The stereoselective construction of fused 5,7-bicycles has attracted considerable attention due to the ubiquity of this motif in complex biologically active sesquiterpene lactones (dehydrocostus lactone, helenalin). Transition metal-catalysed carbocyclisation reactions represent a highly attractive approach towards the construction of functionalised cyclic and polycyclic molecules. Generation of 5- and 7-membered rings from strained 3-membered cycles has emerged as a particularly effective strategy, which is complementing more traditional pericyclic reactions. The description of the transition metal-catalysed carbocyclisation reactions of alkylidenecyclopropanes (ACPs) is provided in the introductory review, which seeks to highlight the evolution of these processes and their application in the context of the construction of 7-membered rings. Despite the numerous advantages that are afforded by this approach, the methods, that allow the synthesis of the suitably functionalised carbocycles for the synthesis of complex natural products, are still rare. Chapter 2 describes our work on the cycloaddition reactions of functionalised olefins, which resulted in the development of highly regio- and diastereoselective rhodium-catalysed [(3+2)+2] carbocyclisation of vinyl silanes with various monosubstituted alkynes. The transformation provides silylated cis-fused 5,7-bicyclic systems, which can be further modified in a number of ways. We have demonstrated that selective oxidation of the silyl group affords C6 hydroxylated 5,7-bicycles – a motif reminiscent of guaianolide and pseudoguaianolide natural products. We anticipate that the methodology outlined herein will find significant application in target directed synthesis. Chapter 3 provides an account of our synthetic efforts towards guaianolide (+)-repin. Rhodium-catalysed [(3+2)+2] carbocyclisation was successfully employed for the construction of the cis-fused 5,7-bicyclic system at the core of the molecule. In the course of these studies we developed an effective strategy for the functionalisation of the 7-membered ring through a series of oxidative transformations. The lactone moiety was introduced via substrate-controlled radical reaction of bromohydrin with silyl ketene acetal and constitutes the first application of these reaction conditions to bromohydrins for the direct synthesis of lactones. We believe that our strategy towards the tricyclic core of repin could also find application in related natural products, providing a general entry to the guaianolide family of compounds.

The work of this thesis focuses on three perovskite-based compounds: YSr2Cu3−xCoxO7+δ cuprates, Gd2BaCo2O5+δ related phases and Sr2SnO4 Ruddlesden-Popper structures. Both YSr2Cu3−xCoxO7+δ and Gd2BaCo2O5+δ are cathode material candidates for solid oxide fuel cells (SOFCs). Doping of Sr2SnO4 aims to enhance the ionic conductivity of the parent phase and explore the phases as a potential SOFCs electrolyte material. The cobalt content in the layered perovskite YSr2Cu3−xCoxO7+δ has been increased to a maximum of x = 1.3. A slight excess of strontium was required for phase purity in these phases, yielding the composition Y1−ySr2+yCu3−xCoxO7+δ (where y = 0.03 and 0.05). The potential of Y1−ySr2+yCu3−xCoxO7+δ (where x = 1 to 1.3) as a cathode material for a solid oxide fuel cell has been explored through optimisation of processing parameters, AC impedance spectroscopy and DC conductivity measurements. The stability of Y0.95Sr2.05Cu1.7Co1.3O7+δ with commercial electrolytes has been tested along with the stability under CO2. This material exhibits a significant improvement in properties compared to the parent member, Y0.97Sr2.03Cu2CoO7+δ, and is compatible with commercially available doped ceria electrolytes at 900 °C. Energetics of Ln2BaCo2O7 (Ln = Gd, Nd, Ce) materials consisting of a layer of LnBaCo2O5+δ (Ln = Gd, Nd) and a fluorite layer (CeO2 or Ln2O3, Ln = Gd, Nd) have been studied using DFT calculations. Various reactions including binary oxides and double perovskites were taken into an account for the formation energy calculations. Phases favourable in DFT calculations were observed also in PXRD patterns of the materials prepared by a solid state synthesis. DFT prediction has been also used in the work with Ruddlesden-Popper phases. The structures of experimentally prepared Nb- and Ta-doped Sr2SnO4 phases were investigated using high resolution diffraction methods. The conductivity of single phased materials was studied by AC impedance spectroscopy. A significant improvement in conductivity was observed in Sr2Sn1−xTaxO4 compounds with x = 0.03 and 0.04. The origin of the enhancement has been studied using different techniques such as solid state Sn-NMR, UV-vis and NIR spectroscopy methods and it tends to be explained by an ionic contribution.

The activation of carbon-hydrogen (C–H) and carbon-carbon (C–C) bonds by transition metal catalysts is an attractive strategy to streamline organic synthesis. Herein this manuscript, the two main areas of research are described. Firstly, it was found that a nickel catalyst can promote the insertion of alkynes into the C–C bond of 3-azetidinones and 3-oxetanones to enable quicker access to pyranones and pyridinones in high yields and excellent regioselectivity. Secondly, a rhodium-catalysed pyridine directed C–H bond activation enables the rearrangement of 1,6-heptadienes into bicyclo[2.2.1]heptanes in good yields. Importantly, three stereogenic centres are created with complete diastereocontrol in this atom-efficient reaction. In chapter 1, an overview of the literature on transition metal-catalysed C–C bond activation of four membered rings is described. In chapter 2, our efforts to optimise the catalytic conditions and build the scope of the nickel-catalysed reaction are reported. In chapter 3, the results of the mechanistic investigations of the nickel-catalysed reaction are reported. Finally in chapter 4, a brief overview of the transition metal-catalysed functionalisation of an alkene C–H bond with another alkene is described. Subsequently, the optimisation of the catalytic conditions and the scope of the diastereoselective carbocyclisation of 1,6-heptadienes triggered by rhodium-catalysed activation of an alkene C–H bond are reported.

Thin film components for solid oxide fuel cells (SOFCs) have been investigated in this thesis. This work focuses on electrolyte materials such as samarium doped ceria (SDC) and cathode materials including neodymium barium cobalt oxide (NBCO) and barium calcium yttrium iron oxide. Single layer growth of NBCO or SDC is achieved on single crystal strontium titanate (001) before these materials were grown via pulsed laser deposition as a bi-layer and multilayers. Ordered NBCO required deposition at 850°C, whereas it was found that the SDC grew with a lower surface roughness at lower temperatures of around 650°C. The motivation was to investigate how the conductivity is affected by the interfaces between these layers, as motivated by previous studies of yttrium stabilised zirconia (YSZ) with strontium titanate (STO). NBCO was found to be unstable at the temperatures required for AC impedance measurements. From the transmission electron microscopy (TEM) and Energy Dispersive X-ray (EDX) data there is likely migration of Nd into the SDC layers. The interfaces are also less sharp for the multilayer films deposited at the higher temperature for the SDC growth. However, in all cases the SDC growth appears more favourable in the TEM when compared to the NBCO, with some regions even showing Co-metal and fluorite structures potentially attributed to Co-Ox where we would expect to see the perovskite block. Thin films of barium calcium yttrium iron oxide were grown on single crystal strontium titanate (001). The material is a candidate cathode for solid oxide fuel cells (SOFCs) and in the intermediate temperature (IT) region at 600°C the in-plane AC conductivity of the thin film is found to be 30.0Scm-1, significantly enhanced over 3.5Scm-1 found for the polycrystalline form. This is assigned to reduction of the grain boundary density and alignment of the planes predicted to have the highest electronic and ionic conductivities. The symmetry of the film appears to be tetragonal within the resolution of the measurements employed, as opposed to the orthorhombic symmetry of the bulk phase, which may be attributed to the in-plane structural match between the cubic STO substrate and the grown layer. Three potential geometries investigating both single and double-sided growth for measuring the area specific resistance of thin films are discussed and an experimental prototype constructed and tested.

Chronic pain is a global medical-health problem. It is estimated that approximately 20% of the adult population suffer from some form of chronic pain. Along with the physical and emotional burden that living with chronic pain brings to the individual, there is also a huge socio-economic cost implication currently estimated at more than €200 million per annum in Europe and at over $150 million in the USA. Unfortunately, because of a lack of efficacious treatments, chronic pain is poorly managed. Current therapies for chronic pain act upon well-established targets and have been shown not only to be inadequate for the majority of patients, with only 1 in 4 patients only finding up to 50% relief from their painful syndromes There is, therefore, a continued need for novel analgesic drugs that act at novel therapeutic targets. With the elucidation of the role of α1 glycine receptor (α1 GlyR) plays in nociceptive pathways it has become an attractive target for novel analgesic compounds. Previous work with the group has identified a series of potent bi-phenyl compounds targeting the α1 GlyR with EC50 values in the low nM range. However, these compounds suffered from poor physicochemical and pharmacokinetic properties. Work in this thesis describes the rational design and synthesis of a library of compounds which selectively target the α1 GlyR with EC50 values in the sub nano-molar range. We have successfully progressed from hit to lead stage with improved efficacy and DMPK properties. The lead compound has shown excellent PK profiles, CNS penetration properties and no toxicity issues. We have obtained proof-of concept for the lead compound in a rat model of neuropathic pain and are currently moving forward with lead optimisation.

The work presented in this thesis focuses on the effect on structure and properties of the rhombohedral (R) perovskite system, Bi(Ti3/8Fe2/8Mg3/8)O3 (BTFM), when solid solutions with CaTiO3 (CTO) are made. Bismuth-based perovskites are established as candidates to replace the piezoelectric material Pb(Zr1-xTix)O3 as they have high Curie and depolarisation temperatures which are necessary for applications and are not toxic. BTFM has a Curie temperature of ~730 °C; however it shows poor electromechanical properties. In Chapter 3 of this thesis is shown that a range of xBTFM-(1-x)CTO compositions were synthesised successfully in the range 0.6 ≤ x ≤ 1 obtaining the perovskite structure. They were proved to be polar by second harmonic generation measurements. Compositions in the range 0.6 ≤ x ≤ 0.825 adopt an orthorhombic (O) structure. For x ≥ 0.95 the R structure crystallises in the polar space group R3c with polarisation along [111]p as BTFM while in the range 0.837 ≤ x ≤ 0.925 a mixed phase, O + R, region is achieved. In Chapter 4 of this thesis, the study of the space group assignment for the O phase based on the reflection conditions and microscopy studies is shown. By using the Maximum Entrophy Method / Rietveld method a six sites disordered model for the A-site has been built based on the charge density distribution using synchrotron X-ray diffraction (SXRD) data. A joint refinement using SXRD and neutron data was performed on composition x = 0.8 and the structure of this new polar phase crystallising in Pna21 with polarisation along [001]p has been solved. However, the O phase despite of being polar displays poor physical properties being the maximum piezoelectric coefficient obtained of 2.8 pC/N for x = 0.835 . In Chapter 5, preliminary structural analysis outcomes for the mixed phase, O + R, compositions with different polarisation directions along [001]p and [111]p respectively are shown along with their physical properties measurements results. By making solid solutions of BTFM and CTO, a maximum piezoelectric coefficient of 53 pC/N has been achieved for x = 0.835. This value is about two orders of magnitude greater than for BTFM (0.6 pC/N). A preliminary phase diagram of xBTFM-(1-x)CTO materials versus temperature has been built.

Reactions involving nitrogen transfer are of great industrial interest. Utilizing nitrides in this manner, in principle, could help industries overcome the increasing challenges which they face to meet economic and environmental targets. An example of this is the possible application of metal nitrides in the direct synthesis of aniline from benzene, which could potentially remove the need for the lengthy, uneconomical, and environmentally unfriendly process which is currently employed. In the work presented in this thesis a screening study has been undertaken which explores the reactivity of lattice nitrogen within bulk and supported transition metal nitride catalysts. The experimental work has been conducted with the aim of developing a potential nitrogen transfer reagent in order to synthesise aniline via the direct conversion of benzene and has focused on three main objectives: determining the most active transition metal nitride catalyst for ammonia synthesis, in the absence of N2 to determine the reactivity of “lattice” nitrogen. It was necessary at this point to establish which materials were reactive and lost nitrogen from the metal lattice at or below 400oC, the maximum temperature for the envisaged process. Materials which demonstrated a subsequent loss of lattice nitrogen upon reaction with H2/Ar were then screened to establish whether it was possible to restore the original nitrogen content in the materials in order for the nitrides to function in a Mars-van Krevelen type capacity. Finally the reaction of benzene and hydrogen over bulk binary nitrides was conducted in an attempt to trap reactive NHx species for the production of aniline. It was found that no aniline was produced in these reactions. However, some interesting results were obtained over a selection of nitride materials, namely Co3Mo3N, Cu3N, Zn3N2, Re3N and a metallic Co-4Re compound where low quantities of, as yet unidentified, reaction products were formed. To the author’s knowledge, this is the largest systematic study of bulk nitrides and related materials which has been investigated on this scale and which has been directed towards this specific, novel, target process.

The catalytic hydrogenation of substituted benzenes to saturated cyclic products is an industrially relevant reaction. It is important in the production of fine chemicals, petroleum and in the fuel industry. It is used in the process of lowering the aromatic content in diesel fuels to follow up the up-to-date environmental legalisation. It has been widely reported that aromatic ring hydrogenation is a structure insensitive reaction, however more recent studies have suggested that structure sensitivity may indeed exist. Therefore, the demand to perform more research on substituted benzenes to understand their behaviour during the hydrogenation has increased. Unlike most of what was found in literature, this study involved substituents which include methyl, ethyl, propyl, hydroxyl and methoxy groups. These reactions were performed at different parameters of temperatures, H2 pressure and concentrations and over Rh/SiO2 catalyst. Different mechanisms were suggested for the hydrogenation of aromatic compounds. A stepwise mechanism is generally accepted to explain the reaction mechanism. This suggestion was built on the fact aromatic adsorption is zero order in aromatics which suggests a strong adsorption of the substrates. This mechanism was confirmed in this work by the observation of alkyl cyclohexenes as intermediates during the hydrogenation of alkyl benzenes. Interesting points were observed during the hydrogenation of phenols. Firstly, cyclohexane was formed independently and directly from the original phenol. This observation was not found in most of previous studies. The other point was that phenol and anisole reacted in different ways from each other. Phenol was found to react in three independent routes, the formation of cyclohexanone, the formation of cyclohexanol and the formation of cyclohexane. Whereas, cyclohexanol was not formed directly from anisole, it was formed from cyclohexanone and after the total conversion of anisole. Competitive hydrogenations were also executed in order to investigate the behaviour of different groups in the same reaction. The findings of these tests were different from what was observed during the solo tests. As for the hydrogenation of alkylbenzenes, a steric effect might explain the differences between these substrates. It was observed that the reaction rate decreased as the alkyl group attached to the ring increased. These findings were not the same during the competitive hydrogenation. n-Propylbenzene, which has a larger group attached to the aromatic ring, showed higher reactivity in the presence of toluene and ethylbenzene, which suggests that the steric effect was not the only factor affecting the hydrogenation of substituted benzenes. These findings were explained by an electronic effect applied by the alkyl groups attached to the ring. The effect of these groups increases as the group size increases. In addition to steric and electronic effects, the mode of adsorption was also suggested to affect the competitive hydrogenations of phenols. Different modes of adsorption and different medium species formed leads to different behaviour during the competitive hydrogenation. In addition, NMR analysis was performed on selected samples from toluene and deuterated toluene reactions with deuterium and hydrogen. Toluene reaction with deuterium showed that all hydrogen atoms were replaced by deuterium at the beginning of the reaction. It was also shown from NMR results that -CD3 group was contacted to the surface which confirms the ability of -CH3 group to be adsorbed to the surface as well as the aromatic ring.

Due to their extensive and important medicinal properties, the indole alkaloids are an important class of natural products. A key step towards the total synthesis of indole alkaloids is the diastereoselective Pictet-Spengler reaction, which has enabled the total syntheses of a number of these natural products to be reported, one of which is the medicinally-important alkaloid ajmaline. Ajmaline is well studied and the previous attempts towards its synthetic preparation are described. During our investigations towards the asymmetric syntheses of ajmaline and other related indole alkaloids, it was found that the kinetically-controlled Pictet-Spengler cyclisations of L-tryptophan allyl ester gave cis-3,5-disubstituted tetrahydro-β- carbolines with enhanced stereoselectivities of up to 20:1. The Pictet-Spengler reaction of L-tryptophanamide was also studied and the cis/trans tetrahydro-β- carbolines were formed in a ratio of 3:1, typical of that for other ineticallycontrolled Pictet-Spengler cyclisations reported previously. Studies towards our total synthesis of ajmaline are also described. The synthesis features the kinetically-controlled Pictet-Spengler reaction, a highly stereoselective intramolecular Michael cyclisation and a one-pot indole cyclisation/reduction procedure, which was used to introduce three stereocentres simultaneously. It was found that the nitrogen protecting group has a defining role to play in both the indole cyclisation step, and during reduction of the subsequent iminium ion through remote steric induction. Despite installing seven of the nine stereocentres with high levels of stereocontrol, an inability to remove the robust nitrogen amide protecting group prevented completion of a total synthesis. The final ring-closing protocol could be carried out using semi-synthetic material derived from ajmaline. Cyclisation was achieved by the selective oxidation of a primary alcohol to the aldehyde, which spontaneously ring closed under the conditions of the reaction to complete the ajmaline framework.

Alumina supported nickel and gold-doped nickel catalysts have been investigated for their use as hydrocarbon steam reforming catalysts. The influence of calcination temperature during preparation has been investigated using a variety of techniques including X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), BET surface area analysis, scanning electron microscopy (SEM) and temperature-programmed reduction (TPR). It has been shown that the nickel phases present and their subsequent reducibility are strongly dependent upon the calcination temperature during preparation. As the calcination temperature is increased nickel aluminate (NiAl2O4) is formed and nickel oxide–support interactions increase. The addition of gold to the catalyst increases nickel oxide–support interactions, lowering the sample reducibility and increasing formation of NiAl2O4 at lower calcination temperatures. The calcination temperature significantly influences the steam methane reforming characteristics under both stoichiometric and methane-rich reaction conditions and the presence of unreduced NiAl2O4 significantly alters catalytic activity. Under the reaction conditions employed, the presence of gold provides no long-term benefit towards catalyst performance, resulting in a reduced reforming activity, especially at lower reaction temperatures, and in certain cases an increase in carbon laydown. Sulfur addition to the reaction mixture results in catalyst poisoning and in some cases complete deactivation, particularly at low reaction temperatures. However, sulfur addition does significantly increase resistance to carbon deposition. The addition of sulfur to the reaction mixtures and gold-doping of catalysts provides an increase in carbon resistance, whilst significantly reducing the rate of sulfur poisoning and increasing catalyst lifetime. This research discusses the influence of calcination temperature on steam methane reforming activity, catalyst resistance towards carbon formation and sulfur tolerance under variable reforming conditions over alumina supported nickel and gold-doped alumina supported nickel catalysts.