This thesis is focused on the study of bimetallic nanoparticles, their structure and evolution as small molecules and reactive species interact with them. Initially we describe Density Functional Theory (DFT), which will be used to find the energies of the nanoparticles and other properties with reasonable computational efficiency. Chapter three focuses on the structural properties of RhPd nanoparticles, including a search of low energy isomers. This is too expensive to be performed at the DFT level, so the Gupta potential was used along with the Birmingham Cluster Genetic Algorithm (BCGA) and Basin Hopping algorithm to conduct the search. Studies were performed on small gold, palladium and gold-palladium bimetallic clusters, with CO adsorption also investigated to see how the structure of the cluster was affected by CO adsorption. This work was then expanded to larger clusters. The 38 atom Truncated Octahedron (TO) was used as a model system to research how CO molecules, atomic hydrogen and atomic oxygen effected the structure of bimetallic nanoparticles. Four separate bimetallic systems were studied: RhPd, PdPt, CuPt and AuPd. The last part of this thesis focuses on AuPt with an emphasis on charge effects and the energy of the d-band.

In this thesis the role of lithium ion conductivity in lithium conducting garnets as potential solid state electrolytes for lithium ion batteries and lithium halide nitrides for solid state hydrogen storage materials is researched. The role of order and disorder on in the lithium sublattice of garnet type materials is investigated. Showing that ordering can cause a change in the unit cell symmetry resulting a tetragonal unit cell. Due to the ordering a drop in the Li ion conductivity is observed. Through a small amount of trivalent doping into the lithium sublattice it is possible to create disorder and hence a change in the unit cell to cubic and an enhancement in the conductivity. For the first time work conducted in this this shows evidence for possible H+/Li+ exchange occurring in air. This exchange was seen to have varying effects on the low temperature lithium ion conductivity. Highlighting the need to take care when preparing and measuring these materials. The structure of a antifluorite type lithium chloride nitride were resolved following inconclusive literature reports. It is shown for the first time that it is possible for these materials to hydrogenate these materials and they have potential as possible solid state hydrogen storage materials. The ionic conductivity of the lithium halide nitrides were measured and compared to that of lithium nitride. And their hydrogen storage properties were related to the ionic conductivity.

The asperparalines belong to a large family of prenylated indole alkaloids possessing a characteristic bicyclo[2.2.2]diazaoctane core structure. More than 70 examples are known to have been isolated from various diverse sources. Chapter 1 discusses the isolation and structure of these compounds along with an introduction to their biosynthesis and biological activities. A combination of unique structural features and intriguing biological profiles has inspired a large body of work regarding the chemical synthesis of this alkaloid family. Chapter 2 gives an overview of the most important strategies for the construction of the central bicyclo[2.2.2]diazaoctane and presents these in the context of several total syntheses. Chapter 3 details an approach to the bicyclo[2.2.2]diazaoctane core using a free radical cascade comprised of a 1,6-hydrogen atom translocation followed by 6-exo-trig and 5-exotrig cyclisations. An initial model system is presented consisting of a series of DKPs synthesised from a propargylated proline derived from a modification of Seebach’s procedure for the self-reproduction of chirality. Addition of a sulfur radical to the acetylene triggers the desired reaction in good to excellent yield and favours the asperparaline stereochemistry. In Chapter 4 the application of this strategy to the synthesis of an advanced asperparaline core structure is presented. While construction of the key cyclisation intermediate proved difficult, the radical cascade proceeds in modest yield to furnish a bicyclo[2.2.2]diazaoctane possessing the key structural features of the asperparalines.

The work described in this thesis concerns the design, synthesis and DNA binding activity of functionalised iron(II) supramolecular helicates. DNA and the ways that organic and metallo-molecules recognise and bind to it are reviewed. The field of supramolecular chemistry and particularly supramolecular helicates is considered, including those developed as anticancer agents. The design of a novel functionalisation route for the development of functionalised helicates is presented. The synthesis and characterisation of several metallo-helicates functionalised with simple chemical groups, such as hydroxyl and phenyl moieties, is described. Studies reveal that this functionalisation does not inhibit the inherent DNA binding activity of these types of cylinders. The development of steroid-hormone functionalised iron(II) helicates for targeted delivery to cancerous tissues is also detailed, including their synthesis and characterisation. These steroid functionalised complexes bind to DNA, inducing changes in the DNA conformation. The design, synthesis and characterisation of several metallo-helicates functionalised with targeting sugar vectors, is also presented. These sugar-conjugates can bind to DNA, causing intramolecular coiling and unwinding of the DNA helix.

In this project, a gold nanoparticle system has been developed that is able to detect SNP variations through a DNA based anthracene probe. A second probe is bound to the gold nanoparticle which allows the fluorescent output of the anthracene probe to be normalized. This allows the detection of SNP variations without the need for an initial reading, opening the possibility for using this system for cellular SNP identification. Through this work a new method for coating gold nanoparticles in oligonucleotides has been developed. In further work, the use of gold nanoparticles to deliver siRNA into cells and induce gene inactivation was investigated. Efforts to improve the knockdown efficiency of these siRNA-gold nanoparticles were made by integrating a second probe onto the nanoparticle surface, non-specific effects were observed upon addition of this second probe.

The flavoenzyme NTR (nitroreductase nfsB from Escherichia coli) and the prodrug CB1954 (5-[aziridin-1-yl]-2,4-dinitrobenzamide) have been found to be a good potential combination for virus-directed enzyme prodrug therapy (VDEPT). However, wild-type NTR has poor kinetics and binding with CB1954, and the mechanism for the reduction of CB1954 by NTR is poorly understood. The aim of this work has been to investigate, using quantum mechanical computational methods, the potential underlying reaction mechanisms so as to identify the order of electron and proton transfers, and source of the protons, that make up the initial reduction step. Additionally, molecular mechanics and molecular dynamics have been used to examine the nature of the active site of the wild-type enzyme, as well as several mutants, and determine possible binding modes of the substrate. Finally, ONIOM calculations were utilised to examine substrate orientations and electronic states at a quantum mechanical level with key active site amino acids present at a molecular mechanics level. Calculations with the MPW1PW91 density functional and 6-31G** basis set yielded a single gas phase transition state geometry for the hydride transfer from the FMN (flavin mononucleotide) cofactor of NTR to a nitro group of CB1954. Additionally, three reaction profiles were generated which suggest that in the gas phase, the reduction proceeds by electron transfer from FMN, proton transfer , then second proton transfer and electron transfer concerted with N-O bond breaking, regardless of the source (FMN or solution) or order of the protons. Molecular mechanics calculations with the FF03 force field found a binding mode with the amide group of CB1954 bound in the active site of NTR—an orientation ideally suited for an electron transfer mechanism.

This thesis describes the advancement of a flexible and convergent gold-catalysed synthesis of trisubstituted oxazoles, and its application to the synthesis of novel polycyclic compounds. Following on from the initial discovery of this reaction, its scope and limitations have been have been explored, leading to a significant increase in the range of functionality which can be incorporated into the products. This reaction, and the novel structure of the 4-amido oxazole products, was then exploited to allow the construction of other complex molecules. A one-pot reaction cascade has been developed, in which the oxazole formation is followed by an intramolecular Diels-Alder reaction, allowing the rapid construction of polyheterocyclic compounds from simple starting materials. Finally, the synthesis of the first oxazole-annulated imidazolium salts is described. These salts act as precursors to prochiral nucleophilic heterocyclic carbene ligands, the organometallic chemistry of which has been investigated.

In this thesis methodologies for manipulation and control of two different surface-molecule systems are explored. Thermal effects play a key role in all of the mechanisms studied. The first methodology studied is self-assembly of dimethyl-disulfide on Au(Jll). Conformational change and diffusion of Au-adatom dithiolate complexes are investigated over the temperature range 77 K to 200 K. The second manipulation methodology is non-local manipulation of Si(lll )-7x7: PhCI. Non-local desorption of the chemisorbed molecules by hole injection is studied in the temperature range 77 K to 293 K, and compared to previous results on the electron induced process in the same temperature range. It is found that desorption proceeds through the physisorbed state for both carriers, but that there is an additional mechanism which differs depending on the charge carrier. Non-local manipulation of physisorbed chlorobenzene is studied at low temperature, where a new species is found to be created in non-local manipulation experiments at 4.6 K. It is speculated that this is a result of efficient dissociation of the physisorbed molecules.

Diffusion-weighted magnetic resonance imaging (DW-MRI) has rapidly become an important part of cancer patient management. In this thesis, challenges in the analysis and interpretation ofDW-MRI data are investigated with focus on the intravoxel incoherent motion (IVIM) model, and its applications to childhood cancers. Using guidelines for validation of potential imaging biomarkers, technical and biological investigation of IVIM was undertaken using a combination of model simulations and in vivo data. To reduce the translational gap between the research and clinical use of IVIM, the model was implemented into an in-house built clinical decision support system. Technical validation was performed with assessment of accuracy, precision and bias of the estimated IVIM parameters. Best performance was achieved with a constrained IVIM fitting approach. The optimal use of b-values was dependent on the tissue characteristics and a compromise between bias and variability. Reliable data analysis was strongly dependent on the data quality and particularly the signal-to-noise ratio. IVIM perfusion fraction (j) was generally found to correlate with dynamic susceptibility contrast imaging derived cerebral blood volume. IVIM-f also presented as a potential diagnostic biomarker in discriminating between malignant retroperitoneal tumour types. Overall, the results encourage the use of IVIM parameters as potential imaging biomarkers.

The Belousov-Zhabotinsky (BZ) reaction is the preeminent oscillating chemical reaction for the study of pattern formation in reaction-diffusion systems. The dispersal of the reaction in a water-in-oil AOT microemulsion (BZ-AOT reaction) gives rise to an extended range of patterns, including dash waves, segmented spirals and, most notably, stationary Turing patterns that are thought to be significant to an understanding of the biological process of morphogenesis. To date, these patterns have only been observed in two-dimensions using optical microscopy. In this project, nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) techniques were used along with existing optical methods in order to identify redox indicators suitable for the visualisation of pattern formation in the BZ-AOT reaction using MRI. The location of the redox indicator in the microemulsion was found to be important with respect to its application as an indicator. Thus, the use of Ru(II)(bpy)3 as an MR contrast agent was ruled out as it was found to reside within the micellar interface. Manganese, however, proved to be a viable MR indicator. Oscillations were observed in the manganese-catalysed BZ-AOT reaction through changes in the NMR relaxation times of solvent water molecules. The ability of manganese to act as an MR contrast indicator has enabled pattern formation in the BZ-AOT reaction to be visualised using MRI for the first time. Further development of the technique may allow pattern formation to be visualised in three-dimensions.