Self-assembled and self-sorted array of chemically active beads for analytical and biochemical screening

A technique for generating a general screening platform consisting of dots of immobilized beads on silicon has been developed via self-sorting and -assembly of different kinds of beads. The dots are defined by a teflon-like film, which due to its hydrophobic characteristics also prevents cross-contamination of liquid from different dots. To enable functionalization of individual dots with different target molecules simultaneously a new way of microcontact printing has been explored where different target solutions are printed in parallel using one stamp. In order to show that this platform can be designed for both biochemical assays and organic chemistry, streptavidin-, amino- and hydroxy-functionalized beads have been self-sorted and -assembled both on separate and common platforms. The self-sorting and -arrangement are based on surface chemistry only, which has not previously been reported. Beads of different sizes and material have successfully been immobilized in line patterns as narrow as 5 mum. Besides silicon, quartz and polyethylene have also been used as substrates.     

Selective reagents for solvent extraction of metals—I. Quinaldic acids

Alkyl- and alkoxy-substituted quinoline-2-carboxylic acids were synthesized and tested for metal extraction. Zn²⁺ and Cu²⁺ were extracted from aqueous sulphate solutions by reagents containing 8-alkoxy substituents at lower pH values than were Fe²⁺ or Fe³⁺. Reagents without this substituent were unselective in this respect. A possible explanation for the selectivity may be that the 8-substituent influences the coordination geometry of the metal chelates in favour of tetrahedral complexes.     

Control of a multisubunit DNA motor by a thermoresponsive polymer switch

The conjugation of thermoresponsive polymers to multisubunit, multifunctional hybrid type 1 DNA restriction-modification (R-M) enzymes enables temperature-controlled "switching" of DNA methylation by the conjugate. Polymers attached to the enzyme at a subunit distal to the methylation subunit allow retention of DNA recognition and ATPase activity while controlling methylation of plasmid DNA. This regulation of enzyme activity arises from the coil-globule phase transitions of the polymer as shown in light scattering and gel retardation assays.     

Non-equilibrium cooling of Poncirus trifoliata (L.) embryonic axes at various water contents

The present study investigated the rate of temperature change within axes of Poncirus trifoliata during cooling and warming by various methods. Cooling rates ranged between 0.17 and 170 degree (C per second, and warming rates of 1.25 and 600 degree C per second were measured when axes were warmed at room temperature or in water at 40 degree C, respectively. Partial drying increased the cooling rate within axes in direct contact with the cryogen, but did not affect the cooling or warming rates within axes enclosed in a double layer of lightweight aluminium foil. The procedures described illustrate the orders of magnitude that separate extremes of the range of cooling or warming rates attained using methods commonly employed in cryopreservation studies. Quantifying these rates allows the relationship between cooling rate, water content and survival of hydrated embryonic axes to be explored.     

Universal covers for Hausdorff limits of noncompact spaces

We prove that if is the Gromov-Hausdorff limit of a sequence of complete manifolds, , with a uniform lower bound on Ricci curvature, then has a universal cover.

     

Development of small molecules that mimic the binding of ω-conotoxins at the N-type voltage-gated calcium channel

Cone snails (Conidae) are marine predators with some extraordinary features. Their venom contains a hundred or more peptides that target numerous ion channels and receptors in mammals, including several that are involved in disease. omega-Conotoxins from fish hunting snails are 24-27 residue peptides with a rigid 4-loop cysteine framework that target the N-type voltage-gated calcium channel (VGCC). Two omega-conotoxins, MVIIA and CVID are currently in clinical development for chronic pain management (Ziconotide or Prialt, and AM336, respectively). In an attempt to develop small molecule equivalents of CVID, we defined the Calpha-Cbeta vectors of the residues believed to be important for binding to the N-type VGCC. Using these vectors, we undertook a virtual screening of virtual libraries approach to identify compounds that matched the pharmacophore. Cyclic pentapeptides containing residues of loop 2 of CVID, with one or more being a D-amino acid were designed and synthesised and were found to be active at the N-type VGCC (IC50 approximately 20 microM). Agreeing with the specificity profile of CVID, molecules were inactive at the P/Q-type VGCC.     

Bidentate NHC-based chiral ligands for efficient Cu-catalyzed enantioselective allylic alkylations: structure and activity of an air-stable chiral Cu complex

Cu-catalyzed addition of alkylzinc reagents to a range of allylic phosphates is promoted efficiently and with high enantioselectivity to afford tertiary as well as quaternary carbon centers (up to 98% ee). Reactions proceed to completion with 0.5-5 mol % catalyst loading and are best promoted by commercially available CuCl2.2H2O. The X-ray structure of the chiral NHC-Ag(I) complex used in the study as well as that of a catalytically active NHC-Cu(II) complex are also reported; both complexes are air-stable and are formed in >/=95% isolated yield. The isolated Cu complex, which can be handled in air, is catalytically active. The present report provides the first precedent for efficient Cu-catalyzed allylic alkylations with chiral NHC ligands.