Stereotactic neurosurgical robots allow quick, accurate location of small targets within the brain, relying on accurate registration of preoperative MRI/CT images with patient and robot coordinate systems. Fiducial markers or a stereotactic frame are used as registration landmarks and the patient’s head is fixed in position. An image-based system could be quick, non-invasive and allow the head to be moved during surgery giving greater ease of access. Submillimetre surgical precision at the target point is required. An octant representation is utilized to investigate full region of interest (ROI) head registration using parts only, with registration performed using the Iterative Closest Point (ICP) algorithm. Use of two octants sequentially obtained a mean RMS distance of 0.813±0.026 mm; adding subsequent octants did not significantly improve performance. An RMS distance of 0.812±0.025 mm was obtained for three octants used simultaneously. ICP was compared with Coherent Point Drift, and 3D Normal Distribution Transform, with and without added or smoothed noise, and was least affected by starting position or noise added; a mean accuracy of 0.884±0.050 mm across ten noise levels and four starting positions was achieved, which was shown to translate to submillimetre accuracy at points within the head.

Bioluminescence imaging (BLI) is widely used in pre-clinical research to monitor the location and migration of different cell types, and the growth of cancerous tumours and response to treatments within murine models. However, the quantitative accuracy of the technique is limited. The position of the animal is known to affect the measured bioluminescence, with a change in position causing a change in measurement. Work presented here will address this problem, validating a free space model in a murine model to produce surface bioluminescence measurements which are independent of the position of the animal. The position of the source within the animal and the underlying tissue attenuation also affect the quantitative accuracy of bioluminescence measurements. An extension to bioluminescence imaging, bioluminescence tomography (BLT), aims to overcome these problems by recovering the three-dimensional bioluminescent source distribution within the animal. However, there are limitations to the quantitative accuracy of BLT. Current reconstruction algorithms ignore the bandwidth of band-pass filters used for multi-spectral data collection for BLT. This work develops a model which accounts for filter bandwidth in the BLT reconstruction, improving the quantitative accuracy of the technique. An additional limitation to the quantitative accuracy of BLT is that accurate knowledge of the optical properties of the animal are required but are difficult to acquire. Work to improve the quantitative accuracy by obtaining subject-specific optical properties via a spectral derivative reconstruction method for diffuse optical tomography (DOT) is presented. The initial results are promising for the application of the method in vivo.

This thesis presents DNA binding studies and our work to develop a double competition dialysis assay. Chapter 1 describes DNA structure, including duplex, triplex and quadruplex structures, and functioning in storing the genetic code. This Chapter also presents an overview of the interactions of small molecules with nucleic acids structures. Moreover, the chapter describes the techniques that have been used for our DNA-binding studies, viz, UV - visible spectroscopy, circular dichroism spectroscopy and isothermal titration calorimetry. The chapter also describes potential applictions of small molecule DNA binders. Finally, we describe the competition dialysis in this chapter. Chapter 2 describes the determination of extinction coefficients for selected optoelectronically active π-conjugated molecules in aqueous buffers. Furthermore, we established the light sensitivity of the compounds. In addition, the chapter describes the binding studies of nucleic acid binders from a library of available ligands using UV-visible, circular dichroism, and isothermal titration calorimetry. Chapter 3 describes the development of a custom competition dialysis device. We test this device to determine affinity and selectivity of ligands for nucleic acids structures. We analysed the affinity and selectivity of a single ligand for FS-DNA, specific duplex sequences (dAdT)12●(dAdT)12 and (dGdC)12●(dGdC)12, and different quadruplex structures such as cmyc, 22AG and EAD2. The data agree with the results from UV-vis titrations. In Chapter 4 we explore how double competition dialysis allows screening of two ligands against an array of nucleic acids structures. Several compounds were tested showing that our assay deals reasonably well with fading unless the latter progresses to the extent when absorbance is too low to measure reliably. Although we have identified compounds with promising affinity profiles, even in the presence of a second binder we are yet to identify binders with an orthogonal selectivity profile. In Chapter 5 we present general conclusions and suggestions for future work.

In this work, Density Functional based Tight Binding methods are used according to the Non-Equilibrium Greens Function method, to calculate the thermoelectric properties of phosphorus materials and tin sulfide phases. The effects of several types of phase transitions, on the thermoelectric properties of these layered materials, are considered. It is shown that, not only is consideration of structural and electronic rearrangements within the operating conditions of thermoelectric materials necessary, but that the presence of structural phase transitions, in the absence of an electronic phase transition, may in fact be a powerful means of enhancing the thermoelectric properties of a material.

Energy storage technologies, in particular second-generation rechargeable batteries, are instrumental in addressing the current global demand for clean and sustainable energy. The progress of portable electronics, electric and hybrid-electric vehicles and large-scale grid storage depends on the available technology of rechargeable batteries. Innovation requires a fundamental atomicscale understanding of the properties of the constituent battery materials. Critical to a battery's performance is the electronic and ionic conductivity of the material. Poor ion transport leads to poor rate capability, practical capacity and cyclability. The current research into particle diffusion is predominantly based on single-particle potential energy calculations. Such an approach neglects not only the entropic contribution to diffusion, but the contributions of the collective dynamics which are present in a many particle configuration Using two novel, state-of-the-art enhanced sampling techniques, the 'Shooter' method' and metadynamics, particle diffusion within a many particle system is analysed. The 'Shooter' method is able to connect single particle translocation events into a general particle diffusion mechanism and elucidate diffusion pathways that are otherwise disregarded by single-particle potential energy calculations. This is achieved under consideration of all degrees of freedom, explicitly allowing for local structure changes and lattice dynamics. The application of metadynamics simulations to battery materials is shown for the first time. Using novel collective variables to distinguish between nondiffusive and diffusive regimes, the free energy barrier for diffusion is calculated, therefore considering the entropic contribution. The free energy surface is also reconstructed, highlighting the complex nature of particle diffusion with the olivine phosphates. Using the two novel approaches, the short-time evolution of disorder within the system can be followed and allows for the characterisation of highly complex and correlated translocation events. Additionally,rare events such as twodimensional diffusion and the formation of antisite defects are observed on nominal simulation timeframes. In summary, several novel computational approaches to analysing particle diffusion within battery materials have been developed.

The creation of asymmetric ligands with lower environmental impact is important, as such chiral N,N' ligands attract some attention. A new method for the synthesis of 1,2,4-trisubstituted amino azetidines with \(cis\) relative configuration across its two stereogenic centres was reported in 2013. Due to this \(cis\) conformation, the azetidine compounds are expected to be good chiral ligands for asymmetric catalysis. The nitro aldol (Henry) reaction is an established method for producing new carbon-carbon bonds and is a key reaction in the synthesis of many important compounds. Enantioselective Henry reactions generate carbon-carbon bonds and our azetidines are probed as ligands for that reaction. In this work, new azetidines and their palladium and platinum complexes were prepared and characterised by techniques including X-ray diffraction, confirming retention of the \(cis\) conformation. Furthermore, enantiopure \(cis\)-azetidines were used as chiral ligands for a range of transition metals including the use of Cu-azetidine complexes as catalysts for the Henry reaction, in up to >99.5% ee. New enantiopure amino azetidines and their transition metal complexes are demonstrated as asymmetric catalysts for the asymmetric Henry reaction.

The research presented in this thesis focuses on the process of direct synthesis of hydrogen peroxide from molecular hydrogen and oxygen. This reaction potentially offers an approach which is greener and more sustainable when compared to the current industrial indirect auto-oxidation process. The work presented herein examines some of the key factors in determining the viability of the process in a water solvent at ambient temperature, conditions which would represent a very economically and environmentally attractive option, if feasible. The first part of this thesis investigates the ways in which changing reaction conditions affects the fundamental reaction processes of the direct synthesis reaction – synthesis of hydrogen peroxide and its subsequent degradation by decomposition and hydrogenation. It was found that moving to a water solvent and ambient temperature results in significantly lower yields and greater degradation comparative to previously used water/methanol solvents and 2°C reactions. The second part of this thesis explores the design of catalysts which are active for the direct synthesis of hydrogen peroxide while limiting degradation activity, to increase the yield in water at ambient temperature. A series of supported metal catalysts of the nominal formulation 0.5 wt. % Pd - 4.5 wt. % ‘base metal’ were prepared and treated with a cyclic oxidative-reductive-oxidative heat treatment. This produced highly stable catalysts with activity for the synthesis of hydrogen peroxide, but low to no activity for both decomposition and hydrogenation pathways. These catalysts also fulfilled a secondary aim of producing economically attractive catalysts due to the low loadings of precious metals used. The third and final part of this thesis studies the implementation of these highly selective catalysts in both gas and gas/liquid phase flow reactors. The production of hydrogen peroxide in a gas phase flow system is shown to be attainable although most likely not a commercially viable option. The direct synthesis of hydrogen peroxide in a gas/liquid flow system is shown to proceed with selectivities greater than those previously reported for different catalysts under similar conditions. Tests also show that hydrogen peroxide can be produced under ‘real world’ conditions of high flow rates, a hard water solvent and a dilute hydrogen in air gas mix. These studies could be used to inform future work on high throughput water cleaning technologies.

This thesis manuscript focuses on the synthesis and characterization of branched polyphenylene derivatives in which one or more aryl units are replaced by borazines (B3N3), the isosteric and isoelectronic inorganic analogue of benzene. In particular, the divergent bottom-up synthesis of hexa-branched borazine-doped polyphenylene derivatives is carried out taking advantage of the decarbonylative [4 + 2] Diels-Alder cycloaddition reaction. Given the possibility to graft different functional groups on the aryl substituents at the B and N atoms, borazine-doped polyphenylene frameworks with different doping dosages, topology, and orientations were prepared. The generation of the series of star-shaped borazine-polyphenylene hybrids was possible through the use of borazine-doped or full-carbon core and branching building blocks bearing ethynyl or tetraphenylcyclopentadienone functionalities. Thanks to this synthetic strategy, depending on the chemical nature of the building blocks chosen, it was possible to precisely control the formation of different doping patterns. The photophysical investigation of the synthesized series of hexa-branched BNC hybrid derivatives revealed a progressive reduction of luminescence upon increasing the doping dosage, while the effect of the doping orientation has revealed to be minor. Secondarily, thanks to the Cucatalyzed cycloaddition reaction a suitable chromophore was covalently grafted to a three-branched BNC hybrid polyphenylene scaffold. Photophysical studies assessed the possibility for the borazine-doped polyphenylene backbone to harvest and transfer energy to the chromophore. Finally, the synthesis of borazine-doped graphene sub-structures and large polycyclic aromatic hydrocarbons (PAHs) was envisaged through planarization of suitable borazine-doped polyphenylene derivatives. In this study, the development of a synthetic methodology for the production of these precursors was addressed.

This thesis describes the development and synthesis of a range of novel fluorophores based on 1,8-naphthalimide, N-heterocyclic carbene (NHC) and phosphine derivatives, as well as coordination chemistry with Au(I), Ir(III) and Fe(II). Detailed discussions on the characterisation and the photophysical properties are described, with reference to applications including bioimaging, diagnostics and therapeutics. Chapter 2 describes the synthetic development and spectroscopic analysis of a series of NHC-functionalised 1,8-naphthalimide fluorophores, generating ten new ligands that were successfully utilised for Au(I) coordination chemistry. The optical properties of the compounds were dictated by ligand-centred transitions. Cytotoxicity assessments revealed that compounds were the most toxic to LOVO and MCF-7 cell lines. In addition, lysosomal localisation was observed in cell imaging studies with MCF-7 cells, as seen with structurally related anticancer compounds. Chapter 3 describes the synthetic development and spectroscopic analysis of a series of aminophosphine and phosphinite fluorophores, generating six new ligands, with some successfully utilised for Au(I) coordination chemistry. The photophysical properties were explored in detail due to the presence of different fluorescent groups, including naphthalene, anthracene, pyrene and anthraquinone. In this chapter, 31P NMR was particularly important in confirming the success of the synthetic routes. Chapter 4 describes the comparative syntheses of six new phenyl-1H-pyrazoles and their corresponding cyclometalated iridium(III) complexes using both batch and, successfully applied, flow-microwave methodologies. Isolation of spectroscopically pure species in less than 1 hour of reaction time from IrCl3 was observed, along with ligand-dependent, tuneable green-yellow luminescence. Chapter 5 outlines determination of a successful synthetic route to a series of fluorescent electrochemical biosensors that incorporate both a redox active ferrocene unit and a naphthalimide moiety, with the intention to be applied as an electrochemical detection method for Clostridium Difficile (CDF). Detailed photophysical and electrochemical investigations were used to determine suitability for the desired application.

Increasingly stringent legislation limiting the emissions of particulate matter (commonly referred to as soot particulates) has led to the adoption of particulate filters in the exhausts of both diesel and gasoline passenger vehicles. While filters are highly effective at reducing these emissions, it is necessary to periodically remove trapped particulates in order to avoid their accumulation and the resulting loss of vehicle performance associated with backpressure build-up. An effective method of removing soot particulates is through combustion (oxidation) with the oxygen-containing species present in the atmosphere of the exhaust, however this is unattainable at the temperatures experienced under normal driving conditions. A catalyst able to lower the temperature of soot oxidation is therefore desirable in order to achieve passive regeneration of the filter. Previous studies have identified ceria, CeO2 as a promising soot oxidation catalyst due to its outstanding redox properties, and have shown that it can be enhanced by doping with various other metals. In this work, ceria-based catalysts have been prepared by the co-precipitation method. Ceria was doped with zirconium, lanthanum, praseodymium and neodymium in various ratios in order to enhance its catalytic properties. Each of these materials also contained alumina in order to improve their thermal stability. Of these materials, the most active for soot oxidation was found to be a CeO2-Nd2O3-Al2O3 catalyst prepared in a 7:3:10 molar ratio of Ce:Nd:Al and calcined at 750ºC under flowing air. This catalyst lowered the temperature at which soot oxidation reached its peak rate by over 100ºC. It was also demonstrated that the catalytic activity of these materials benefited considerably from the presence of alkali metals within their structure. The use of the ceria-based materials as supports by impregnating them with other species previously identified as active soot oxidation catalysts was also investigated, which resulted in a further lowering of the soot oxidation temperature. Structural characterisation of the materials was carried out by X-ray powder diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and surface area analysis (BET), while their redox properties were analysed by temperature-programmed reduction (TPR). The catalytic activity of the materials towards soot oxidation was investigated using thermogravimetric analysis (TGA).