm of phenol to the capsule wall is extracted. The binding mechanism and the exchange mechanism are discussed. The introduction of the global analysis of diffusion as well as relaxation echo decays presented here is of large relevance for adsorption dynamics in colloidal systems or other systems, where the standard diffusion echo decay analysis is complicated by rapidly relaxing boundary conditions.