The alignment of the bonds in a molecule or the orientations that individual molecules take with respect to each other in a macromolecular structure is of significant importance to understanding the molecular mechanics and the nature of their interactions with their environment. There are a variety of different techniques available to investigate this matter.1,2 In comparison with other widely used techniques such as crystallography and fibre diffraction, linear dichroism (LD) is simpler to apply, less time-consuming and also gives useful information about the transition polarisations.3–5 In the preliminary stages of this work, we tried to optimise the technique in order to collect data of higher quality than had been previously possible for a wide range of different types of molecules with different characteristics. We invented a new method of orienting polar and slightly-polar molecules by changing the surface of polyethylene (PE) films to have oxygen groups on them,making PEOX. Then we tried to combine the improved orientation and LD spectroscopy techniques with fluorimetry to make fluorescence detected linear dichroism (FDLD) to increase the sensitivity and selectivity of our experiments. As all UV-visible spectroscopy techniques, including LD and FDLD, are limited by the small number of UV-active functional groups (chromophores) in molecules, we then turned to vibrational spectroscopy techniques. In particular, we have worked on a new type of polarised Raman spectroscopy - Raman Linear Difference (RLD) spectroscopy. The first RLD spectra had been published in 2011.6 In this work, we used our new PEOX films and the new Raman spectroscopic technique to study the alignment of molecules in the vibrational realm. After recording high resolution polarised vibrational data for a set of small molecules using a Raman microscopy system, we designed a new polarised Raman spectrometer which was built in the final stages of this project. We evaluated the newly built instrument by repeating polarised Raman experiments we had performed on the microscope system and found that the results were a significant improvement.

Great challenges remain in our understanding of biomineralisation which impede the design and production of a new class of materials. Recent studies have suggested that calcium carbonate clusters are stable in solution before nucleation, and that these participate in the formation of amorphous calcium carbonate (ACC). The structure and stability of these clusters has not been fully determined. Furthermore, the dehydration of stable ACC before crystallisation remains ambiguous. Exhaustive computational searches have been carried out to provide a sample of clusters up to the sizes suggested for particles persisting before nucleation. A large sample of clusters were simulated at high concentration in water using molecular dynamics (MD). The results suggest that cluster stability is a balance between ionic coordination and ion hydration. At high concentration clusters are generally dynamic in the lower limit of stability, forming chains to which ions frequently aggregate and dissolve. Free energy calculations showed a transition in the favoured coordination levels with cluster size. One dimensional Umbrella Sampling calculations showed that at small sizes a collection of clusters with low average cation–anion coordination were thermodynamically stable. For systems containing sixty ions and above, more compact clusters with internal water, close to the stoichiometries identified for stable hydrated ACC in vivo, were lower in free energy. From MD simulations at experimental concentrations and pH, while dynamic ordering was found, ion pairs dominated in solution and the largest clusters observed contained no more than four ions. These findings, combined with the data at high concentration, allow for a re-evaluation of the proposed nucleation mechanisms for calcium carbonate from solution. ACC simulations identified water–filled channels within the ionic framework. Percolating clusters were found when H2O/CaCO3 was greater than 0.75–0.8. The ACC system fitted well with the percolation theory on a simple cubic site lattice for water, and critical exponents showed a good fit to the theoretical values. Non–standard diffusion was found for water, with a “jump” mechanism of diffusion observed and a cascade of molecule displacements within channels. This original result allows new light to be shed on the dehydration mechanism of ACC.

The aim of this work, sponsored by Lubrizol, was to develop polymers for potential use as novel viscosity modifiers for automotive oils. The broader scope was to build towards the incorporation of stimuli-responsive behaviour (temperature, shear, pH etc.), since there is currently no such technology on the market which does so. The Haddleton group has developed expertise in Cu(0)-mediated RDRP techniques, and so these were utilized throughout the thesis. As a starting point, α,ω-functional lipophilic poly(butyl acrylates) were synthesized, which were then functionalized post-polymerization using thio-bromo substitution with a view to inducing associative thickening. During this investigation, a novel biphasic reaction scheme was noted, wherein the polymer was observed to phase separate from the solvent/catalyst mixture. Additionally, some previously unreported ligand effects were found. The incorporation of ureido-pyrimidinone hydrogen bonding motifs to lipophilic poly(acrylates) was also pursued, with the subsequent materials showing interesting rheological characteristics. The biphasic Cu(0)-mediated RDRP system was then used to synthesize poly(lauryl) and (butyl acrylate) star polymers with exceptional degrees of control over the molecular weights and dispersity. These reactions were then successfully scaled up to produce enough materials to undergo some standard industrial tests, to assess their suitability as VMs. Lastly, a collaborative side-project was also undertaken which moved away from generating oil-soluble polymers to examining the feasibility of grafting poly(NiPAM) brushes from water purification membranes using aqueous ‘SET-LRP’. This was shown to be possible, as demonstrated using a range of surface analysis techniques.

This thesis is divided into four chapters in which one-pot processes have been developed and utilised for the synthesis of biologically active compounds. The work in the first chapter outlines the 13-step total synthesis of D -ribo- and L - arabino-phytosphingosine from D -ribose. This process employed a microwave promoted Overman rearrangement of an allylic trichloroacetimidate to install the amine functionality. In the second and third chapters, the development of a one-pot, two-step Overman/ring closing metathesis process is detailed. The synthesis of three different classes of starting material is also shown. This one-pot process was used as the key step in the synthesis of four oxybenzo[c]phenanthridine natural products and the partial synthesis of an ACAT inhibitor. The potential for further functionalisation of the products by oxidation and reduction was also explored. In the final chapter, a one-pot allylboration/Heck process for the synthesis of indan-1-ols is described. Optimisation and an investigation of the scope of the process are also presented. The process was then altered to allow the use of a chiral phosphoric acid catalyst for the asymmetric synthesis of these compounds.

Polyetheretherketone (PEEK) is a polymer with outstanding performance, particularly concerning temperature resistance, chemical resistance and mechanical characteristics. Literature shows a gap in the knowledge with regards to PEEK flammability and decomposition products. The aim of this thesis is to describe the decomposition and flammability behaviour of PEEK, in order to develop new fire safe PEEK-based materials. By relating the measured thermal decomposition behaviour and changes in physical properties of PEEK materials to their performance in standard flammability tests, the dependence of these tests has been investigated with regards to orientation, thickness, presence of fillers, moisture absorption and absorption of infrared radiation. This understanding can inform the development of modified PEEK materials with enhanced fire safety. Various industry standard tests have been utilised to examine PEEK such as the Cone Calorimeter (ISO 5660), UL-94 (EN 60695-10-11), Limiting Oxygen Index (LOI), Thermogravimetric Analysis (TGA) in both air and inert atmospheres and the Small Flame Ignitability Test (ISO 11925). PEEK decomposition has been investigated using Thermogravimetric Analysis (TGA), Simultaneous Thermal Analysis coupled with Fourier Transform Infrared (STA-FTIR) and Pyrolysis Gas Chromatography coupled with Mass Spectrometry (pyGC/MS). Residue analysis has been carried out using Diamond Attenuated Total Reflectance coupled with Fourier Transform Infrared (dATR-FTIR), Solid State Nuclear Magnetic Resonance (MAS-NMR) and Scanning Electron Microscopy coupled with Electron Dispersive X-ray Analysis (SEM-EDX). Thermal analysis shows a rapid mass loss around 580°C followed by a slower mass loss of the resultant char. The stages of decomposition have been investigated by using FTIR and NMR on the condensed phase residues. Samples subjected to various temperature regimes have been observed in the dATR-FTIR and MAS-NMR and the results shows differences in the structures of the residue during decomposition. Generally, filled PEEK materials (with glass fibre, carbon fibre and talc) tend to have lower flammability in the Cone Calorimeter with a longer time to ignition and a lower peak heat release rate compared to the unfilled materials. The same is true in the LOI, where filled materials give a higher oxygen index, and in the UL-94 test where shorter burn times are recorded. PEEK shows inconsistent behaviour in some flammability tests, possibly due to the critical heat flux for ignition of PEEK being so close to the heat fluxes employed in many industry standard tests. The presence of moisture within the samples also reduces the time to ignition of PEEK in the Cone Calorimeter and increases the burning time in the UL-94, possibly due to the formation of a foamed sample close to the melting temperature of the polymer.

Gunshot residue (GSR) mixture consists of partially burned particles of propellant and characteristic particles of elements originating from the primer, bullet, propellant and some additives in the propellant. Since Harrison and Gillory [1] drew forensic scientists’ attention to the fact that GSR contained trace amounts of inorganic compounds such as lead, barium and antimony, a number of analytical techniques have been tested trying to find and establish sensitive, selective and reliable methods to identify and analyse gunshot residues. The standard procedure for the analysis of gunshot residues involves imaging these small metallic particles using scanning electron microscopy (SEM) and subsequent compositional analysis using Energy Dispersive X-ray Analysis (EDX). This study focuses on the analysis organic compounds in GSR. It is motivated by the increasing need to overcome the problems with the analysis of lead-free ammunitions. A comprehensive literature review was performed in order to determine the most commonly encountered organic compounds in GSR. These compounds include diphenylamine, methylcentralite, ethylcentralite, nitroglycerine, 2-nitrodiphenylamine and 4-nitrodiphenylamine. It has been clearly demonstrated using standard materials and appropriate calibration curves that gas chromatograph and mass spectrometry (GC/MS) is capable of providing limits of detection that are consistent with the concentrations of the key organic constituents found in gunshot residues. Furthermore, we have demonstrated that the relative concentrations of seven key components can be used to provide branding information on the shotgun cartridges. A strong relationship was found between the chemical composition of fired and unfired powder. Therefore, it is possible to differentiate between two ammunition brands through the analysis of the organic constituents. Traditional fingerprint powders such as titanium dioxide, aluminium, carbon black, iron oxide, lycopodium spores and rosin are used to enhance fingerprint left at the scene of crime. More recently nanoparticles have been demonstrated to be highly effective for the enhancement of the fingerprints [2]. Silica nano-particulates of defined size and shape were synthesised and functionalised with two different functional groups (phenyl and long chain hydrocarbon) using a Tri- phasic Reverse Emulsion (TPRE) method. These nano-particulates were characterised using scan electron microscope (SEM), transmission electron microscopy (TEM), elemental analysis, particles size analyser, BET surface area and solid-state nuclear magnetic resonance (NMR) spectroscopy. These powders were used as an effective agent to visualise latent fingerprints on different surfaces. Furthermore, they have been utilised to absorb any organic materials within the fingerprint from the discharged of weapon. Analyses of the adsorbed organic residues were performed using GC/MS and Raman spectroscopy. The results showed that the synthesised silica nano-particulate fingerprint powder gave better result in term of their ability to absorb organic materials in GSR and enhance the visualisation of the latent fingerprint compared to a single commercial powder.

Hydrogenation is one of the major processes used in commercial and academic applications in the manufacture of chemical intermediates; high tonnage products of high value, and useful chemicals, such as agrochemicals and pharmaceuticals. Free solvent hydrogenation of cyclohexanol using Au, Au:Pd and Pd/CsxH0.5PW12O40 catalysts have been performed in the liquid phase. Reaction conditions, for example supports with/without Cs-salt loading, metal loading and/or ratio were varied to achieve ideal conditions. The Palladium supported on Cs2.5H0.5PW12O40 is a successful catalyst for such hydrogenation, and Cs2.5H0.5PW12O40 has been shown to be the best of the supports investigated for the preparation of catalysts using the impregnation method. Pd, Au and Au:Pd catalysts supported on TiO2 have been used for the hydrogenation of furfuryl alcohol and furfural with H2 at room temperature. The influence of the pressure, catalyst mass, support, Au:Pd variation, Pd loading and solvent have been investigated. In addition, Ru and Ru:Pd was studied with furfural, and also the effect of Ru:Pd ratios. The selective hydrogenation of both Furfuryl alcohol and Furfural into 2-methylfuran was investigated at room temperature using Palladium supported catalysts. This study has shown that Pd/TiO2 catalysts can be very effective for the synthesis of 2-methylfuran at room temperature and low pressure hydrogen (1-3 bar). The effect of various reaction conditions (pressure, catalyst amount, and solvent) has been studied. Controlling the catalyst composition can control the selectivity to molecules with multiple functioning groups, and reaction conditions can promote or hinder the various reaction pathways, thus increasing selectivity to the desired hydrogenation yields.

This work describes the development and the optimisation of microfluidic radiolabelling by using an Eckert & Ziegler device remotely controlled by a computer to perform the multistep synthesis of [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG). This device was then modified to control the fluidic transfers via flow of nitrogen and vacuum with the aid of a new one-way cassette system by using different concentrations of water for the Kryptofix solution. A new route was also explored to perform florbetaben ([18F]-BAY94- 9172), a potent Alzheimer’s disease PET tracer. Chapter 1 is an overview of positron emission tomography techniques to synthesise tracers. Chapter 2 is a brief introduction of the PETIC centre (Wales), where the fluoride-18 was delivered to produce [18F]-FDG. Chapter 3 describes the reaction of the [K+⊂2.2.2]18F− complex on mannose triflate and the variety of products formed. The Eckert & Ziegler platform was furnished with a cassette module and a microfluidic tubing to perform the radiolabelling fluorination of mannose triflate to the tetraacetate [18F]-deoxy-D-glucose and [18F]-FDG. Chapter 4 is focused on the modifications on the Eckert & Ziegler modules by using 1-way cassettes to limit the use of mechanical valves. [18F]-FDG was synthesised via a semiautomated procedure by limiting the number of modules present in the hot cell. Chapter 5 is an investigation for the preparation of several triethylene glycol derivatives following the syntheses of Kryptofix [2.2.2]. The use of triethylene glycol chain will be essential for the synthesis of the Florbetaben precursor. The Chapter 6 is the exploration of a new synthetic route leading to the precursor of florbetaben.

This thesis details the synthesis of non-linear, acid functional polymers and their application to photo-curable polymer-inorganic dental composites. Many polyacids containing photopolymerizable groups used in current materials require multi-step synthesis and purification, due to the toxic solvents and reagents used. This work describes the synthesis of non-linear polyacids containing vinyl functionality that can be synthesized in a one step process, using non-toxic, aqueous media, as well as their subsequent testing in glass ionomer cements. Initial work in Chapter 2 set out to investigate the feasibility of synthesizing low molecular weight linear poly(methacrylic acid) (PMAA) via Catalytic Chain Transfer Polymerization (CCTP). The process was found to proceed efficiently, with good control over the molecular weight achieved by varying concentration of the chain transfer agent (CTA). Work then moved toward the incorporation of the less CCT-active acidic monomer, acrylic acid. It was found that the monomer reactivity ratios for the CCT copolymerization led to substantial compositional drift during the reaction and the formation of high molecular weight species. Additionally, multidetector size exclusion chromatography (SEC) analysis revealed the formation of non-linear polymer architectures, likely due to the CCT-derived vinyl group participating in propagation leading to an extent of grafting. The copolymerization of MAA with the difunctional monomer ethylene glycol dimethacrylate (EGDMA) was then investigated in two aqueous solvent systems. It was found that conducting the copolymerization in water led to a biphasic system at the outset of polymerization. This solvent system yielded a branched polymer of higher molecular weight and dispersity than analogous products synthesized in homogeneous solutions in water/IPA. The presence of a high level of vinyl functionality was confirmed using a bromination-titration methodology and the branched architecture revealed by multi-detector SEC. In Chapter 3, the linear and branched polyacids synthesized were then applied to dual-cure glass ionomer cements (GICs), a class of polymer-inorganic composite materials. A model photo-polymerizable GIC system was established via optimization of a three component, camphorquinone based photo-initiating system and investigation of the effect of additives and polymer concentration on the curing of the cement. This model system was used to investigate the influence of the polymer component on the final cement, with polymers of higher molecular weight generally leading to cements with greater compressive strengths. The resulting materials were characterized using a range of online monitoring techniques, including photo-DSC, photo-rheology and in situ FTIR, and the final cements’ compressive strength tested. Several methacrylate-modified PAAs were also synthesized in order to investigate the effect of photo-polymerizable functionality, and their properties compared to those of the linear and branched PMAA-based materials. It was found that the acrylic polymers led to cements with substantially higher compressive strengths than both the linear and branched methacrylic systems. However, the methacrylate-modified PAAs were found to give compressive strengths of similar magnitude to commercial materials, verifying that the relatively simple materials developed were an appropriate model system for this investigation.

Chapter 1 | Reviews innate host-defence α-helices and their mimetics as potential anticancer chemotherapeutics. Introduces biologically relevant bimetallic triple metallohelices as potential non-peptide mimics, and reviews the known flexicates. Discusses the criteria such compounds would need to satisfy in order to be successful anticancer agents. Chapter 2 | Describes the discovery, synthesis and characterisation of nineteen new class Ib flexicates with varying ligand functionality. These compounds are found to be highly active and selective in cancer, with no observed activity in bacteria. Preliminary modes of action studies indicate that they do not act through DNA interactions, but cause changes to the cell cycle and induce programmed cell death. Chapter 3 | Describes the conception, synthesis and characterisation of a new asymmetric type of architecture, named a triplex metallohelix. A range of these novel complexes are found to be highly active and selective in several cancer cell lines. Possible modes of action found the triplex metallohelices do not bind or damage DNA, but do cause changes to the cell cycle, induce programmed cell death and appear to localise on the cellular membrane of colon cancer cells. Chapter 4 | Summarises the aims and results of this research project and concludes this work by discussing the perspectives of the novel metallohelices described as α-helix mimetics. Final remarks consider some possible directions that this research could take in the future. Chapter 5 | Provides details of the experimental procedures used to carry out the work in this thesis.