John P. H. Wilding (ed): Pharmacotherapy of obesity (MDT: Milestones in Drug Therapy Series) Birkhäuser Verlag AG, Basel, Switzerland, 2008, 132 p, Hardcover, ISBN 978-3-7643-7138-8

A review of Pharmacotheraphy of obesity

Quantification of functionalised gold nanoparticle-targeted knockdown of gene expression in HeLa cells

Introduction: Gene therapy continues to grow as an important area of research, primarily because of its potential in the treatment of disease. One significant area where there is a need for better understanding is in improving the efficiency of oligonucleotide delivery to the cell and indeed, following delivery, the characterization of the effects on the cell. Methods: In this report, we compare different transfection reagents as delivery vehicles for gold nanoparticles functionalized with DNA oligonucleotides, and quantify their relative transfection efficiencies. The inhibitory properties of small interfering RNA (siRNA), single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA) sequences targeted to human metallothionein hMT-IIa are also quantified in HeLa cells. Techniques used in this study include fluorescence and confocal microscopy, qPCR and Western analysis. Findings: We show that the use of transfection reagents does significantly increase nanoparticle transfection efficiencies. Furthermore, siRNA, ssRNA and ssDNA sequences all have comparable inhibitory properties to ssDNA sequences immobilized onto gold nanoparticles. We also show that functionalized gold nanoparticles can co-localize with autophagosomes and illustrate other factors that can affect data collection and interpretation when performing studies with functionalized nanoparticles. Conclusions: The desired outcome for biological knockdown studies is the efficient reduction of a specific target; which we demonstrate by using ssDNA inhibitory sequences targeted to human metallothionein IIa gene transcripts that result in the knockdown of both the mRNA transcript and the target protein. © 2014 Jiwaji et al.

Synthesis and evaluation of nanoparticle-polymer composites

This thesis describes the synthesis of functionalised polymeric material by variety of free-radical mediated polymerisation techniques including dispersion emulsion, seeded emulsion, suspension and bulk polymerisation reactions. Organic fluorophores and nanoparticles such as quantum dots were incorporated within polymeric materials, in particular, thiol-functionalised polymer microspheres, which were fluorescently labelled either during synthesis or by covalent attachment post synthesis. The resultant fluorescent polymeric conjugates were then assessed for their utility in biological systems as an analytical tool for cells or biological structures. Quantum dot labelled, thiol-functionalised microspheres were assessed for their utility in the visualisation and tracking of red blood cells. Determination of the possible internalisation of fluorescent microspheres into red blood cells was required before successful tracking of red blood cells could take place. Initial work appeared to indicate the presence of fluorescent microspheres inside red blood cells by the process of beadfection. A range of parameters were also investigated in order to optimise beadfection. Thiol-functionalised microspheres labelled successfully with organic fluorophores were used to image the tear film of the eye. A description of problems encountered with the covalent attachment of hydrophilic, thiol-reactive fluorescent dyes to a variety of modified polymer microspheres is also included in this section. Results indicated large microspheres were particularly useful when tracking the movement of fluid along the tear meniscus. Functional bulk polymers were synthesised for assessment of their interaction with titanium dioxide nanoparticles. Thiol-functionalised polymethyl methacrylate and spincoated thiouronium-functionalised polystyrene appeared to facilitate the attachment of titanium dioxide nanoparticles. Interaction assays included the use of XPS analysis and processes such as centrifugation. Attempts to synthesise 4-vinyl catechol, a compound containing hydroxyl moieties with potential for coordination with titanium dioxide nanoparticles, were also carried out using 3,4-dihydroxybenzaldehyde as the starting material.

Ag alloyed Pd single-atom catalysts for efficient selective hydrogenation of acetylene to ethylene in excess ethylene

Semihydrogenation of acetylene in an ethylene-rich stream is an industrially important process. Conventional supported monometallic Pd catalysts offer high acetylene conversion, but they suffer from very low selectivity to ethylene due to overhydrogenation and the formation of carbonaceous deposits. Herein, a series of Ag alloyed Pd single-atom catalysts, possessing only ppm levels of Pd, supported on silica gel were prepared by a simple incipient wetness coimpregnation method and applied to the selective hydrogenation of acetylene in an ethylene-rich stream under conditions close to the front-end employed by industry. High acetylene conversion and simultaneous selectivity to ethylene was attained over a wide temperature window, surpassing an analogous Au alloyed Pd single-atom system we previously reported. Restructuring of AgPd nanoparticles and electron transfer from Ag to Pd were evidenced by in situ FTIR and in situ XPS as a function of increasing reduction temperature. Microcalorimetry and XANES measurements support both geometric and electronic synergetic effects between the alloyed Pd and Ag. Kinetic studies provide valuable insight into the nature of the active sites within these AgPd/SiO2 catalysts, and hence, they provide evidence for the key factors underpinning the excellent performance of these bimetallic catalysts toward the selective hydrogenation of acetylene under ethylene-rich conditions while minimizing precious metal usage.

Pabively Q-switched erbium-doped fiber laser using Fe3O4-nanoparticle saturable absorber

We experimentally demonstrate pabively Q-switched erbium-doped fiber laser (EDFL) operation using a saturable absorber (SA) based on Fe3O4 nanoparticles (FONPs). As a type of transition metal oxide, the FONPs have a large nonlinear optical response and fast response time. The FONPbased SA pobebes a modulation depth of 8.2% and nonsaturable absorption of 56.6%. Stable pabively Q-switched EDFL pulses with an output pulse energy of 23.76 nJ, a repetition rate of 33.3 kHz, and a pulse width of 3.2 μs were achieved when the input pump power was 110mW. The laser features a low threshold pump power of > 15mW.

Sonogashira cross-coupling and homocoupling on a silver surface:chlorobenzene and phenylacetylene on Ag(100)

Scanning tunneling microscopy, temperature-programmed reaction, near-edge X-ray absorption fine structure spectroscopy, and density functional theory calculations were used to study the adsorption and reactions of phenylacetylene and chlorobenzene on Ag(100). In the absence of solvent molecules and additives, these molecules underwent homocoupling and Sonogashira cross-coupling in an unambiguously heterogeneous mode. Of particular interest is the use of silver, previously unexplored, and chlorobenzene—normally regarded as relatively inert in such reactions. Both molecules adopt an essentially flat-lying conformation for which the observed and calculated adsorption energies are in reasonable agreement. Their magnitudes indicate that in both cases adsorption is predominantly due to dispersion forces for which interaction nevertheless leads to chemical activation and reaction. Both adsorbates exhibited pronounced island formation, thought to limit chemical activity under the conditions used and posited to occur at island boundaries, as was indeed observed in the case of phenylacetylene. The implications of these findings for the development of practical catalytic systems are considered.

Niobic acid nanoparticle catalysts for the aqueous phase transformation of glucose and fructose to 5-hydroxymethylfurfural

A family of bulk and SBA-15 supported peroxo niobic acid sols were prepared by peptisation of niobic acid precipitates with H2O2 as heterogeneous catalysts for aqueous phase glucose and fructose conversion to 5-hydroxymethylfurfural (5-HMF). Niobic acid nanoparticles possess a high density of Brønsted and Lewis acid sites, conferring good activity towards glucose and fructose conversion, albeit with modest 5-HMF yields under mild reaction conditions (100 °C). Thermally-induced niobia crystallisation suppresses solid acidity and activity. Nanoparticulate niobic acid dispersed over SBA-15 exhibits pure Brønsted acidity and an enhanced Turnover Frequency for fructose dehydration.