Marine polycyclic ethers are natural products isolated from marine plankton dinoflagellates such as Gambierdiscus toxicus and Karenia breve. They possess characteristic flat, semi-rigid, ladder-like structures and represent some of the largest, and most toxic, non-polymeric natural products discovered to date. Seafood contaminated with minute quantities of polycyclic ethers causes ciguatera, a debilitating illness that has been reported to last for more than 20 years. The first chapter of this thesis provides an introduction to marine polycyclic ethers, detailing their origins, biosynthesis and mechanism of action. Prior syntheses of members of the ciguatoxin family by Hirama, Isobe, Kadota and Fujiwara are reviewed, with focus on the cyclisation strategies employed by each group. The methodology and two-directional strategies developed by the Clark group are reviewed. Examples of the implementation of these strategies in the reported syntheses of the F–J fragment of the gambieric acids and the A–E fragment of CTX3C are provided. The second chapter of the thesis concerns the construction of the I–M fragment of CTX3C. The two-directional strategy is implemented over several steps, including alkylation, ringclosing metathesis and diastereoselective allylation. The synthetic route from tri-O-acetal-Dglucal to the I–L tetracycle is described and this section concludes with a future outlook.

The rational design of Transition Metal Substituted Polyoxometalates (TMSPs) structures is one of the biggest challenges of synthetic chemists working in the field. Even though it is known that certain factors such as the pH of the reaction or ratio of starting materials can determine the structure of the most commonly synthesised Polyoxometalates (POMs), total structural control is not yet achieved. This exposes the difficulty of rational TMSP design, which is an extremely important goal towards targeting certain structures with specific properties. In the work presented here, the design of a specific building block, the {PW6} unit, is examined. The connectivity of this moiety allows the introduction of curved features into a structure. Herein, different cobalt containing structures which possess the Keggin type {PW6} fragment in their framework are reported. These structures were synthesised using {P2W15} as a building block, and such a Dawson to Keggin transformation is unprecedented. Water oxidation catalysis is of extreme importance, as it is an energetically demanding step in the water splitting process, where hydrogen as a clean fuel can be obtained. Most Water Oxidation Catalysts (WOCs) still use precious metals. However, a few earth-abundant TMSPs-WOCs exist. The most used strategies when it comes to optimising these catalysts are based on changing the heteroatom, the transition metal or the whole structure itself. It was decided to investigate whether the tungsten framework of a given catalyst could be modified by doping with molybdenum. It was found that different amounts of molybdenum could be doped into the tungsten framework of the structure, and the process also gave rise to two types of crystal for each molybdenum to tungsten ratio. These two crystal types were due to cationic differences alone. During electrochemical analysis of these compounds it was decided to investigate the effect of two different experimental setups to determine not only if the composition of the catalyst contributed to the overall behaviour, but also if the nature of the working electrode had a significant effect. Both methods demonstrated that the molybdenum doped materials synthesised in this work were WOCs and were more efficient than the tungsten parent. The reason for investigating the setup is that in the literature no two electrochemical setups of TMSPs WOCs are consistent, which is worth exploring. It was found that the setup did have a significant effect as when carbon paste electrodes (CPEs) were used the compound with less molybdenum content had the best water oxidation catalysis properties. Whereas with the Nafion ink preparation the inverse was true. This calls into question how accurately different WOCs tested on different setups can be compared.

In the production of ethylene and propylene via steam cracking, one of the major by-products is pygas. This mixture has a high octane number, owing to the large quantity of aromatics, diolefins, and olefins present within this mixture. This stream contains, in particular, a significant quantity of benzene and toluene. This is a waste product, but is currently heavily utilised for the extraction of benzene, mainly in order to produce styrene, cumene, and cyclohexane. While the demand for these compounds will continue to increase, the usage of pygas products will decrease in terms of its other main use, as a petrol additive, due to the increasingly strict regulation regarding the total allowable content of aromatics in fuel. When attempting to refine pygas for use as an aromatic chemical feedstock, the most common method of purification is to perform a hydrocracking reaction. Reactions will usually be carried out in two steps; the first is to hydrogenate the diolefins and styrene over, typically, a Pd-alumina catalyst under mild conditions. The second stage involves hydrogenating olefins, removing sulfur compounds by converting them into H2S, acid-catalysed ring opening of napthenics, and cracking paraffins. The aim of this research was to perform an analysis of the effect of reaction mixture on the retention of benzene when passed over an industrially-used bifunctional metal/zeolite hydrocracking catalyst, and to analyse the carbon laydown and other relevant effects produced by altering the reaction mixture. Previous work looking at pygas has mostly been carried out using only one, or a few, reaction compounds for simplicity of analysis. A number of studies use only styrene as a model for pygas. This is an excessively simplistic model of the reaction, and neglects the interactions between the various components of pygas present in a real reaction setting. Therefore, within this research, a mixture of alkanes, cycloalkanes, and aromatics are used to make a model reaction feed. These were reacted over the hydrocracking metal/zeolite catalyst, and an as-prepared zeolite catalyst. This reaction mixture model is more comprehensive in scope than most research performed, without also including olefins, which would accelerate coking of the catalyst, therefore obscuring the more basic interactions between aromatic and saturated paraffin compounds. The efficacy of each reaction mixture was measured by running a model feed based on common pygas compositions in industry, then running reactions in which a single one of four of the the six feed components was removed from the mixture. When the as-prepared zeolite support was used as a catalyst it was found to crack more of the aromatics, benzene and toluene, along with producing significantly more xylenes due to disproportionation, than the metal/zeolite catalyst. One of the main causes of catalyst deactivation in hydrocracking catalysts is coking, due to carbon deposition. The effect of coking was analysed using thermogravimetric analysis (TGA) ex-situ, which was also verified using CHN analysis. The as-prepared zeolite support was found to produce more carbon laydown than the metal/zeolite catalyst, although it is unclear if the difference would have a significant effect during longer reactions. Within the two groups of catalyst, metal/zeolite and zeolite, the total quantity of coke detected for each reaction mixture was found to show some variation, but would be similar. Some of the reaction mixtures showed a difference in product composition in the offline GC results, although the cause of this is unclear. The results in these reactions cannot, therefore, be anticipated based upon a simple addition-subtraction model in terms of feed components, as there appears to be a complex interdependence between these components that influences the final retention of products observed, that was not assumed to be present before this work was carried out. Analysis of the coke deposit by Raman spectroscopy revealed that the graphite platelets in all reactions were between 10 and 13 nm. Therefore, it appears coke deposition was observed only on the external surface of the catalyst.

The spliceosome is the cellular machinery involved in producing mature messenger RNA from pre-mRNA before it is translated into protein by the cells. Improved understanding of this vital cellular process would allow us to design better drugs to combat diseases that depend on splicing mismanagement. Small molecules that affect splicing would be useful in furthering our understanding of this complex cellular mechanism. Hinokiflavone, a biflavonoid natural product, was found to affect splicing in cells. In this work we describe the total synthesis of hinokiflavone, after exploring alternative synthetic routes. Several different series of hinokiflavone analogues were also designed and three of these structural analogues displayed the same bioactivity as hinokiflavone. Various biological assays in which hinokiflavone and the analogues were active were then examined. It was found that these molecules modulate splicing by inhibiting SENP activity. The SENP enzyme removes SUMO, a post-translational modification involved in the cellular control over splicing, hence its inhibition has a marked effect on cellular metabolism.

The aim of this thesis is to describe the rapid microwave synthesis of a number of transition metal carbides and nitrides as well as their structural characterization and develop reproducible procedures that can cut processing times and, hence, reduce the energy consumption. Specifically, 4 binary systems are investigated: V–C, Zr–C, Hf–C and Zr–N. Carbide syntheses were conducted using either elemental or oxide precursors under argon, whereas the nitride system was investigated from zirconium powder under either nitrogen or ammonia gas. Microwave syntheses were conducted using both multi-mode cavity (MMC) and single- mode cavity (SMC) microwave reactors at a power of 800 W and 1 kW, respectively, with an operating microwave frequency of 2.45 GHz. Vanadium carbide production from both oxide and elemental precursors was achieved in 6 minutes for MMC experiments and 2 minutes for SMC experiments. Zirconium carbide was obtained from zirconium powder and graphite in 20 minutes in a MMC reactor and 6 minutes in a SMC reactor. Unfortunately, the carbothermal reduction of ZrO2 to ZrC was not successful as the starting materials did not react with each other and no product formation was observed. Similar results were obtained for the carburization of HfO2. However, hafnium carbide was synthesized combining graphite with hafnium metal in 20 minutes in a MMC reactor and 6 minutes in a SMC reactor but the formation of additional oxide phases (i.e. HfO2) was also observed. Finally, zirconium nitride production was investigated in a MMC reactor and prepared in 20 minutes from zirconium metal under either N2 or NH3 gas. Generally, oxygen inclusion was observed in all experiments either in the form of oxycarbide or additional oxide phase(s). Once a reproducible experimental technique was established, products were characterized by several analytical techniques. Powder X-ray diffraction (PXRD) was used to identify product phases, study the phase evolution of the microwave processes and refine the MW-synthesized structures by Rietveld method. Powder neutron diffraction (PND) was used on the V-C and Zr-C samples to evaluate product purity and the C and O occupancies of the final products. Scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX) provided information about product morphology, particle size and purity. EDX supported the evidence for oxygen inclusion across samples. Supporting information in favour of this was additionally offered by Raman spectroscopy. X-ray photoelectron spectroscopy (XPS) was used to analyze the surface of products together with the chemical state of the elements present in it.

This thesis describes the development of a mild, one-pot, diazotisation-iodination reaction, via a stable diazonium salt intermediate. The reaction is tolerant of various functional groups and substitution patterns, and was used as the final step in the synthesis of six potential or currently used radiotracers for SPECT imaging. The transformation was also adapted for use with sodium [125I]iodide as a mild, operationally simple method to access 125I-labelled SPECT radiotracers. The full radiosynthesis of the imaging agent iomazenil is described with iodine-125 and iodine-123. This one-pot reaction was then utilised for the development of new SPECT imaging agents for the N-methyl-D-aspartate (NMDA) receptor. A small library of analogues based on the SPECT imaging agent CNS1261 were synthesised. The final project describes the development of a metal-catalysed iodination reaction from non-halide starting materials. The use of a highly active ruthenium catalyst and a nonaflate leaving group gave promising results for a number of substrates.

The object of this thesis, is to demonstrate the potential capabilities of injection moulded chiral plasmonic nanostructures for enhanced sensing in biological systems. The key phenomenon employed throughout this thesis is the generation of electromagnetic fields, that produce a greater chiral asymmetry than that of circularly polarised light, termed ‘superchiral’ fields. These superchiral fields will be demonstrated as being an incisive probe into the structure, conformation, and orientation of proteins immobilised on the nanostructure surface of these injection moulded substrates. Initially, it will be shown how this phenomenon is sensitive to higher order changes in protein structure induced upon ligand binding, using an asymmetry parameter extracted from the optical rotatory dispersion (ORD) spectra. Where these changes would not be routinely detected by conventional chiroptical spectroscopy techniques, such as circular dichroism (CD). Further to this, as these nanostructures display the plasmonic analogue of the interference effect, electromagnetically induced transparency (EIT), a narrow transparency window is created within a broad reflectance spectrum. Where the spectra can be modelled using a simple coupled oscillator model, and the retardation phase effects extracted. This allows two new asymmetry parameters to be introduced for characterising any changes induced by the biological samples, the experimental separation parameter ∆∆S, and the modelled retardation phase asymmetries. These will be used to characterise the orientation of three structurally similar protein fragments, called Affimers, with the modelled phase asymmetries being shown as a particularly incisive probe into the surface immobilised orientation. Furthermore, conformational changes in the cancer relevant protein, HSP90, will be characterised upon the addition of increasing concentrations of the inhibitor molecule 17-AAG. With the orientation of the immobilised HSP90 protein being shown to influence the sensitivity observed for any protein-ligand interactions that occur. Finally, this phenomenon will be used to quantitatively detect elevated protein levels in a complex solution. Elevated levels of IgG will be measured in human blood serum solutions, utilising the isoelectric point of the proteins in solution to enhance the level of IgG adsorbed in the protein corona. This will demonstrate for the first time, the use of superchiral fields generated around injection moulded chiral nanostructures, to detect protein changes in complex real life solutions, such as human blood serum. Representing the first step in creating a high-throughput ultrasensitive system for a range of diagnostic applications.

Ajudazol B is a polyketide secondary metabolite, isolated from Chondromyces crocatus in 2002, that exhibits anti-fungal activity through potent inhibition of the electron transport chain. The main objective of the work described in this thesis was to use and expand the oxidative rearrangement of isobenzofurans to generate isochromanones, and apply this towards the total synthesis of ajudazol B. The rearrangement was used as a key step in the synthesis of the full ajudazol B framework. The synthesis was achieved in 20 steps and 11% overall yield. The isomer of ajudazol B was synthesised in 21 steps and 8% overall yield. Its biological activity remains to be determined.

Porous Lewis acids are rapidly emerging heterogeneous catalysts, particularly for the upgrading of biorenewable feedstocks, due to their ability to coordinate lone-electron pairs from oxygen atom, hence inducing molecular rearrangements and cleavage. As such, this study tackles one of the most important challenges in liquid phase catalytic chemistry, namely the design of novel Lewis acidic zeolites to act as heterogeneous catalysts for liquid phase applications. Lewis acidic (Sn-BEA) zeolites are typically synthesised by highly complicated hydrothermal synthesis procedures, which have significant downsides preventing industrial application. In addition to technical difficulties, some drawbacks minimize the effectiveness of Sn-BEA in industrial interest. Amongst these limitations are 1) long crystallization time (40 days), 2) the large crystallite sizes obtained via typical hydrothermal synthesis, resulting in mass-transfer issues, and 3) the low Sn amount (typically < 2 wt.%), resulting in low space-time yield. Furthermore, a relatively amount of undesirable HF is required to induce crystallisation. Therefore, much academic and industrial research is currently devoted to the development of new methodologies for preparing Lewis-acid zeolite catalysts with higher or similar activity. The broad context at this doctoral dissertation is to investigate the potential of acid leaching (i.e., demetallation) of commercial (Al-containing) BEA zeolite as a simple, versatile, and scalable method to introduce different amounts of active centers (Sn) in zeolites, using solid-state incorporation (SSI). To evaluate the activity of the synthesized catalysts, the study focused firstly on the Meerwein-Ponndorf-Verley (MPV) transfer hydrogenation of carbonyl compounds and isomerization of glucose. Owing to the low activity of Sn-BEA micropores catalyst for the activation of bulky molecules, mesopores are subsequently created via top-down alkaline treatment to synthesis hierarchical Lewis-acid porous zeolite (Sn-h*-BEA), by employing the post-synthetic demetallation route. This catalyst, was evaluated in reactions that involve bulky molecules, such as cyclooctanone (C8) and cyclododecanone (C12). Sn-h*-BEA was found to be active, selective and more stable for continuous operation than its purely microporous analogue. Subsequent work focused on the catalytic valorisation of bio-renewable feedstock, which often relies upon multi-stage processing of highly-functionalised substrates, resulting in selectivity and process engineering challengers. Later parts of this thesis therefore report the synthesis of a novel acid-base bifunctional catalyst [Sn-Al] BEA which contains Sn-related Lewis acid sites and Al-related BrØnsted acid sites. This bifunctional catalyst has been tested, as a catalyst for the cascade catalytic transfer hydrogenation and etherification of furfural, under batch as well as continuous flow reaction condition. With this catalyst, furfural was first converted by Lewis acid Sn(Ⅳ) framework sites to form furfural alcohol via transfer hydrogenation from the solvent. Subsequently, furfuryl alcohol etherification with the solvent is catalysed by the BrØnsted acid (Al) framework to produce corresponding alkyl furfuryl ether. Such ethers are highly desirable as bio renewable fuel additives.

The photocatalytic degradation of cinnamic acid, by TiO2, has been studied extensively in aerobic and anaerobic conditions and in the presence of common salts often found in industrial waste waters. Analysis of the intermediates formed found that molecular oxygen is central to forming the important radicals for the main benzaldehyde mechanism by which cinnamic acid initially degrades, as well as a key component required for the mineralisation to carbon dioxide. In the absence of molecular oxygen an alternate, but slower, pathway becomes the prevalent. The hydroxyl driven mechanism is capable of decarboxylation of the initial carboxyl group but further oxidation does not occur at a reasonable rate. By investigating the effect of salts in solution we found that sulfates and chlorides both interfere with degradation mechanisms and decrease the mineralisation efficiency of titania photocatalysis. Sulfates blocked important surface sites needed for substrate binding that inhibited the benzaldehyde pathway and slowed down the degradation pathway. Whilst chloride formed radical chlorine species (Cl∙) in the presence of TiO2 that resulted in the increase of cinnamic acid removal and the emergence of new reaction pathways. Cl∙ competed with the superoxide radical anion (O2∙-) to attack across the double bond of cinnamic acid, decarboxylate and form several new acetophenone-derived intermediates. A widening of the intermediate map, through the formation of new intermediates, is coupled with a significant slowing of total mineralisation which presents real issues for photocatalytic waste water treatment where chloride ions are present. Additionally, the chlorine radical induced pathways produce intermediates of a greater toxicity; bringing the implication that partial oxidative degradation could result in waste water with an increased toxicity. Anodic nanotubes were explored as an option for alternative materials to be used within photocatalytic reactors. Nanotubes anodised for 8 hours were found to be the most photoactive in the liquid phase, and in the surface degradation of contaminants, due to the wider pores that were structurally sound enough to not slope and reduce light penetration. The surface topography was identified as the key factor for promoting photocatalysis. It was also found that the materials had a cross-phase applicability, in that the most active liquid phase nanotubes were also the most efficient for surface degradation. The incorporation of tungsten into the anodisation process did not improve the photocatalytic activity. Photodeposition of palladium and gold resulted in a decrease in the degradative efficiency of the nanotube arrays. Pd/TiO2 and Au/TiO2 powders were found to reduce the degradation rate of cinnamic acid in oxygenated conditions, although both metals improved the oxidation of surface deposits of carbon. In deoxygenated conditions, Pd/TiO2 catalysts exhibited superior degradation of cinnamic acid in comparison to plain TiO2 and gold doped catalysts. Enhancements in the mineralisation rates, to CO2, were also found. The improvements were attributed to the presence of palladium improving charge separation and introducing new reaction sites capable of decarboxylating the alcohol and aldehyde functionalities, respectively. While the gold nanoparticles were poorly dispersed, they were found to increase the selectivity for phenylacetaldehyde, in deoxygenated conditions, by a factor of 5.