Bulk samples of the lithium nitridometallates of the general form Li3-xMxN and Li3-x-yMxN, where M = Co, Ni and Cu, x ≤ 0.1 and y = vacancy, have been synthesised. The products of the syntheses have been characterised by Powder X-ray Diffraction (PND), Constant Wavelength Powder Neutron Diffraction (CW PND), Time of Flight Powder Neutron Diffraction (ToF PND), SEM and SQUID magnetometry. The transition metal entirely substituted for the Li(1) at the interplanar site and resulted in a retention of the Li3N-type structure, P6/mmm. These materials displayed similar structural trends as seen in lithium nitridometallates with higher transition metal levels, and with vacancies, which were also dependent on reaction time and temperature at this low level. For longer reacted lithium nitridometallates a large concentration of vacancies was obtained despite a small quantity of dopant transition metal. The resultant charge was deemed too high to be solely balanced by the transition metal, as is usual in these materials. A charge compensation mechanism involving the nitrogen ion was assumed for the high-vacancy materials. The materials displayed some interesting forms of magnetism such as spin-glass magnetic behaviour and also Pauli paramagnetism. Li2.95Ni0.05N and Li2.90Co0.1N displayed a high specific capacity upon electrochemical testing when applied as a potential anode material, and gave better charge capacities than that of the previous best lithium anode material and showed signs of improvement upon cycling. Preliminary investigations into hydrogen adsorption of the materials had been attempted, with one particular material, Li2.95Ni0.05N, giving a hydrogen adsorption of 7.839 wt % over 90 hours with a hydrogen pressure of 20 bar and temperature of 250 oC. A corresponding 3.5 wt % loss was achieved upon desorption at the same temperature.

Supramolecular chemistry involves the study of noncovalent interactions that take place between molecules. A supramolecule or host-guest complex is formed when a noncovalentbinding or complexation event occurs between two such molecules. Hydrogen bonds, electrostatics, ?-stacking, hydrophobic effects and Van der Waals forces are all types of noncovalent interactions. The incorporation of redox active molecules into supramolecular systems is desirable, as they can be used as a convenient way of observing changes in a systems environment. This study involves the synthesis of a range of different redox active molecules, incorporated into supramolecular or materials devices. Firstly, two novel polymerisable flavin monomers have been synthesised. Attempts to polymerise these monomers, followed by characterisation to determine the physical and electronic properties were carried out. Secondly, a porphyrin system capable of binding to a flavin moiety has been prepared, and these complexes have been studied using physical and electrochemical techniques. This system offers an insight into the relationship between the porphyrin and flavin in nature. Furthermore, it would also serve to show how metals in close proximity to the flavin moiety can affect its supramolecular and electrochemical properties. A redox active ureidopyrimidinone system, capable of forming very strong dimer complexes, has been synthesised. This is able to tautomerise in solution, and using a combination of physical and electrochemical techniques, these supramolecular interactions have been studied. A polymer also displaying these properties has also been prepared and studied to understand the supramolecular properties it possesses. The results of this study will hopefully contribute significantly to the body of chemical research in the area of supramolecular and materials chemistry, with a variety of interesting results and scope for further expansion of these projects.

Vibrational spectroscopy has been used to probe the surface chemistry of two heterogeneous catalysts. This has principally involved the application of infrared (IR) spectroscopy and inelastic neutron scattering (INS), with a much reduced role for Raman scattering. Firstly, the activation of high surface area alumina catalysts has been investigated. IR spectroscopy is able to discern the presence of a recently postulated active site. Moreover, INS measurements indicate the potential of this technique to provide additional insight into the surface Lewis acidity of this substrate. The second part of this project uses the reaction of carbon monoxide and hydrogen over an Fe-based catalysts to discern some of the fundamental processes that are likely to contribute to the more complex Fischer-Tropsch synthesis (FTS) process. Ancillary measurements on an industrial grade FTS catalyst validate the procedure adopted.

Proteomics have come a long way since the mid 1990s, with many life-scientists adopting proteomic approaches to understand gene function. Whilst genomic information itself provides an excellent foundation for biomedical research, the complexity of a human cannot be explained by the genomics approach alone. Proteins are the ultimate effector of cell function, thus, studying the dynamic proteome complement of a cell at any given time is a better reflection of the immediate cell environment and its subsequent disease states. Proteins exert their roles in a living organism by interacting with other proteins, so it is believed that a protein's interactions and its functions are related. The study of protein interactions for biological discovery is now routinely carried out in high-throughput formats. Protein microarrays, in particular protein-protein interaction arrays, are valuable tools in protein functional studies, facilitating the unbiased systematic screening for potential interactors. This hypothesis- generating approach is essential in this post-genomic era to bridge the gap between genomics and proteomics, increasing the efficiency of biological research. This PhD describes the functional characterisation of Raf Kinase Inhibitor Protein (RKIP) using protein microarrays for the first time. Whilst the exact physiological role of RKIP remains unclear, RKIP has been associated with an increasing number of diseases, particularly in cancer. This microarray study provided an insight into RKIP’s role in the cell, with the identification of a broad spectrum of interactors not previously associated with its current known function. Findings from this study supported RKIP’s role as a metastatic suppressor, and its function as a scaffold protein. Whilst the advantages of protein microarrays for functional studies are clear, a number of limitations remain. The limitations associated with the current detection strategies in protein microarrays were addressed, with the application of a novel quantum dot-based detection strategy for the detection of protein interactions on microarrays. The performance of quantum dots was comparable to current Alexa-based detection strategies. Biological validation of the novel interactors are routinely carried out by immunoprecipitations (IP) and western blots, which introduces a bottle neck in the high throughput workflow. This thesis reports the development of an integrated co-IP / SILAC (stable isotope labelling by amino acids in culture) approach to compliment the rate of discovery made possible by microarrays.

Amphidinolides T are challenging natural targets for the total synthesis community because of their unique structural architecture. This thesis describes the investigations of the establishment of a novel and convenient route to synthesise four members of the natural product family, amphidinolides T1 and T3-5, from a common late-stage intermediate. The key transformations towards the synthetic pathway are ring formation reactions. The trans-tetrahydrofuran ring is forged efficiently via diastereoselective [2,3]-sigmatropic rearrangement of an oxonium ylide from diazo-generated metal carbenoids. Coupling of a side chain is achieved using a sequence of esterification and RCM reactions. Alternatively, a one-pot RCM followed by hydrogenation is described to shorten the synthetic route.

A new series of a dimeric bis(oxamato) copper(II) complex of formula M4[Cu(oeo)]2 (where Et2H2(oeo) is diethyl ethylene-1,2-dioxamate and M = alkali metal) is described. The complex is formed by two copper(II) atoms and two ligand molecules of which each oxamato group is coordinating towards two different copper(II) ions leading to a distorted square planar environment. Due to the trans-bis(N,O) arrangement around the copper(II) ion, the dimer displays a helicoidal structure. We present here detailed structural studies of this complex with a number of counter ions. Many polymorphs and hydrates are observed and their synthesis and structures are described. A sequential strategy has been developed in which starting from the ligand precursor, Et2H2oeo, the addition of alkali metal hydroxides affords the hydrolysis of the ester leading to the formation of the salt of the ester, M2H2oeo. Then, transmetallation of the alkali metal salt is carried out with the addition of a copper(II) salt. The dimeric copper(II) complex, M4[Cu(oeo)]2, is finally achieved with the addition of the corresponding alkali metal hydroxide. Structural studies of the intermediate compounds are also described. The partial occupancy in the copper(II) site is a common feature in M4[Cu(oeo)]2. Surprisingly, the copper(II) site can be left vacant and the compound still remain with the same helicoidal structure as the non-coordinated ligand, when the amide is protonated, adopting a structurally similar H-bond arrangement. A wide range of copper(II) occupancies have been observed in the different obtained compounds: from compounds with a fully occupied site to compounds with only 10% of copper(II)present in the complex . These differences in the amount of copper(II) present in the complex has consequences in its packing in the crystal structure. The synthesis and characterisation of the copper(II) complex using tetrabutylammonium hydroxide as the counterion is also reported. As a result of the bulky nature of the cation, the mononuclear structure is observed, (n-Bu4N)4[Cu(oeoH)2]. Initial transmetallation reactions are reported with Co(II), in which partial and complete exchange from Cu(II) is observed.

It is widely reported that during periods of inflammation the heme enzyme, myeloperoxidase is generated by macrophages producing reactive oxidative species. Oxidative stress is the imbalance of these oxidative species which will lead to the post translational modification of proteins. Some biomarkers are proteins or post translational modifications that can be used to indicate disease and are becoming increasingly important particularly for the study of progressive diseases. Analysis of biomarkers in bodily fluids will not only be faster and less invasive than a biopsy but will also diagnose disease at an earlier stage and allow disease treatment and progression to be monitored. Known biomarkers for the production of myeloperoxidase are chlorotyrosine and nitrotyrosine. Elevated levels of chlorotyrosine and nitrotyrosine are indicative of atherosclerosis. The early diagnosis of atherosclerosis is important as the onset of this disease can occur at a young age and be asymptomatic until later, more developed stages. Here I aim to develop sensitive methods of detection for these biomarkers in a hope that they can be used to classify disease. A Qtrap mass spectrometer is employed with precursor scan for the selective and sensitive detection of chlorotyrosine modifications in in vitro HOCl modified 9 protein mix samples. Compared to a conventional MSMS experiment the precursor scan detects more chlorotyrosine modifications suggesting it is a better method for the detection of post translational modifications. Additionally the precursor scan can be used when there is no prior knowledge of the modification sites. A multiple reaction monitoring method was developed from the MSMS analysis of in vitro chemical modification of human serum albumin and plasma samples. Observations from the MSMS analysis were employed to write the multiple reaction monitoring method to target for chloro- and nitrotyrosine modified peptides of the human serum albumin protein in plasma samples. Detection of these modified peptides was indicated by the common elution of three transitions specific to the peptides precursor mass. Where anomalous peaks of one transition were seen it was known that this was not the elution of the targeted peptide. The use of three transition masses instead of one reduces the generation of false positives. Where more than one peak for the common elution time was seen for a targeted peptide in the chromatography gradient the retention times were used for identification. Peptides are separated by liquid chromatography prior to their analysis on the Qtrap by their hydrophobicity or their polarity. When a peptide becomes chloro- or nitrotyrosine modified the peptide becomes less polar and therefore is seen later in the gradient than in the unmodified state. The observation of more than one peak where the three transitions are seen to be commonly eluted was caused by break-through of signal from poor selection of a m/z value in Q1. The multiple reaction method developed from the analysis of in vitro chemically modified human serum albumin and plasma was then applied for the analysis of clinical samples in the hope that the chloro- and nitrotyrosine modified peptides targeted for in the samples could be used to classify disease. The clinical plasma samples were sourced from 12 healthy volunteers and 12 diseased cardiovascular patients. The multiple reaction monitoring method indicated the modification of peptides and the presence of these modified peptides was confirmed using targeted MSMS. Classification of these samples was not successful and it was thought that a combination of biomarkers is required for the classification of disease.

The investigation of strongly hydrogen bonded solid state materials and the hydrogen transfer processes therein are the subject of the present work. Strong hydrogen bonds are found whenever the hydrogen bonded species compete for the hydrogen atom, and are thereby on the verge of showing hydrogen transfer. Consequently, the strongly hydrogen bonded solid state materials investigated in this work are synthesised by co-crystallising chemical compounds which have a similar affinity for the proton. The molecular complexes of isonicotinamide with oxalic acid crystallise in two hydrogenous polymorphs and, upon substituting the acidic hydrogen for deuterium, in two deuterated polymorphs, neither being isostructural to the hydrogenous forms. This phenomenon is known as isotopomeric polymorphism and is rarely observed in molecular materials. The four polymorphic forms are found to exhibit different degrees of hydron transfer. The hydrogenous forms show strong hydrogen bonding between the acid and the pyridine base. The nature of these strong hydrogen bonds is characterised by combined X ray charge density and single crystal neutron diffraction studies and found to be covalent in nature. The covalent hydroxyl bonds are considerably elongated, to an extent that in one polymorph the hydrogen atom occupies a near central position in the strong hydrogen bond. The structural work has been complemented by ab-initio computational studies, using the plane wave and localised atomic orbital methods, to evaluate the nature and the dynamics of the strong hydrogen bonds, and to establish an energy scale for polymorphism. It is found that the atomic orbital calculations yield results in good agreement with the experiment, while the plane wave calculations fail to reproduce the experimental hydrogen bond geometries. A strong electronic delocalisation is observed in the difference electron densities of strong acid – pyridine base hydrogen bonds. The major contribution to the delocalisation is found to originate from the nitrogen lone pair density which in this type of strong hydrogen bond is found to be observed to low experimental resolutions in standard X-ray diffraction experiments. As a consequence, such hydrogen bonds are susceptible to misinterpretation, and can be misinterpreted as hydrogen bonds with a disordered hydrogen, altering the descriptive character of materials significantly from being neutral to being ionic. It is shown that a careful examination of the difference electron densities, with the knowledge of the presence of the nitrogen lone pair density, allows a reasonably accurate determination of nuclear hydrogen positions from X-ray diffraction experiments alone. The hydrogen transfer behaviour in a series of strongly hydrogen bonded materials has been studied. For the molecular complexes of pentachlorophenol with the series of dimethylpyridines, a correlation is established between the dissociation constants determined in solution and the degree of hydrogen transfer from phenol to the pyridine bases in the solid state. The influence of additional strong and weak hydrogen bonding interactions in the vicinity of the strong hydrogen bonds on the hydrogen transfer behaviour is rationalised. Similar studies have been carried out on the molecular complexes of oxalic acid and fumaric acid with the dimethylpyridines, and on the molecular complexes of pentachlorophenol with 1,4-diazabicyclo[2.2.2]octane. The design approach leading to these materials and the hydrogen transfer behaviour observed in these materials is critically analysed.

This thesis describes the preparation, structure and activity of a range of binary, ternary and quaternary molybdenum nitrides. It has been shown that all of the samples analysed can be formed through the reaction of the respective molybdate precursor with either ammonia or 3:1 H2/N2 gas mixture. The structures of the nitrides have been studied in detail. These structural findings were then linked to the activity potential of the materials to act as stores of activated nitrogen. The main body of work focused on the ternary molybdenum nitrides of cobalt, iron and nickel with a view to understanding their differences and similarities. Full structural analysis was performed using powder X-ray diffraction (PXRD) and neutron diffraction (PND). The activity of the nitrides was examined by reaction with 3:1 H2/N2 and with 3:1 H2/Ar at various temperatures. Particular attention was paid to the reactivity of lattice nitrogen. The cobalt molybdenum nitride was shown to be special case in this regard where the nitrogen is mobile and relocates within the lattice to a different crystallographic site. This mobility and relocation is concomitant with the loss of 50% of the lattice nitrogen from the system resulting in a phase change from Co3Mo3N to the unprecedented Co6Mo6N phase. The physical and chemical properties of this novel phase have been fully characterised and studied. Interestingly, the isostructual Fe3Mo3N behaves differently and the nitrogen remains fixed and the structure and stoichiometry constant throughout the testing procedure. Further studies of the ternary molybdenum nitrides extended to nickel molybdenum nitride, which was shown to be the least active when tested under both gas mixtures, and analogously to the iron molybdenum nitride the nitrogen is fixed within the β-Mn structured nitride. Further investigations were undertaken, resulting in the successful formation of a series of quaternary nitrides (Fe3-xCoxMo3N). These materials show properties similar to the Co-Mo-N system when the material is cobalt rich and behave similarly to the Fe-Mo-N system when iron rich.

This thesis focuses on the assembly of non-conventional templated polyoxotungstates, specifically on {SeO3} and {TeO3}, which results in the discovery of 47 new polyoxotungstate compounds from the isolated gigantic nanoscale cluster {M2Se9W118+nO416+2n} (M = Mn, Co, Ni or Zn, n = 0; M = Fe or Cu, n =1) to the supramolecular 1D chain {CuTeW17O60}n and 3D network {Ag18Te6W76O271Cl}n. This study demonstrated the complexity of “building blocks library” in polyoxotungstates chemistry in “one-pot” reaction as well as the possibility to assemble the discrete building blocks in a controlled manner, which still represents a big challenge to the inorganic synthetic chemists. The formation of ‘pure’ tungstoselenite and tungstotellurate building blocks can be affected by a few vital reaction variables including, but not limited to, pH, ionic strength, temperature and type of cations. Carefully screening and controlling the reaction conditions can lead to different building blocks which have unprecedented novelty as such types of building blocks have never been discovered before in conventional templated polyoxotungstates, e.g., the lacunary pentagonal unit {(WO7)W4} containing {Se2W29} and {Te3W43}, the layer-shaped [TenW6n+3O21n+12](6+2n)- (n = 1, 2, 3) and so on. Further these building blocks could assemble into various polyanions through different aggregate behaviours. The transition metal ions containing tungstoselenite or tungstotellurate clusters can be reasonably designed and isolated by using a “shrink wrapping” strategy and screening the synthetic parameters such as pH, temperature and ionic strength. These clusters are fully characterized by XRD, ESI-MS/CSI-MS and chemical analysis, IR, as well as by preliminary electrochemical studies. The synthetic methodology is also developed, the combination of building block strategy and stepwise synthesis methods lead to the isolation of a series of new polyoxotungstate compounds including gigantic cluster {Cu9Se12W174O630Cl3} which represents the largest polyoxotungstate cluster containing pentagonal unit {(WO7)W4}. These discoveries lead to a general new polyoxometalate building block approach and start a new field in polyoxotungstate synthesis.