In recent years, the molecular chemistry in interstellar environments has proven to be far more complex than was initially expected. We live in a molecular universe that is rich with molecules formed both in the gas phase and on the surface of interstellar icy dust grains. Two important classes of interstellar molecules are sulphur-bearing species and complex organic molecules, i.e., molecules containing carbon and containing more than 6 atoms. The former are relevant because of their potential utility in establishing the age of star forming regions. The latter are important because they are excellent probes of the physical conditions of the regions where they reside. Moreover, complex organic molecules are thought to be astrobiologically relevant. To properly understand the chemical networks leading to the formation of astrochemical species, to date more than 170 have been conclusively identified, the integration of laboratory experimental data with existing computational models is paramount. Laboratory studies can be conducted in the gas phase or, as is the case for this work, in the solid state. Studies of the processing of ices, by thermal energy or by ultraviolet radiation, are particularly important in understanding solid phase chemistry in the interstellar medium. In this thesis, the results of laboratory experiments aiming to mimic the physical/chemical reactions of ices on interstellar dust grains are presented. Specifically, temperature programmed desorption and reflection absorption infrared studies were carried out in an ultra high vacuum setup on H2S (chapter 3) and on the C2H4O2 isomer family (chapters 4 and 5) formed of acetic acid (CH3COOH), glycolaldehyde (HOCH2CHO) and methyl formate (HCOOCH3). Ultraviolet irradiation studies of glycolaldehyde have also been performed, and the results of these are presented in chapter 6. In order to put the laboratory results into an astrophysical context, computer simulations of the desorption of these species from interstellar grains were conducted. The results for H2S are presented in chapter 3. Those for acetic acid, glycolaldehyde and methyl formate are presented in chapter 4.

This thesis describes and investigates novel strategies for cysteine modification to achieve protein bioconjugation. Chapter 1 provides an introduction to the research project with an overview of protein modification techniques. Chapter 2 describes the development of a site selective dual labelling strategy based on substrate controlled cysteine modification. The application of this strategy to green fluorescent protein is also detailed. Chapter 3 describes the development and evaluation of thiophosphonium as a platform for protein modification. An in-depth discussion on reaction mechanisms, pathways, stability of thiophosphonium and the utility of this platform is also included. Chapter 4 describes the development of bromomaleimide based reversible cysteine modification, with particular focus on development of improved strategies for conversion of thiomaleimides back to free cysteines. The utility of the approach was demonstrated using a proof of concept experiment.

This thesis is concerned with the deposition of titanium dioxide thin films using chemical vapour deposition (CVD). The work emphasises the influence of deposition parameters on the properties of the resultant film. The materials have been designed with a wide range of potential applications in mind, from air and water purification to energy production and medical implant devices. Where possible, tests have been conducted to assess the efficacy of the material for these applications. The first chapter highlights a number of technologically important applications of titanium dioxide in order to demonstrate the motivation for research in this area. Some theoretical concepts are presented which are fundamental to understanding the behaviour of titanium dioxide. The principles behind chemical vapour deposition and the photocatalytic tests used in this work are discussed. The second chapter focusses on the use of three different metal substrates in TiO2 CVD. Firstly, the phase of TiO2 deposited on steel substrates was investigated. It was shown that the grade of steel had little influence with predominantly anatase films being formed in the vast majority of areas analysed. Since each grade of steel has different mechanical properties and is used in different applications, this work demonstrates that the photocatalytic properties of anatase films can be endowed to a large range of products. Secondly, TiO2 was shown to be adherent to a flexible substrate, namely aluminium foil. It was demonstrated from XPS analysis that aluminium ions did not diffuse into the TiO2, which remained photocatalytically active. A photocatalyst on a lightweight, flexible substrate offers several advantages over glass which has been the most frequently employed substrate to date. Thirdly, titanium dioxide was coated onto an alloy of cobalt, chromium and molybdenum, CoCrMo. The alloy is of interest for biomedical implants but suffers from poor biocompatability. By coating its surface with TiO2, it was shown to enhance osteogenic differentiation. Chapter three investigates nitrogen doped titanium dioxide for its potential as a visible light photocatalyst. A novel synthetic strategy was employed in which the amount of oxygen precursor was varied to determine if this would affect the position of the nitrogen in the titanium dioxide crystal structure. Differences were observed in the nitrogen XPS signal, the absorption profile, surface morphology and photocatalytic activity under both UV and visible irradiation. Visible light activity was observed for a sample made with lower amounts of oxygen precursor under UV and visible light. Finally, brookite, a rare, metastable form of titanium dioxide, was formed by atmospheric pressure chemical vapour deposition, APCVD. A brief literature review discusses the potential applications and some of the previously employed synthetic routes to brookite formation. Three sets of conditions are reported for the first known synthesis of brookite by atmospheric pressure chemical vapour deposition. A possible mechanism for brookite formation is hypothesised. This work concludes with a summary of the key findings from the experimental work and possible avenues for further research.

The project investigated the development of peptide-based nanotools for applications in cell biology. Differential intracellular and membrane targeting was probed using rationally designed cell penetrating and antimicrobial peptides. The interaction of the peptides with bacterial and mammalian membranes was imaged using a combination of atomic force microscopy (AFM) and highresolution secondary ion mass spectrometry (NanoSIMS). This approach provided unique information on the topography of peptide-treated membranes, obtained from AFM images, suggesting membrane changes as a result of peptide structuring and pore formation. The data was complemented by chemical imaging performed on the same samples with NanoSIMS, which revealed the precise localisation of peptide molecules in the membranes. In parallel, multidimensional protocol for tag-free quantification of cellular uptake of cell penetrating peptides, based on chromatographic separations and followed by isotope dilution mass spectrometry was developed. The amount of the designed peptide, internalised by human dermal fibroblasts was evaluated and compared to the uptake of a broadly studied and well characterised naturally occurring peptide. The results were compared to the peptide uptake quantified using confocal fluorescence microscopy. The studied synthetic peptides were also investigated as model systems to functionalise metallic nanoparticles (NPs). Characterisation and functionalisation of the NPs were carried out. To prevent a non-specific physisorption of molecules, the surface of NPs was passivated by coating with lipid bilayer or polyethylene glycol. Finally, using cross-linking chemistry, the designed peptides were conjugated to the coated particles and their interaction with mammalian and microbial cells was investigated by transmission electron microscopy. The results of this work indicate that rationally designed peptides carry the potential for being employed in the development of nanoscale, multifunctional probes for differential and specific intracellular and extracellular targeting.

This thesis investigated the reactivity of the metal chlorides TiCl4, VOCl3 and VCl4 with different organic ligands. The chosen ligands were based around the chemical structure of soya oil due to its relevance to the industrial chlorine process used to manufacture TiO2. This thesis primarily used nuclear magnetic resonance (NMR)spectroscopy to characterise the reactions of the metal chlorides with soya oil and component parts, namely the glycerol and the alkene. This thesis goes on to investigate the coordination chemistry of the metal chlorides with ligands including diester groups. The chemical properties of the metal chlorides are known to be similar and hence hard to separate, the reactions studied provide a mechanism for their separation using diesters. It will be shown that TiCl4 coordinates with the ligands without the loss of any chlorine atoms and without disrupting the ligand. The VOCl3 reacted with the ligands, releasing a chlorine atom to produce a VOCl2 adduct. The difference in reactivity provides a removal mechanism. In the industrial process TiCl4 is present in very high concentrations and the coordination of TiCl4 can be seen as reversible and in equilibrium. Whereas, the VOCl3 converts VOCl3 into VOCl2, VOCl2 has a higher boiling point and can therefore be removed by distillation.

This thesis describes the discovery and development of new routes towards substituted indoles and ynol ethers based on a sulfonate and sulfonamide leaving group, respectively. Both syntheses involve the use of these electron-withdrawing moieties as α-radical stabilising groups that can be utilised in a range of mild and facile bond-forming reactions to yield useful organic compounds. The first approach describes the synthesis of indoles utilising a water soluble, phosphorus-based chain carrier that generates a carbon-centred radical from an sp3 bromo sulfonate ester. This species can consequently undergo an intramolecular cyclisation with an aromatic ring, followed by loss of the sulfonate ester to yield a range of indoles in a chemoselective fashion. The second part of this thesis describes the synthesis of a range of ynol ethers via reaction of an aliphatic potassium alkoxide with an aromatic alkynyl sulfonamide. The mechanism of this process has been explored via a combination of synthetic chemistry and electron paramagnetic resonance spectroscopy (EPR) and the findings of these experiments will be discussed. The synthesis of tert-butyl ynol ethers in particular, allows for retro-ene decomposition to yield a ketene. This reactive intermediate can consequently undergo [2+2] cycloaddition with a ynol ether to yield tri-substituted cyclobutenones in excellent yield. Based on these findings, a new mode of reactivity for potassium alkoxides is suggested that involves these compounds ionising at room temperature under certain conditions to form either stabilised alkoxyl or trioxyl radical complexes that are observable via EPR, where the latter complex is known to decompose to alkoxyl radicals and molecular oxygen. The work presented in this thesis may have implications for other areas of science such as atmospheric chemistry and transition-metal free cross-coupling chemistry.

The application of yttrium-based glasses as radionuclide vectors for in situ radiotherapy relies on the durability of the glass in a physiological system: leaching of activated 90Y ions from the glass matrix into the bloodstream should be minimised as much as possible immediately after injection and before their radioactive decay. In order to understand the relationship between glass composition, structure and durability at an atomistic level, classical molecular dynamics simulations were carried out on different yttrium-containing silicate-based glass compositions, specifically three yttrium aluminosilicate glasses: YAS17, 24 and 30, where 17, 24 and 30 denote the molar % of yttrium, as well as yttrium-containing bioglass (YBG) with and without the presence of phosphorus. Each of the glass compositions listed were hydrated at three levels of included water content. The present simulations primarily aim at understanding how different water content influences the bulk structural features critical for the glass durability, such as the network connectivity and nanosegregation. The dry yttrium glasses were thus hydrated with increasing water amounts, and the analysis of the structures has highlighted marked hydration effects on network-former and network-modifier coordination, as well as on the preferential aggregation of yttrium ions, regulated by surrounding OH groups. Hydration of YAS (with increasing yttria content) and YBG (with and without phosphorus) is shown to increase glass durability through strengthening of the silicate network, which is important for the durability of such glasses in radiotherapy applications. Hydroxyl groups have been found to have a preference to coordinate more towards network modifiers than network formers, which is common to both YAS (with increasing yttria content) and YBG (with and without phosphorus). Other results are also discussed, mainly in the context of the physico-chemical characteristics which make yttrium glasses suitable for in situ radiotherapy.

This thesis describes progress towards the use of thio-maleimides as intracellular delivery vehicles. Initially, we describe efforts towards the synthesis of a Förster resonance energy transfer (FRET) maleimide for biological proof of concept experiments. We then go on to demonstrate the potential use of thio-maleimides as intracellularly cleavable moieties that can be used to deliver cargo by the development of “turn-on” reporter molecules and a pro-drug. We have synthesised a number of quenched dansyl-maleimide conjugates as “turn-on” reporter molecules. We have performed conjugate substitution reactions with the intracellular antioxidant glutathione and our quenched fluorophore-maleimide conjugates, to release the fluorophores under approximately physiological conditions. Kinetic studies of these reactions were performed. Cellular experiments confirm this reaction also occurs in biological systems, thus supporting the viability of the use of thio-maleimides as intracellular delivery vehicles. We then optimised the insertion of maleimide into small molecule disulfides. This was in order to insert maleimide into Psammaplin A, a natural product prod-drug. We thus synthesised a thio-maleimide prodrug that proved to be efficacious in biological studies.

Transparent conducting oxide (TCO) thin films were synthesised by different chemical vapour deposition (CVD) techniques, including aerosol-assisted CVD (AACVD) and atmospheric-pressure CVD (APCVD). Such methods were used to control deposition of primarily SnO2-based TCO films, as well as TiO2, allowing for in-depth analysis of properties for improved control and functionality. Investigations were carried out using a variety of techniques including x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS), ultraviolet (UV) Transmittance-Reflectance, Raman spectroscopy and Hall Effect probe measurements. Variation of AACVD deposition parameters in an attempt to improve overall SnO2-TCO properties illustrated how a metathesis reaction (a halide exchange at the Sn-centre) in the precursor is an important step for the formation of high-performing films. Such deposited films exhibit values comparable to the best-performing commercial materials (sheet resistances as low as 3 ohm/square for a 600 nm thick film and figures-of-merit often greater than 2) depending on the defect site identity of the extrinsic dopant. Exploration of various dopant effects on the SnO2 system were also carried out. Fluorine, commonly regarded as the best halide dopant, was confirmed as such (with optical transmittances of 81 % and sheet resistances of 7 ohm/square for a 698 nm thick film), as compared to the other halides. Furthermore, a non-competitive, double-substitutional doping of the SnO2 system, concurrently utilising fluorine and various metal dopants, yields novel methods for control of TCO film morphology (and the attendant optical haze characteristics) and improved electrical properties (resistivities of the order of 10-4 ohm.cm and carrier concentrations of 1020 cm-3 or higher). Such control is highly useful in tailoring TCO functionality to its use, so maximising effectiveness and output for commercial applications. The final chapter explores a novel TCO system, TiO2, and its potential as a TCO material, coupled to its more established materials (e.g.; photocatalytic and wetting) properties. Experimental APCVD values of systems doped with dopants such as uorine, niobium, nitrogen and tungsten (with resistivities ranging 10-1 - 102 Ω.cm and optical transmittances of approximately 70 %, extending into long-wavelength regions) show it is an interesting material worthy of study but that further improvements are clearly required to make it a commercially viable TCO system. The improved mechanistic understanding and synthetic control afforded by the work presented in this thesis should help prepare thin film crystalline TCO systems to meet demands for the next-generation of functional materials applications.

The use of chemical reagents for the modification of peptides has broad applications and, as a result, is a rapidly expanding area of research. Such methods serve to improve the pharmacokinetic properties of the peptide or add functionality for a desired application. Chemical modification of peptides has facilitated the development of a variety of bioconjugates for use as analytical probes, diagnostic agents and therapeutics. This project focuses on the modification of peptides by targeting disulfide bonds. Many peptides contain disulfide bonds which serve a crucial role in retaining their structure, function and stability. Reduction of these disulfides affords two reactive cysteine thiolates whose nucleophilicity can be exploited in peptide modification. To this end, a family of 3,4-disubstituted maleimide reagents were synthesised, designed to efficiently re-bridge a reduced, accessible disulfide bond. The bridging reagents vary in reactivity, properties and functionality but all serve to maintain the structural integrity conferred by a disulfide bond. With these reagents in hand, the scope of their utility was tested on peptides of biological and medicinal interest. One such peptide was tertiapin Q, a neurotoxin derived from the venom of the honey bee and consisting of two disulfide bonds in close proximity. Both singly and doubly bridged variants of the peptide were synthesised and isolated. Biological activity of the modified peptide was analysed by whole-cell patch clamp experiments on cells expressing the target of the peptide toxin, the G-coupled inwardly rectifying K+ (GIRK) channel, which tertiapin Q is known to inhibit. Loss of biological activity was observed upon modification, which led into a full structural characterisation study to determine the explanation for this intriguing result. A second peptide target, octreotide, a stabilised analogue of the hormone somatostatin with a single disulfide bond, was modified with relative ease. Biological activity was examined by whole-cell patch clamp on cells expressing the target of octreotide, the somatostatin receptor (SSTR) subtype 2. Pleasingly, nanomolar activity of the modified peptide was observed. A novel candidate for the next generation of diagnostics for SSTR positive tumours was subsequently developed, characterised and tested by confocal microscopy.