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The thesis describes the use of polycyclic quinodimethanes and related compounds as reactive intermediates in the synthesis of polycyclic aromatic and heterocyolic systems, some of which are novel. Following a general introduction (Chapter I), Chapter II describes the reactions of 5,6-chrysaquinodimethane to give dimers, and its reactions with various dienophiles; including 1 ,4-naphtho­ quinone, with which it gives a novel ring system. Chapter II describes the reaction of 9,10-phenanthraquinodimethane with 1,4-naphthoquinone and attempts to synthesise 6,12-chrysaquinone from chrysene. The reactions of 9 ,10-anthraquinodimethane with various dienophiles are described (Chapter III) while Chapter IV describes the reactions of 9-methyleneanthrone and 1O-methyl-10-hydroxyanthrone with dimethyl aoetylenedicarboxylate and diethyl azodicarboxylate. Chapter V describes the reactions of 1, 1-diphenylethylene with various dienophiles to give novel adducts; and Chapter VI describes the preparation of endo-adducts of anthranol.

The heats of decomposition of some transition metal complexes have been measured by (a) adiabatic reaction calorimetry and (b) differential scanning calorimetry. Method (a) was applied to dichlorobis(triphenylphosphine) cobalt (II) chloride while method (b) was applied to a considerable number of complexes between divalent metal halides and organic bases. These bases were pyridine, methyl-pyridines, aniline, pyrazine, methylpyrazines and pyrimidine. The thermal data which were obtained yielded useful information which may be summarised as follows: (i) Steric interactions The effect on the strength of the metal-nitrogen bond of methyl substitution was investigated. It was found that, for the methyl pyridines, a-substitution was effective in weakening the bond strength. It is, however, not yet understood why B-substitution appears to weaken the bond still further. Very little weakening, on methyl substitution, could be observed for the pyrazine complexes. (ii) Crystal field effects Certain thermal quantities, related to the heats of gas phase reactions, have been calculated from the experimental data. These, when plotted against atomic number for a particular type of complex, vary in the same manner as the crystal field stabilisation energy. One such plot was used to calculate the stabilisation energy of dichlorodipyridinenickel(II) and gave good agreement with a spectroscopic measurement of the same quantity. (iii) Polarisability The experimental data appear to support arguments based on the polarisability of the halogen ligand and the effect of this on metalnitrogen bond strength. n-bonding effects are proposed to account for the apparently constant metal-nitrogen bond strengths in the compounds which contain octahedral molecules. In connection with this, it is shown that there is a convergence of the heats of formation of octahedral and tetrahedral compounds after correction for crystal field effects. Since many of the decompositions were carried out at high temperatures (up to 500oC) it was necessary to calculate the magnitude of the temperature correction to the heats of decomposition required to refer them all to a common temperature. This required values for the heat capacities of the complexes and these were measured, for representative complexes, in the differential scanning calorimeter. The heat capacity data indicated, also, a rigidity in metal-pyrazine bonds which may be due to back n-donation from the metal to the ring.

The interaction of styrene and its unsaturated and saturated dimers (10-5 to 1 M) with conc. sulphuric, or chlorosulphonic acids, and with anhydrous perchloric acid (10-4 to 1 M ) in methylene dich1oride, has been studied and related to the behaviour of other similar systems, such as ~-methylstyrene and its dimers. The origin of the u.v. and visible absorption spectrum which had been wrongly attributed to the l-pheny1ethyl cation and its higher homologues was established:. a) the 3-methyl-l-phenylindanyl cation, and its higher homologues constitute most of the ionic species formed when styrene and its dimers interact with HCI04 in CH2C1 2,. b) the 1,3-diphenyl-n-butyl cation and its higher homologues are formed when styrene and its unsaturated dimer interact with conc. H2S04 and HS0 3 Cl at low temperature and concentration, and this ion has been characterised. The u.v. - visible and n.m.r. spectra of carboniurn ions derivable from the cyclic dimer of styrene were investigated, and spectroscopic correlations were established in the following series of diphenylalky1 cations: diphenylmethyl and ethyl, phenyl-(2' methylphenyl) methyl and ethyl, phenyl-(2'-ethylphenyl)methyl and ethyl (all l,l-ethyl), 1 ,1-dipheny1-n-butyl , l-phenylindanyl and 3-methyl-l-phenylindanyl.

Failure to monitor the condition of key infrastructure such as roads and bridges can result in costly closures, but the economic impact could be lessened by early intervention. Non-destructive testing (NDT) examines structures without causing damage, while structural health monitoring (SHM) monitors a structure throughout its life. This thesis presents a machine learning approach to fusing heterogeneous sensor modalities that can be systematically applied to improve sensor interpretation and reduce reliance on expertise. For the first time, echo state networks (ESNs) were used in two separate NDT and SHM data fusion case studies. The NDT-based study looked at detecting defects in steel reinforcement, teaching ESNs to combine magnetic flux leakage (MFL) and cover depth data in order to compensate for variation in MFL amplitude with increasing cover depth. Using seven different cover depths between 42.5 mm and 289 mm, the fusion approach offered improved performance for 42.5mm < depth < 205mm and the most consistent calculated optimal output threshold, demonstrating the ease of systematic application. In the SHM-based study, data from the National Physical Laboratory (NPL) footbridge monitoring project was processed by a suite of ESNs to detect, localise, classify and assess damage caused by deliberate interventions. A novel approach of combining physical and environmental sensors in order to model a different modality of physical sensor made it possible to use the residual to observe damage trends and locations, which also led to the isolation of a faulty strain gauge. There was additional success in distinguishing between different intervention types and producing a metric to express the damage level. Across both studies, the ESN approach to heterogeneous data fusion improved upon non-fusion-based alternatives. This suggests that future work should consider structures that are in regular use, combining further sensor modalities and the development of bespoke data fusion software.

Chemical sensors have gone through a lot of optimisation renaissance over the years to have come from a typical bench-top tool for measurements of ions in standard solutions, to a more promising analytical technique capable of measuring the activities of free un-complexed nutrients in environmentally and biologically important samples. With various health issues arising due to the increasing anthropogenic contributions of man to the environment amongst other factors, and due to the need for more routine analysis especially do-it-yourself (DIY) of several analytes in physiological samples for clinical purposes, it is therefore imperative that simple, cheap, but robust sensors are developed, and optimised to meet these emerging needs. First part of this work involved fabricating solid-contact ion selective electrodes (SC-ISEs) based on the mechanical abrasion of graphite on easily modified acetate paper. Similarly results from the impedance spectra and the water layer test for electrodes with or without a conducting polymer (CP) layer indicated the suitability of the procedure. The fabricated paper electrodes importantly showed fast response time and great potential stability over the course of fourteen days. The same fabrication methodology was used to produce stable and functional solid-state paper reference electrode, and then, combined with other graphite-based paper ISEs to yield a single-strip solid contact electrode for simultaneous measurements of nitrate and ammonium in environmental samples. Satisfactory results from the comparison of measured concentrations by potentiometry and standard reference methods indicated this simplified electrode platform, designed from household materials can be used as a cheaper alternative to other solid contact electrodes. Subsequent works in this thesis involved the application of the fabricated SC-ISEs in optimization of measurement procedures of environmentally important nutrients and biologically important analytes. Routine monitoring of reactive nitrogen Nr (majorly NH4+ and NO3-) in environmental samples including soils from major land types is important to soil management system. In achieving a relatively rapid turn-around time of analysis, inorganic N species were extracted from various soil types using a single extracting solution (0.1 M MgSO4). Extractable-NH4+ and -NO3- in soils, and bioavailable NH4+ and NO3- in water samples measured concurrently using paper ISEs showed similar results to standard analytical methods. The analysis of urinary iodine (UI) is important to the public health due to serious health issues attached to its deficiency. As a result, iodide-selective electrodes based on [9] Mercuracarborand-3 (MC3) and [12] Mercuracarborand-4 (MC4) as ionophores, and NPOE and DOS as plasticizers were developed with a view to evaluate the concentration of iodide in urine. However, ion-selective electrodes (ISEs) are one of the very few experimental techniques whose limit of detection (LOD) is not defined as signal-to-noise ratio. As a result, the Bayesian model was applied to estimate the activities of nitrate and ammonium in soil and water samples, and iodide in urine samples. While the Bayesian estimates for nitrate and ammonium ions were satisfactory, significant discrepancy of estimated results for iodide in urine shows more work needs to be done in relation to designing more selective ionophores to complement non-linear approaches.

The high mobility group of nucleosome binding proteins (HMGNs) are chromatin architectural proteins that bind specifically to nucleosomes and influence chromatin structure and DNA-dependent functions. However, the mechanisms underlying these events remain largely unknown. HMGN1 and HMGN2 are highly expressed by embryonic stem cells and are downregulated as differentiation proceeds. Nevertheless, embryonic and adult neural stem cells retain elevated levels of these proteins. Chromatin plasticity is essential for the pluri- and multipotency of stem cells and it is achieved by maintaining an open and dynamic chromatin conformation. Conversely, developmental potential seems to be restricted by chromatin condensation. The present work shows that loss of HMGN1 or HMGN2 in pluripotent embryonal carcinoma cells leads to increased spontaneous neuronal differentiation, which is accompanied by a reduction in pluripotency markers and higher gene expression of lineage-specific transcription factors. Inhibition of signalling pathways relevant for neurogenesis does not re-establish the phenotype observed in Hmgn2-knockout cells. Withdrawal of the factors sustaining pluripotency in embryonal carcinoma cells results in higher induction of pro-neural factors in cells lacking HMGN1 or HMGN2. Neural stem cells derived from Hmgn-knockout cells also display higher gene expression of pro-neural transcription factors and increased spontaneous neuronal differentiation. Loss of HMGN2 disrupts the active histone modification landscape, and therefore affects the chromatin structure at local and global levels. The proposition is that the local changes directly influence the transcription rates of pluripotency and lineage-specific transcription factors, while the global changes may restrict chromatin plasticity. The present data support a hypothesis whereby HMGNs contribute to the chromatin plasticity of stem cells by promoting an active histone modification landscape and open chromatin conformation, which are essential for preserving the self-renewal and developmental potential of stem cells.

Hydrogen is considered as an appealing alternative to fossil fuels in the pursuit of sustainable, secure and prosperous growth in the UK and abroad. However there exists a persisting bottleneck in the effective storage of hydrogen for mobile applications in order to facilitate a wide implementation of hydrogen fuel cells in the fossil fuel dependent transportation industry. To address this issue, new means of solid state chemical hydrogen storage are proposed in this thesis. This involves the coupling of LiH with three different organic amines: melamine, urea and dicyandiamide. In principle, thermodynamically favourable hydrogen release from these systems proceeds via the deprotonation of the protic N-H moieties by the hydridic metal hydride. Simultaneously hydrogen kinetics is expected to be enhanced over heavier hydrides by incorporating lithium ions in the proposed binary hydrogen storage systems. Whilst the concept has been successfully demonstrated by the results obtained in this work, it was observed that optimising the ball milling conditions is central in promoting hydrogen desorption in the proposed systems. The theoretical amount of 6.97 wt% by dry mass of hydrogen was released when heating a ball milled mixture of LiH and melamine (6:1 stoichiometry) to 320 °C. It was observed that ball milling introduces a disruption in the intermolecular hydrogen bonding network that exists in pristine melamine. This effect extends to a molecular level electron redistribution observed as a function of shifting IR bands. It was postulated that stable phases form during the first stages of dehydrogenation which contain the triazine skeleton. Dehydrogenation of this system yields a solid product Li2NCN, which has been rehydrogenated back to melamine via hydrolysis under weak acidic conditions. On the other hand, the LiH and urea system (4:1 stoichiometry) desorbed approximately 5.8 wt% of hydrogen, from the theoretical capacity of 8.78 wt% (dry mass), by 270 °C accompanied by undesirable ammonia and trace amount of water release. The thermal dehydrogenation proceeds via the formation of Li(HN(CO)NH2) at 104.5 °C; which then decomposes to LiOCN and unidentified phases containing C-N moieties by 230 °C. The final products are Li2NCN and Li2O (270 °C) with LiCN and Li2CO3 also detected under certain conditions. It was observed that ball milling can effectively supress ammonia formation. Furthermore results obtained from energetic ball milling experiments have indicated that the barrier to full dehydrogenation between LiH and urea is principally kinetic. Finally the dehydrogenation reaction between LiH and dicyandiamide system (4:1 stoichiometry) occurs through two distinct pathways dependent on the ball milling conditions. When ball milled at 450 RPM for 1 h, dehydrogenation proceeds alongside dicyandiamide condensation by 400 °C whilst at a slower milling speed of 400 RPM for 6h, decomposition occurs via a rapid gas desorption (H2 and NH3) at 85 °C accompanied by sample foaming. The reactant dicyandiamide can be generated by hydrolysis using the product Li2NCN.

In the current investigation the effects of higher oxygenate species on the methanol synthesis performance of various methanol synthesis catalysts were examined. Experiments were performed whereby a selected higher oxygenate (such as a carboxylic acid) was co-fed into a methanol synthesis system at low concentrations, and the results monitored by on-line GC analysis. Bulk changes in the morphology of the catalysts post reaction were investigated using XRD. Temperature programmed oxidations (TPO’s) were also performed on the catalysts post reaction to determine if carbon deposition occurred during reaction. Catalysts investigated include Rh/SiO2, Ir/SiO2, Pd/SiO2, Pd/Ca/SiO2 and an industrial methanol synthesis catalyst of a Cu/ZnO/Al2O3 formulation. The effect of the feed gas on the behaviour of the higher oxygenates were also investigated by varying the feed gas composition.

Membrane proteins are vital to drug discovery, being targeted by some 60% of the currently marketed therapeutic medicines, with more than half of those targeting transmembrane receptors. Identification of transmembrane receptor targets of poorly characterised ligands can provide new starting points for drug innovation, provide valuable information about off-target effects, and enhance mechanistic understanding of molecular pathways. Whereas, over the years, various methods for target identification have been developed, due to unfavourable characteristics, such as hydrophobicity, low abundance and transient ligand-interactions, identification of transmembrane proteins remains a challenge. Described herein is the design, synthesis and evaluation of four universal, trifunctional probes specifically developed to allow the covalent capture of transmembrane receptors in a process called ligand-based receptor capture (LRC). These probes contain three functional groups: (1) a ligand-coupling moiety; (2) a receptor-capturing moiety; (3) and an affinity tag. In an LRC experiment these probes would be coupled to the ligand of interest, after which the adduct would be added to cells believed to express the target receptor(s) to allow receptor-capturing. After affinity purification, captured receptors would be identified using mass spectrometry. All four probes contained an N-hydroxysuccinimide (NHS)-ester to allow ligand-coupling through free amines. For receptor capture, both a protected hydrazine moiety and the photoreactive groups benzophenone and diazirine were investigated. Protected hydrazine moieties will couple to aldehydes, present on sugar tails of glycosylated receptors after mild oxidation, whereas photoreactive groups will form covalent bonds with molecules in close proximity upon activation with UV-light. For affinity purification, probes either contained a biotin group, for purification using streptavidin, or an alkyne moiety, which would allow coupling to any reporter or affinity tag bearing an azide group using the copper-catalyzed azide-alkyne cycloaddition. The interactions between the two peptidic ligands, orexin A and substance P (SP), and their respective G-protein coupled receptors orexin 1 and neurokinin 1 (NK1), expressed in an inducible manner using the Flp-InTM T-RExTM system, were employed as test systems. Initially, these systems were used to investigate individual steps in the LRC protocol, including ligand-coupling, potential interference of the probes on the ligand-receptor interaction, and ability of the probes to covalently couple to the receptor. Only for the probe containing an NHS-ester, a diazirine moiety and a biotin group, could capture of the target receptor be demonstrated. This probe was then coupled to SP and used in a full LRC experiment to successfully identify NK1 as the only SP-binding receptor. This provides a proof of concept, demonstrating that this novel probe could be used as a general tool to help identify target receptors for a variety of ligands in the near future.