Development of methodology and novel composite electrodes for the selective electrochemical fluorination of organic compounds for use in positron emission tomography

PhD ThesisThe search for fast, safe and selective fluorination protocols has been the focus of much research in recent years as a result of the unique biological and functional properties afforded by fluorinated organic compounds, and the hazards associated with their production by traditional methods. The need for improved methodologies is especially great for the synthesis of fluorine-18 compounds, owing to the relatively short half-life of the isotope (109.7 min). One technique that could be utilised as a viable synthetic tool is electrochemical fluorination (ECF). Historically, ECF has been researched by a relatively small number of groups; consequently, the technique is not fully understood and is often overlooked by synthetic chemists. In order to make ECF a viable method for routine fluorination of organic compounds, more work is required to understand the full potential of the technique, and the mechanisms by which it occurs. In addition to this, the development of new technologies is essential to further improve control and selectivity of ECF reactions, and hence maximise the potential of the technique. This thesis is split into two main sections; the first details an investigation into the electrochemical fluorination (ECF) of organic compounds, including some aromatic substrates, with a particular focus on the ECF of cyclic carbonates, as these provide good models for electron-rich aliphatic molecules, the like of which are typically difficult to fluorinate by traditional nucleophilic methods. The effects of electrolyte and current density on the overall yield and distribution of fluorinated products has been investigated for the selective ECF of ethylene carbonate using the molten salt electrolytes Et4NF.3HF and Et4NF.4HF. The optimum conditions were then applied to the ECF of propylene carbonate, displaying the first synthesis of the mono-fluorinated product, 4-fluoro-4-methyl- 1,3-dioxolan-2-one (6) by a reaction that has not been reported previously. The main products of each reaction were characterised fully by NMR for the first time, highlighting the interesting AA`XX` spin system displayed by the di-fluorinated compounds (3) and (4). In-situ electrochemical electron pair resonance (EPR) spectroscopy was performed in an attempt to elucidate the mechanism by which ECF occurs. The results of these studies were inconclusive; however, a radical-cation mechanism is postulated, based on a combination of molecular modelling calculations and literature. The second section is concerned with the development of a completely new type of composite electrode which could potentially allow greater control of regioselectivity in ECF reactions as well as expanding the number of substrates to which the technique can be applied. The composite anodes are comprised of a TiO2 doped Si substrate upon which is deposited a metal grid. A battery connected between the metal grid and the back of the Si wafer allow a flow of electrons through the device (providing the bias circuit) in addition to the standard electrochemical circuit. The application of bias potential allows increased currents at lower electrochemical potentials. Fundamental investigation into the electrochemical behaviour of the anodes resulted in the postulation of a theoretical model detailing the mechanism by which the anodes work. The model is based on the theory of hole generation and transport through the device by means of Anderson localisation and Miller-Abrahams hopping. It was found that irradiation of the anode surface further increased bias current, hence affording greater control by presenting a three-dimensional surface on which to operate, as opposed to a one-dimensional axis, as is the case with conventional electrodes.EPSRC

Lymphatic Filariasis (Elephantiasis) Elimination: A public health success and development opportunity

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis, launched following World Health Assembly Resolution 50.29 (WHA 50.29), has been facilitated in its progress by new research findings, drug donations, the availability of diagnostic tools, disability management strategies to help those already suffering and the development of partnerships. The strategy recommended by the World Health Organization of annual treatment with a two-drug combination has proved safe. DISCUSSION: Using different approaches in several countries the elimination of lymphatic filariasis (LF) has been demonstrated to be feasible during earlier decades. These successes have been largely overlooked. However, the programme progress since 2000 has been remarkable – upscaling rapidly from 2 million treatments in 2000 to approximately 60 million in 2002. Around 34 countries had active programmes at the end of 2002. It is anticipated that there will be further expansion – but this will be dependent on additional resources becoming available. The programme also provides significant opportunities for other disease control programmes to deliver public health benefits on a large scale. Few public health programmes have upscaled so rapidly and so cost-effectively (<$0.03/treatment in some Asian settings) – one country treating 9–10 million people in a day (Sri Lanka). The LF programme is arguably the most effective pro-poor public health programme currently operating which is based on country commitment and partnerships supported by a global programme and alliance. Tables are provided to summarize programme characteristics, the benefits of LF elimination, opportunities for integration with other programmes and relevance to the Millennium Development Goals. SUMMARY: Lymphatic filariasis elimination is an "easy-to-do" inexpensive health intervention that provides considerable "beyond filariasis" benefits, exemplifies partnership and is easily evaluated. The success in global health action documented in this paper requires and deserves further support to bring to fruition elimination of lymphatic filariasis as a public health problem and health benefits to poor people. A future free of lymphatic filariasis will reduce poverty and bring better health to poor people, prevent disability, strengthen health systems and build partnerships

Efficiency and risk in european banking

We analyze the impact of efficiency on bank risk. We also consider whether bank capital has an effect on this relationship. We model the inter-temporal relationships among efficiency, capital and risk for a large sample of commercial banks operating in the European Union. We find that reductions in cost and revenue efficiencies increase banks’ future risks thus supporting the bad management and efficiency version of the moral hazard hypotheses. In contrast, bank efficiency improvements contribute to shore up bank capital levels. Our findings suggest that banks lagging behind in their efficiency levels might expect higher risk and subdued capital positions in the near future. JEL Classification: G21, D24, C23, E44banking risk, capital, Efficiency

Cross-Country Comparisons of Competition and Pricing Power in European Banking

Studies of banking competition and competitive behaviour both within and across countries typically utilise only one of the few measures that are available. In trying to assess the relative competitive position of banking markets in 14 European countries, we find that the existing indicators of competition often give conflicting predictions, both across countries and over time. Seeking greater consistency, we attempt to separate bank pricing power from other, non-core, influences embodied in competition measures. While there is some improvement in cross-country consistency, the main result is that our measure of bank pricing power suggests that banking market competition in Europe may well be stronger than implied by traditional measures and analysis.Competition; banking

Development of a new running gear for the Spectrum intermodal vehicle

The European Union (EU) Seventh Framework Programme (FP7) project Spectrum [12] set out to develop a freight vehicle which would facilitate the exploitation of the low density, high value (LDHV) goods market. Key to the performance criteria for the vehicle were: increased speed to enable mixed running with passenger services; improved ride quality to avoid damage to the LDHV goods; and reduced track damage for longevity and sustainability on increasingly stressed infrastructure. This paper presents aspects of the development of a novel running gear arrangement for the Spectrum vehicle, focussing on the dynamic performance of a Vampire vehicle model and the steps to realising stable running. Finally, the estimated performance of the Spectrum vehicle concept is compared against calculations for a conventional freight wagon with respect to curving, vertical track forces and potential savings in track access charges through implementation of Network Rail’s Variable Track Access Charge Calculator. It was found that the novel Spectrum concept could offer savings in Variable Usage Charges of between 8% and 16% compared to the conventional equivalent

Environmental factors associated with the distribution of Loa loa vectors Chrysops spp. in Central and West Africa: seeing the forest for the trees

Background Loiasis is caused by the filarial parasite Loa loa, which is widespread through Central and West Africa and largely confined the tropical equatorial rainforests. The tabanid flies Chrysops silacea and Chrysops dimidiata are the main vectors driving transmission. This study aimed to better define the spatial distribution and ecological niche of the two vectors to help define spatial-temporal risk and target appropriate, timely intervention strategies for filariasis control and elimination programmes. Methods Chrysops spp. distributions were determined by collating information from the published literature into a database, detailing the year, country, locality, latitude/longitude and species collected. Environmental factors including climate, elevation and tree canopy characteristics were summarised for each vector from data obtained from satellite modelled data or imagery, which were also used to identify areas with overt landcover changes. The presence of each Chrysops vector was predicted using a maximum entropy species distribution modelling (MaxEnt) method. Results A total of 313 location-specific data points from 59 published articles were identified across seven loiasis endemic countries. Of these, 186 sites were included in the climate and elevation analysis, and due to overt landcover changes, 83 sites included in tree canopy analysis and MaxEnt model. Overall, C. silacea and C. dimidiata were found to have similar ranges; annual mean temperature (24.6 °C and 24.1 °C, respectively), annual precipitation (1848.6 mm and 1868.8 mm), elevation (368.8 m and 400.6 m), tree canopy cover (61.4% and 66.9%) and tree canopy height (22.4 m and 25.1 m). MaxEnt models found tree canopy coverage was a significant environmental variable for both vectors. Conclusions The Chrysops spp. database and large-scale environmental analysis provides insights into the spatial and ecological parameters of the L. loa vectors driving transmission. These may be used to further delineate loiasis risk, which will be important for implementing filariasis control and elimination programmes in the equatorial rainforest region of Central and West Africa

The Spectrum Bogie

This poster, providing an overview of the Spectrum freight bogie, was presented at the Railway Engineers Forum (REF) Technical Seminar held at the Institution of Civil Engineers on the 15th June 2015