Very few commercial processes employ Au catalysts for the production of fine or commodity chemicals. The recent validation of Au/C catalysts to produce vinyl chloride monomer (VCM) via the acetylene hydrochlorination reaction, as a replacement of the traditionally used highly volatile and toxic mercuric chloride catalyst, represents a notable exception. However, the active form of the catalyst and the reaction mechanism are still not fully understood. The work presented in this thesis aims to provide detailed information about the nature of the catalyst's active species and the possible reaction pathway, combining commonly used characterisation techniques with more challenging in situ experiments. The first part of this thesis (Chapter 3) aims to understand the influence of the choice of solvent and metal precursor during the catalyst preparation in the activity of the final material in order to identify the active state of Au during catalysis and to propose a reaction mechanism (Chapter 3). This investigation was carried out via a in situ X-ray absorption fine structure (XAFS) spectroscopy experiment. This study led to the conclusion that under reaction conditions highly active catalysts comprise single-site cationic Au species whose activity correlates with the ratio of Au(I)/Au(III) present, providing a new insight to the structure-function relationship of this reaction, while the mechanism has been hypothesised to proceed through the oxidative addition of HCl to Au chloride, followed by the insertion of acetylene and reductive elimination of VCM. The deactivation of gold on carbon catalysts during acetylene hydrochlorination has been attributed to two possible deactivation mechanisms: the formation of oligomers on the catalyst surface blocking the active site and the reduction of active cationic gold to inactive metallic Au. These two deactivation pathways have been shown to be influenced by both reaction temperature used and the detrimental effect of acetylene rich feeds. The second part of this thesis (Chapter 4) investigates the role of each reactant on the catalyst composition to further elucidate both the reaction and deactivation mechanism via an in situ gas switching experiment while recording the XAS spectra at the Au L3-edge. This study led to the hypothesis that the oxidative addition of HCl across the Au(I) chloride species requires the concerted addition with C2H2, in partial modification of the reaction mechanism proposed in chapter 3. An inelastic neutron scattering (INS) study of the catalyst exposed to C2H2 showed the formation of oligomeric acetylene species on the catalyst surface, which, upon re-introduction of both reactants, led to significant catalyst deactivation associated with the formation of metallic Au nanoparticles. The formation of Au(0) has been directly correlated with a decrease in VCM productivity when under reaction conditions also using an higher Au loading catalys. The recently validated Au/C catalyst by Johnson Matthey, prepared by using a sulphur containing Au complex, under industrial conditions, is more active and stable than the traditional Au/C catalyst made using hard donor ligands such as Cl. Clearly the choice of the ligand plays a major role in the final activity and stability of those catalysts. Chapter 5 reports in situ ligand K-edge XAS characterisation of gold on carbon catalyst for the hydrochlorination of acetylene to understand chlorine and sulphur speciation in the catalysts under operating conditions. In both catalytic systems, Cl is bounded directly to the gold and is directly involved in the reaction mechanism, re-affirming that AuClx speciation are active site for the acetylene hydrochlorination reaction.

Members of the recently discovered family of short non-coding RNAs, termed microRNAs (miRNAs), regulate the expression of most genes encoded by the human genome by repressing translation of messenger RNAs to proteins. MiRNAs are stably expressed throughout the body and can be detected robustly and reproducibly by RT-qPCR in body fluids such as blood and urine. Alterations in circulating miRNA profiles have been associated with cancers of the brain, breast and liver, and miRNAs hold great promise as biomarkers of numerous other diseases. However, current methods for miRNA biomarker detection rely on laborious, expensive and expert techniques, and involve invasive biopsy acquisition. The research contained within this thesis focusses on the development of a non-invasive, inexpensive and rapid electrochemical analytical test to quantify miRNA in human urine samples. Therefore we describe how glassy carbon and disposable screen printed carbon electrodes (SPCEs), were modified through electropolymerisation of a naphthalene sulfonic acid derivative. DNA complementary to a target miRNA was attached and the sensor analysed via electrochemical methods using a ferri/ferrocyanide electrolyte. After hybridising with a miRNA target, this analysis was repeated and compared to the original DNA-only analysis to give a corresponding change. This was performed using buffered solutions and shown to be sensitive to 20 fM and selective against sequences with a single mismatch; urine analysis was also performed. The method was then adapted for use with screen printed electrodes, using a new chlorination solvent system, to a lowest detected concentration of 10 fM. The ink materials used for the production of the SPCEs were optimised and a new design developed to allow for multiple analyses on one sensor. A small number of diabetic kidney nephropathy (DKN) patient and healthy control urine samples were then analysed for biomarkers we have recently identified, comparing their relative expression levels.

Thapsigargin is a sesquiterpene lactone of the guaianolide class whose structure was first assigned in 1984. It is a highly cytotoxic agent, inhibiting the sarco/endoplasmic Ca2+- ATPase (SERCA) at sub-nanomolar concentrations (KD = 0.4 nM), and its prodrug formulations have been of intense interests for many oncological applications. In collaboration with the group of J.-P. Férézou, a strategy towards the construction of the carbon skeleton of thapsigargin and related natural and unnatural analogues was developed based on a ring-closing ene-yne metathesis (RCEYM) step. In this work the scope of that strategy was expanded to fulfil the enantioselectivity requirement of the synthesis via the use of asymmetric transfer hydrogenation under dynamic kinetic resolution conditions on a cyclopentenone γ-ester. These enantioenriched cyclopentenone derivatives have then been used to construct [5,7]-bicyclic structures with varying substitutions. These resulting bicyclic derivates were sensitive to many subsequent reaction conditions, however a robust synthetic strategy was found to chemoselectively oxidise the C-7/8 double bond and from there further derivation was possible, resulting in an advanced [5,7,5]-tricyclic derivative. Finally, the flexibility of the RCEYM strategy was demonstrated through the concise synthesis of an unnatural [5,8]-bicyclic thapsigargin core analogue from a common ketone precursor.

Anthropogenic emissions of volatile organic compounds (VOCs) are demonstrated detrimental to human health and environment due to their elevated toxicity and to their participation in the formation of secondary pollutants. Those pollutants contribute to the increase of the incidence of several pathologies, including respiratory diseases and cancer, which cause millions of premature deaths every year. In China VOCs pollution was demonstrated to be the primary cause of the haze episodes and elevated level of PM often reported in recent years. The catalytic oxidation process is one of the technologies available for the removal of these hazardous pollutants from contaminated gases and represents a less energy intense option to the thermal incinerator process. However, the development of more efficient and resistant catalysts is necessary to increase the applicability of this technological option. For the first time this study assessed the applicability of diatomaceous earths as support material for the preparation of transition metal based catalysts using Mn, Co, Cu and Ce as active phases by incipient wetness deposition. Different diatomites (purified and non-treated) were fully characterized and their performances towards the oxidation of benzene in CO2 and water assessed. Further analyses were carried on prepared catalysts, which were also characterized by low temperature N2 adsorption-desorption, scanning electron microscopy, X-ray diffraction, inductively coupled plasma, temperature programmed reduction and temperature programmed desorption using H2 as probe molecule to justify the results observed during the activity tests. Prepared catalysts showed elevated activity towards the oxidation of benzene at low reaction temperature, the most active catalyst (Mn10Ce10) achieving over 90% conversion of benzene at reaction temperature of 200 °C. The high activity of prepared catalysts was attributed to the low crystallinity (with particles size ranging from 10 to 50 nm diameter) and high amounts of active sites. The effect of different metal combinations was assessed and although high activity was observed for all prepared catalysts, CoxMny, MnxCey and CuxCoy resulted more effective catalysts for the removal of benzene. None of the catalysts here described achieved 100% yield of CO2 and the formation of coke was observed on all prepared catalysts. However, Mn10Ce10 and Cu4Co15 resulted stable for over 50 h reaction time showing elevated stability. Overall, this study demonstrated that diatomaceous earths might represent a suitable support material for the preparation of catalysts, and Mn10Ce10 and Cu4Co15 emerged as the most effective catalysts prepared during this study.

This thesis is mainly focused on the new technique of X-ray Birefringence Imaging (XBI). It reports applications of XBI in different research areas and also presents some developments of the fundamental theory of XBI analysis. At the end of the thesis, work on crystal structure determination directly from powder X-ray diffraction data is also included. Chapter 1 and Chapter 2 provide the theoretical background of XBI and introduce the other techniques used in this thesis. As XBI is analogous to Polarizing Optical Microscopy (POM), the introduction begins with a discussion of general optics, which is then expanded to specific case of polarized X-rays. The methodology for structure determination directly from powder X-ray diffraction data is also described. Chapter 3 demonstrates the application of XBI to study liquid crystalline materials, representing the first investigation of liquid-state samples by XBI. The experimental results show that the XBI technique is successful to elucidate the molecular orientational ordering in different liquid crystalline phases, demonstrating that characterization of molecular orientations by XBI is not limited to the solid-state. Chapter 4 explores a novel type of material – bending crystals. As an effective technique to investigate molecular orientations, XBI is shown to provide clear information on the crystal curvature. Both plastic and elastic types of bending crystal are analysed in both static and dynamic experiments. A theoretical analysis of XBI behaviour of a material containing multiple molecular orientations is also established. In Chapter 5, XBI is used to study composite organic materials. The experimental results vindicate the ability of XBI to characterize spatial distribution of molecules in composite samples. Chapter 6 reports XBI behaviour for the novel case in which two different crystals with independent orientations are present in the X-ray beam. The development of an experimental set-up for recording XBI data using a transmission-based polarization analyzer is also reported for the first time. Chapter 7 is focused on structure determination directly from powder X-ray diffraction. Three crystal structures are determined – two different urea co-crystals and one poly-aromatic compound. Chapter 8 summarises the work in this thesis, gives an appraisal of the strengths and limitations of the XBI technique, and proposes some potential research directions for the future.

This work aims to provide a detailed study of the solid Lewis acid catalyst, Sn-Beta, and particularly focuses on its use as a catalyst for biomass valorisation. Particular emphasis is put on identifying several criteria that are necessary for evaluating the feasibility of the material for intensified operation during the continuous conversion of biomass, such as stability and productivity. The catalyst is tested in continuous flow apparatus for some relevant biomass reactions, such as the valorisation of furfural, and the isomerisation of glucose to fructose. Investigation of the deactivation mechanisms is done by combining kinetic data and characterisation of the material, both fresh and used, in order to relate spectroscopic evidence to catalytic performance. The understanding of deactivation is used to develop countermeasures in order to prevent or mitigate the undesired phenomenon. Important parts of the work are also focused on material synthesis and optimisation, and combinations of different catalysts are also explored, in order to improve the overall performance of the catalytic systems studied within the work. This thesis begins with a detailed study of the effect of metal loading on the intrinsic activity of Sn-Beta (Chapter 3), where a combination of kinetic experiments and characterisation techniques are presented. This permits identification of the most suitable catalyst for continuous flow catalysis. Continuous flow experiments are then carried out in order to probe the deactivation of the catalyst. A first study of the continuous performance of Sn- Beta focuses on the model reaction of the transfer hydrogenation of cyclohexanone to cyclohexanol (Chapter 4). Following this, the transfer hydrogenation of a more complex system is studied. Particularly, the cascade conversion of furfural to 2-(butoxymethyl) furan, through tandem transfer hydrogenation and etherification over bifunctional Sn-Beta catalysts, is studied (Chapter 5). Having identified the promising stability properties of Sn-Beta during organic phase reactions, the reported “water tolerance” of Sn-Beta is then probed during the continuous isomerisation of glucose to fructose (Chapter 6). Despite showing poor levels of activity and stability in bulk water solvent, excellent continuous performance is observed when solutions of methanol containing small amounts of water (1 – 10 wt. %) are employed. In closing (Chapter 7), the consequences of the findings of this research, in addition to the pertaining challenges these findings open, are also considered.

This thesis describes the investigation of continuous flow processes that incorporate the generation and use of diazonium salts. In this manner, processes for the preparation of triazenes, indoles and acridones have been developed. Diazonium salts are potentially unstable and hazardous and have to be handled with care. The use of continuous flow processes enables the safe synthesis avoiding accumulation of large quantities. This is due to the possibility to intercept intermediates at a precise point in time within a closed system. Diazonium salts were prepared via in situ diazotization of anilines with isoamylnitrite. Triazenes were formed via the interception of diazonium salts with secondary amines. The process had to be carefully developed to avoid clogging and fouling of the reactor. 26 examples have been prepared. The thermal behavior of 13 triazenes has been compared to their corresponding tetrafluoroborate diazonium salts, which has shown they are significantly more stable. In addition, VT NMR analysis has been performed to explore restricted rotation around the triazene bond. Further developments have found that indoles can be prepared via reduction of diazonium salts to their corresponding hydrazine with ascorbic acid and subsequent Fischer indole reaction in a microwave reactor. The use of such a hybrid, machine assisted approach has enabled the formation of a library of indoles. In this manner, 33 examples have been synthesised including the drug Zolmitriptan and nine of its analogues. The formation of acridones from benzyne and anthranilates has been investigated. Benzyne was prepared via the thermal decomposition of benzenediazonium-2-carboxylate. The compound decomposes above ambient temperatures and is known to be explosive when dry. The formation of benzyne has been investigated using the Diels- Alder reaction with furan as a model reaction and then conditions were applied to a range of substrates to investigate the scope. Problems with solubility of starting materials, diazonium salts and products were encountered and partially solved through the screening of different solvents. Finally, an exothermic reaction was investigated under continuous flow reactions. Commercially available thermocouples and in line NMR analysis were used to facilitate process optimisation. The exothermic reaction explored was the reduction of TMSCF3 to TMSCF2H with NaBH4. The exotherm was monitored using external, commercially available thermocouples to realise the development of a safe reaction regime. The incorporation of in situ NMR measurements has allowed realtime assessment of reaction conversion as a correlation to the exotherm. With the combined monitoring approaches a safe scale up process has been established. A hybrid flow - batch approach was used to scale up the reaction and increase the space time yield compared to the previously reported batch reaction.

The common thread of this PhD Thesis is the use of sol-immobilised noble metal nanoparticles prepared by a novel synthetic route, where the addition of the stabilising agent has been avoided. The first part of the Thesis presents the development of a novel sol-immobilisation route without the addition of stabilisers (e.g., PVA, PVP). A monometallic 1% wt Au/TiO2 and a bimetallic 1% wt AuPd/TiO2 catalysts were prepared and extensively characterised by different techniques in order to gain information including metal loading, nanoparticles morphology and oxidation state of the metals. It has been shown that despite the stabilisers absence, is still possible to obtain materials exhibiting very similar characteristics with respect to the traditional catalysts prepared by PVA and PVP addition. The catalytic activity of the monometallic sample was firstly evaluated for the oxidation of CO (gas -phase) and glycerol (liquid-phase under basic conditions), whereas the bimetallic was employed for the solvent-free oxidation of benzyl alcohol. It has been shown that for the liquid phase reactions, samples behave in a very similar manner to the traditional ones. However, the stabiliser-free catalyst was not active as expected for CO oxidation: reasons for this behaviour might be related to the nanoparticles size or to the presence of poisonin g species (i.e., chloride) on the catalyst’s surface. The second part is focused on the study of glycerol oxidation in basic conditions by using the novel mono and bimetallic catalysts synthesized stabiliser-free and their comparison in terms of activity and selectivity to the traditional catalysts synthesized by common stabilising agents PVA and PVP. It has been shown on the first instance that the selectivity towards the main products tartronate and glycerate follows a trend depending on the presence and nature of the stabiliser, with the stabiliser-free samples being more selective towards the former, followed by PVA and PVP. Experiments at short time and using glyceric acid as starting material revealed that the tartronate cannot only arise as product of secondary oxidation of glycerate. Finally, experiments where selected aliquots of PVA and PVP were added during reaction showed that the nature of the polymer affects the conversion and selectivity. However, the mechanisms involved have not been fully understood yet. The third part presents the catalytic activity of a series of Au and AuPd sol-immobilised catalysts for the plasmonic oxidation of glycerol under neutral conditions. It has been shown tha t the catalysts prepared by sol-immobilisation are active under plasmonic conditions. The effect of the presence and nature of the stabilising polymer, the wavelength and time of illumination and of calcination have also been investigated. The catalytic activity was proven to be related to the plasmonic effect by performing reactions using different wavelengths of illumination; the nature of the polymer was proven to affect the plasmonic response of the catalyst; stabiliser-free samples activity significantly improved after calcination, likely due to a stro nger nanoparticle/support interaction. The plasmonic effect has also been observed for a series of 1% wt AuPd/TiO2 catalysts prepared with different Au:Pd ratios, with enhancement in the conversion increasing with the increase in the gold content.

Bax peptide 1c (FLIMGWTLD) and two of its derivatives, 15-mer cyclic peptide 2c (FLRELIRTIMGWTLD), 13-mer cyclic peptide 3c (FLKSSKIMGWTLD) with their linear counterparts (1b, 2b, 3b) were prepared by a head−to−tail cyclisation strategy, purified (HPLC), characterised and identified (LCMS). Then the mass and concentration of the two derivatives (2c, 3c) with their linear counterparts (2b, 3b) were calculated. MS2 mass spectra were used as evidence of synthesis of the cyclic peptides from their linear counterparts. There was a clear difference between each of the two cyclic peptides and its linear counterpart’s mass spectra. A peak appeared for a fragment which has the two termini bonded together (Phe−Asp) in the cyclic peptide spectrum (1c, 2c, 3c) that did not appear in the linear peptide spectrum (1b, 2b, 3b). The enzymatic degradation and kinetic study were undertaken for just the two derivatives (2c, 3c) with their linear counterparts (2b, 3b) using trypsin and chymotrypsin. Compound 1c and its linear counterpart (1b) were excluded from these two studies and the stability studies of the peptide in fetal calf serum (FCS) medium because the 9-mer cyclic peptide (1c) had very low solubility in HPLC solvents and was hydrolysed during storage in the freezer. Chymotrypsin cleaved the peptide bond between Trp and Thr but did not cleave the peptide bond between Phe and Asp in the 15-mer cyclic peptide (2c) and its linear counterpart (2b). Cyclisation of the linear peptide (2b) did not improve the stability of the peptide as the t1⁄2 of the cyclic peptide (2c) was less than the t1⁄2 of its linear counterpart (2b). Trypsin cleaved the peptide bond between Arg and Thr in the linear peptide (2b), while in the cyclic peptide (2c) the cleavage was between Arg and Thr in addition to Arg and Glu. Stability of the cyclic peptide (2c) did not improve significantly as the t1⁄2 of compound 2c increased slightly in comparison to the t1⁄2 of its linear counterpart (2b). The effect of chymotrypsin on the two peptides (3b, 3c) was the same. The peptide bond between Trp and Thr was hydrolysed in the two compounds (3b, 3c), while between Phe and Leu did not break. Cyclisation of the linear peptide (3b) did not improve the stability of the peptide because the t1⁄2 of the cyclic peptide (3c) increased slightly in comparison to the t1⁄2 of its linear counterpart (3b). There was significant stability for the cyclic peptide (3c) against trypsin in comparison to its linear counterpart (3b). Compound 3c did not hydrolyse for 30 min, while compound 3b was hydrolysed at the peptide bond between Lys and Ile in the first few minutes of the enzymatic hydrolysis. The stability of 15-mer cyclic compound (2c) was less than its linear counterpart (2b) in the medium of fetal calf serum (FCS) as the t1⁄2 of compound 2c (120 h) was less than the t1⁄2 of compound 2b (165 h). In contrast, the stability of the 13-mer cyclic compound (3c) was more than its linear counterpart (3b) as indicated by the t1⁄2 of compound 3c (285 h) that was more than the t1⁄2 of 3b (110 h).

This thesis describes the preparation and characterisation of graphene-derived composites with ammonia borane or metal borohydride-based materials as a hydrogen store. Ammonia borane and light metal borohydrides can be seen as attractive candidates for hydrogen storage due to their relatively high hydrogen gravimetric and volumetric densities. The development of renewable energies is nowadays a necessity and hydrogen is seen as a promising alternative to fossil fuels. This thesis work was motivated by the intensive need for high-performing solid-state hydrogen stores and by an interest in assessing the potential of graphene-derived materials to fulfil such objectives. In this study, we describe a fresh approach to nanocomposite fabrication, first designing a novel porous host material from (partially reduced) graphene oxide ((r)GO) and subsequently engineering nanocomposites with the hydrogen store in a simple one-step process. New 3-dimensional porous scaffold materials have been fabricated by ice-templating sheets of graphene oxide (GO) or partially reduced graphene oxide (rGO). Aqueous suspensions of GO (or rGO) can be cast into monoliths or formed as beads on cooling and the solid matrices can be fashioned with either laminar or radial porosity as result. GO beads with radial lamellar porosity and typical diameters of ~ 2.8 mm and densities of ~ 8 mg.cm-3 were obtained. Further, ammonia borane (AB), itself with a gravimetric capacity of 19.6 wt.% hydrogen (ca. 13 wt.% at more workable dehydrogenation temperatures), can be integrated into the hierarchical structures in-situ in a one-step process without the requirement of melt infiltration or solution impregnation techniques. The ensuing self-assembled beads release hydrogen without volume expansion on heating, supressing the release of diborane and borazine, and significantly decreasing the ammonia release. The use of partially reduced graphene oxide (rGO) as a scaffold also demonstrated the elimination of CO/CO2 release from the carbonaceous matrix. Thermal analysis confirms that both the kinetics and thermodynamics of AB dehydrogenation are altered by its incorporation in the nanocomposites and shows improved dehydrogenation properties compared to that of neat AB. Metal borohydrides such as lithium borohydride LiBH4 (18.54 wt.% hydrogen), magnesium borohydride Mg(BH4)2 and its ammoniated equivalent Mg(BH4)2.6NH3 (respectively 14.96 wt.% and 16.8 wt.% hydrogen theoretical content) were also investigated. Nanocomposite formation occurs in-situ and requires no subsequent impregnation or infiltration step. Self-assembly is again driven by the growth of “ice” crystals during the templating process. The dehydrogenation temperature was significantly decreased, with for example an onset of ca. 70 °C for the magnesium-based systems. More than 5 wt.% hydrogen desorption was measured for the rGO-Mg(BH4)2.6NH3 composites on heating from 30 – 350 °C under flowing argon, with higher hydrogen purity than Mg(BH4)2.6NH3 itself. All systems were characterised principally by Powder X-ray diffraction (PXRD), Infrared and Raman spectroscopy, and electron microscopy to obtain information related to the sample structure, composition, and morphology. Simultaneous thermogravimetric analysis (TG-DTA) coupled with mass spectroscopy (MS) was also performed in order to investigate the thermal decomposition of the materials allowing an assessment of their onset and peak hydrogen release temperatures, the gravimetric hydrogen density, and the nature and amount of the gases evolved during the decomposition.