Virtual hydrocarbon and combinatorial databases for use with CAVEAT

Three new virtual databases have been developed for use with the bond-orientation-based database searching program CAVEAT. These consist of a database of trisubstituted monocyclic hydrocarbons having ethyl, vinyl, and phenyl substituents; a database of unsubstituted bicyclic hydrocarbons; and a database of core structures from established combinatorial synthetic methods having hydrogen, ethyl, vinyl, and phenyl substituents at the readily varied positions. Each collection of molecules was subjected to a batch conformational search, minimization, and conversion to a vector database for use with CAVEAT.     

Mechanistic divergence of two closely related aldol-like enzyme-catalysed reactions

The analysis of the interaction of threose 4-phosphate and 2-deoxyerythrose 4-phosphate with 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) reveals previously unrecognised mechanistic differences between the DAH7PS-catalysed reaction and that catalysed by the closely related enzyme, 3-deoxy-D-manno-octulosonate 8-phosphate synthase (KDO8PS).     

Identification of 5-fluoro-5-deoxy-D-ribose-1-phosphate as an intermediate in fluorometabolite biosynthesis in Streptomyces cattleya

5'-Fluoro-5'-deoxy-D-ribose-1-phosphate (FDRP) is identified as a biosynthetic intermediate during fluorometabolite biosynthesis in Streptomyces cattleya.     

PtCl2-catalyzed cycloisomerizations of 5-en-1-yn-3-ol systems

5-En-1-yn-3-ol substrates bearing a free hydroxyl group or an acyl group are highly versatile partners for PtCl2-catalyzed cycloisomerizations. Electrophilic activation of the alkyne moiety triggers at wish a hydride or an O-acyl migration yielding at the end to regioisomeric keto derivatives. The efficient preparation of Sabina ketone, an important monoterpene precursor, has been worked out.     

Chiral proton catalysis: a catalytic enantioselective direct aza-Henry reaction

Despite Nature's longstanding ability to use a proton, the most prevalent Lewis acid, to both activate and orient a substrate during an enantioselective reaction, this work represents the first example of this phenomenon outside of a protein. A chiral, nonracemic BisAMidine (BAM) ligand was designed, synthesized, and complexed to the proton of a Br?nsted acid. The resulting coordination compound catalyzed the production of enantioenriched product from the combination of a Schiff base and nitroalkane (the aza-Henry reaction). This particular reaction is also considered a model for many analogous carbon-carbon bond-forming reactions catalyzed by enzymes (e.g., the Mannich reaction). This discovery suggests the use of ionic hydrogen bonds in asymmetric catalysis may not only be more general than previously thought, but also a viable "green" approach to single-enantiomer organic compounds.     

Compatibility of mammalian cells on surfaces of poly(dimethylsiloxane)

This paper describes the influence of the composition of poly(dimethylsiloxane) (PDMS) on the attachment and growth of several different types of mammalian cells: primary human umbilical artery endothelial cells (HUAECs), transformed 3T3 fibroblasts (3T3s), transformed osteoblast-like MC3T3-E1 cells, and HeLa (transformed epithelial) cells. Cells grew on PDMS having different ratios of base to curing agent: 10:1 (normal PDMS, PDMSN), 10:3 (PDMSCA), and 10:0.5 (PDMSB). They were also grown on "extracted PDMS" (normal PDMS that has reduced quantities of low molecular-weight oligomers, PDMSN,EX) and normal PDMS that had been extracted and then oxidized (PDMSN,EX,OX); all surfaces were exposed to a solution of fibronectin prior to cell attachment. Generally, fibronectin-coated PDMS is a suitable substrate for culturing mammalian cells. Compatibility of cells on some surfaces, however, was dependent on the cell type: PDMSN,EX,OX caused cell detachment of 3T3 fibroblasts and MC3T3-E1 cells, and PDMSCA caused detachment of HUAECs and HeLa cells. Growth of cells on PDMSN, PDMSN,EX, and PDMSB was comparable to growth on tissue culture-treated polystyrene for most of the cell types. All cells grew at similar rates on PDMS substrates regardless of the stiffness of the substrate, for substrates having Young's moduli ranging from E=0.60 +/- 0.04 to 2.6 +/- 0.2 MPa (for PDMSB and PDMSN,EX, respectively).     

Vinyl sulfones: inhibitors of SrtA, a transpeptidase required for cell wall protein anchoring and virulence in Staphylococcus aureus

Several small molecule vinyl sulfones were found to exhibit irreversible time-dependent inhibition of the Staphylococcus aureus sortase SrtA in vitro. A representative of these compounds was shown to impair the ability of S. aureus bacteria to bind fibronectin-coated surfaces through in vivo inhibition of SrtA-mediated linkage of fibronectin to the cell surface. These data highlight the potential use of small molecule vinyl sulfones as chemotherapeutics to prevent adhesion to and colonization of host tissues during S. aureus infection.     

Investigation of modified basal plane pyrolytic graphite electrodes: definitive evidence for the electrocatalytic properties of the ends of carbon nanotubes

The basis of the electrocatalytic nature of multi-wall carbon nanotubes is suggested to reside in electron transfer from the ends of nanotubes, which structurally resemble the behaviour of edge plane (as opposed to basal plane) graphite, and is demonstrated via the comparison of the electrochemical oxidation of epinephrine and the electrochemical reduction of ferricyanide at nanotube-modified electrodes using different types of graphite electrodes and with C(60)-modified electrodes.     

Development of a cryopreservation protocol for the microcyclic rust-fungus Puccinia spegazzinii

The rust fungus Puccinia spegazzinii (Basidiomycotina: Uredinales) has been identified as a potential classical biological control agent for the invasive weed Mikania micrantha (Asteraceae). Long-term, live storage of this pathogen is required for reference. As biotrophs, almost all rusts species cannot be preserved by traditional cryopreservation protocols, which rely on in vitro culture techniques. In addition, the embedded teliospores and delicate basidiospores of this microcyclic rust are not amenable to direct plunge freezing. Continuous culture of the rust on living plants is both laborious and expensive, so a variety of approaches for cryopreservation and storage were tested. These methods included traditional approaches to fungal cryopreservation such as variation of cooling rate regime and alginate encapsulation techniques. However, an in situ cryopreservation technique was the only method identified as having any potential for the long-term cryopreservation of the 10 isolates tested. Material from either petiole or stem tissue remained viable after cryopreservation, determined by the ability of the material to produce basidiospores. However, despite great progress being made in developing an optimal cryopreservation method, infection of the host plant by basidiospores produced from previously cryopreserved teliospores, embedded in leaf petioles, was not achieved.     

Anechoic chamber qualification: traverse method,inverse square law analysis method,and nature of test signal

Qualification of anechoic chambers is intended to demonstrate that the chamber supports the intended free-field environment within some permissible tolerance bounds. Key qualification issues include the method used to obtain traverse data, the analysis method for the data, and the use of pure tone or broadband noise as the chamber excitation signal. This paper evaluates the relative merits of continuous versus discrete traverses, of fixed versus optimal reference analysis of the traverse data, and of the use of pure tone versus broadband signals. The current practice of using widely space discrete sampling along a traverse is shown to inadequately sample the complexity of the sound field extant with pure tone traverses, but is suitable for broadband traverses. Continuous traverses, with spatial resolution on the order of 15% of the wavelength at the frequency of interest, are shown to be necessary to fully resolve the spatial complexity of pure tone qualifications. The use of an optimal reference method for computing the deviations from inverse square law is shown to significantly improve the apparent performance of the chamber for pure tone qualifications. Finally, the use of broadband noise as the test signal, as compared to pure tone traverses over the same span, is demonstrated to be a marginal indicator of chamber performance.