Intercepting bacterial indole signaling with flustramine derivatives

Indole signaling is one of the putative universal signaling networks in bacteria. We have investigated the use of desformylflustrabromine (dFBr) derivatives for the inhibition of biofilm formation through modulation of the indole-signaling network in Escherichia coli and Staphylococcus aureus . We have found dFBr derivatives that are 10-1000 times more active than indole itself, demonstrating that the flustramine family of indolic natural products represent a privileged scaffold for the design of molecules to control pathogenic bacterial behavior.     

Synthesis of N2-alkyl-8-oxo-7,8-dihydro-2'-deoxyguanosine derivatives and effects of these modifications on RNA duplex stability

N(2)-alkyl analogues of 8-oxo-7,8-dihydro-2'-deoxyguanosine (OG) were synthesized (alkyl = propyl, benzyl) via reductive amination of the protected OG nucleoside and incorporated into various positions of an RNA strand. Thermal stability studies of duplexes containing A or C opposite a single modified base revealed only moderate destabilization. Both OG as well as its N(2)-alkyl analogues can pair opposite A or C with nearly equal stability, potentially offering a new means of modulating RNA-protein interactions in the minor vs major grooves.     

Influence of surfactant concentration on the surface morphology of hollow silica microspheres and its explanation

The surface morphology of hollow silica microspheres has influence on their applications. After a thorough investigation of the deposition of silica nanoparticles on polystyrene (PS) beads and the surface morphology and texture of the resultant hollow silica shells with scanning electron microscopy, transmission electron microscopy, and N2-sorption measurements, the influence of surfactant [cetyltrimethylammonium bromide (CTAB)] concentration on the surface morphology of hollow silica microspheres templated by PS beads is explained. Previously, CTAB was believed to turn the surface charge of PS beads from negative into positive so that negatively charged silica could be deposited on the PS template. Here, we show CTA+ cations preferentially assemble with silica species to form silica-CTA+ composite nanoparticles. Since the zeta potential of silica-CTA+ composite nanoparticles is smaller than that of pure silica nanoparticles, these composite nanoparticles encounter less repulsion when they are deposited on the surface of PS beads and close to each other. As more CTAB is added, the silica-CTA+ nanoparticles are less negatively charged, and more compact and smooth hollow silica microspheres are obtained.     

Diffusion of gases across lipid membranes with OmpA channel: a molecular dynamics study

Molecular transport across biological membranes occurs in a range of important chemical and biological processes. The biological membrane can usually be modelled as a phospholipid bilayer, but to correctly represent biological transport, the embedded transmembrane proteins must also be included. In previous molecular simulation studies on transport of small gas molecules in dipalmitoylphosphatidylcholine (DPPC) bilayer membrane, a coarse-grained model was used to provide direct insight into collective phenomena in biological membranes. Coarse graining allowed investigation of longer time and length scales by reducing the degrees of freedom and employing suitable potentials. In this work, membranes that include transmembrane proteins are modelled. This allows one to compare the molecular transport across a lipid membrane with and without the assistance of transmembrane channels. Outer membrane protein A (OmpA) – a porin from Escherichia coli with a small pore size – was chosen in this study because its detailed structure is known, it has high stability and is known to form a nonspecific diffusion channel that permits the penetration of various solutes. In this work the pore characteristics and interaction between lipid and protein were investigated and transport of water and other small gas molecules within the channel were studied. The MD simulation results obtained are compared with previous simulation results and available experimental data. The results obtained from this study will lead to better understanding of protein functionality and advance the development of biochips and drug delivery systems.     

Role of Alginate Composition on Copper Ion Uptake in the Presence of Histidine or Beta-Amyloid

The anomalous interaction between metal ions and the peptide beta-amyloid is one of the hallmarks of Alzheimer’s disease. Metal-binding biopolymers, including polysaccharides, can elucidate the fundamental aspects of metal ions’ interactions with biological tissue and their interplay in Alzheimer’s disease. This work focuses on the role of the alginate composition on Cu(II) adsorption in the presence of histidine or β-amyloid, the peptide associated with the progression of Alzheimer’s disease. Alginate samples with different mannuronic/guluronic (M/G) ratios led to similar Cu(II) adsorption capacities, following the Langmuir isotherm and the pseudo-second-order adsorption kinetic models. Although the presence of histidine produced up to a 20% reduction in the copper adsorption capacity in guluronic-rich alginate samples (M/G~0.61), they presented stable bidentate chelation of the metallic ion. Chemical analyses (FTIR and XPS) demonstrated the role of hydroxyl and carboxyl groups in copper ion chelation, whereas both crystallinity and morphology analyses indicated the prevalence of histidine interaction with guluronic-rich alginate. Similar results were observed for Cu(II) adsorption in alginate beads in the presence of beta-amyloid and histidine, suggesting that the alginate/histidine system is a simple yet representative model to probe the application of biopolymers to metal ion uptake in the presence of biological competitors.     

Novel route to 5-position vinyl derivatives of thiolactomycin: Olefination vs. deformylation

Vinyl and diene derivatives of thiolactomycin have been prepared via Horner-Wadsworth-Emmons olefination from protected 5-formyl-3,5-dimethylthiotetronic acid. Several 4-position protecting groups and a variety of phosphonates were evaluated, with MOM protection and β-ketophosphonates yielding the highest ratio of the desired product to deformylated product.     

Influence of surfactant addition on the stability of concentrated alumina dispersions in water

The goal of this study was to assess the effects of surfactant addition on the stability and viscosity of concentrated alumina dispersions. The stabilizing effects of several candidate surfactants were investigated for concentrated dispersions of two different pseudoboehmite aluminas at pH 4 and 7. The stabilities of concentrated alumina dispersions treated by pH adjustment alone and by pH adjustment combined with surfactant addition were compared to assess the degree to which the surfactant enhanced stability. The initial rate of mass removal from a sedimenting alumina dispersion was used as a measure of stability.

The anionic surfactants Surfine WNT-A and DOWFAX 3B2 were identified as effective in enhancing the stability of concentrated alumina dispersions. The optimal doses of these surfactants for stabilizing 15% by weight VERSAL™ 250 alumina dispersions at pH 4 were determined to be about 4.6 × 10⁻⁵ mol g⁻¹ for both surfactants. On the basis of the initial rate of mass removal, surfactant-stabilized 15 wt.% suspensions were found to be approximately 2.5 and 10.6 times more stable than similar dispersions stabilized electrostatically by pH adjustment alone. These more stable dispersions exhibited lower viscosities than observed for the alumina dispersions not subjected to surfactant addition. The results indicate that the stability of concentrated alumina dispersions can be enhanced by anionic surfactant addition, and that such surfactants may therefore help to control the rheology of concentrated dispersions of alumina in water.     

Clean-up method for determination of established and emerging brominated flame retardants in dust

A clean-up method was developed to enable the determination of tri-decabrominated diphenyl ethers, isomer-specific hexabromocyclododecanes (HBCDs), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), (2-ethylhexyl)tetrabromobenzoate (TBB), and bis(2-ethylhexyl)tetrabromophthalate (TBPH) in the same dust sample extract using reasonable amounts of solvents and without dividing the sample. After extraction, the sample was separated on a silica column into three fractions that were subsequently cleaned up individually. The polybrominated diphenyl ethers (PBDEs) and DBDPE were eluted in Fraction I, TBB, TBPH, and BTBPE in Fraction II, and HBCDs in Fraction III. Fractions I and II were analyzed using gas chromatography/mass spectrometry and Fraction III using liquid chromatography/mass spectrometry. The method gave good recoveries (60-120%), precise results using (13)?C-labelled internal standards and was accurate when comparing results to certified values (PBDEs in NIST SRM 2585). The method was applied to dust samples from the Stockholm (Sweden) area. All the emerging brominated flame retardants (BFRs) studied, except BTBPE, were present in all the samples in quantifiable concentrations, often higher than the PBDEs. BTBPE was quantified in only one sample. It is evident that emerging BFRs are present in Swedish homes, and these compounds should be included in the BFR analyses of indoor environments.     

SULFOPHTHALOCYANINES FOR PHOTODYNAMIC INACTIVATION OF VIRUSES IN BLOOD PRODUCTS: EFFECT OF STRUCTURAL MODIFICATIONS

Abstract— Transmission of infectious diseases through blood transfusions is well known. Ultraviolet irradiation, solvents and detergents provide a means of sterilizing noncellular blood components. However these harsh methods are not applicable to cellular blood products. Recently, attempts have been made to sterilize biological fluids using photodynamic treatment and phthalocyanine (Pc) dyes have been advanced as photosensitizers for this purpose. We have evaluated a series of water-soluble Pc, chelated with different central metal ions, substituted to different degrees with sulfonato and r-butyl groups, for their effectiveness to reduce virus infectivity in red blood cell suspensions. Vaccinia virus cytopathogenicity was determined by endpoint serial dilutions in the CV-1 cell line. Anti-viral activity increased with the central metal ion in the following order: Ga(III) < Al(III) < Zn(II), and varied inversely with the degree of sulfonation. Furthermore, addition of a t -butyl group onto the trisulfonated dyes (PcS₃[ t -Bul) resulted in a 5–40-fold increase in anti-viral potency, suggesting that amphiphilicity enhances the photodynamic activity of the dye. Strong anti-viral photosensitizing properties cannot be the sole selection criterion. Of equal importance is the preservation of blood component integrity. Accordingly, the photohemolytic activity of the dyes was evaluated using the rate of hemolysis as a parameter and a toxicity index was defined. Among the most active dyes, the AlPcS₃( t -Bu) complex exhibited the most favorable anti-viral properties combined with a low toxicity index. Our results suggest that trisulfophthalocyanines, bearing an additional t -butyl group to enhance amphiphilicity, are particularly promising dyes for photodynamic blood sterilization.     

Resolution of (R,S)-flurbiprofen catalysed by dry mycelia in organic solvent

Mycelia of Aspergillus oryzae display high enantioselectivity towards (R)-flurbiprofen and can be efficiently used in pure organic solvent for the resolution of (R,S)-flurbiprofen through esterification. The use of the lyophilized mycelia facilitates the separation process so that in one step the two enantiomers of flurbiprofen, which are both valuable for pharmaceutical applications, can be easily separated. The biotransformation can be carried out in different apolar solvents using different primary alcohols as nucleophiles under very mild conditions.