Room temperature iodocyclisation of homoallylamines stereoselectively delivers functionalised 2- (iodomethyl)azetidine derivatives in high yield. Increasing reaction temperature from 20 °C to 50 °C switches the reaction outcome to realise the stereoselective formation of functionalised 3-iodopyrrolidine derivatives. It was shown that these pyrrolidines are formed via thermal isomerisation of the aforementioned azetidines. Primary and secondary amines could be reacted with iodomethyl azetidine derivatives to deliver stable methylamino azetidine derivatives. With subtle changes to the reaction sequences homoallyl amines could be stereoselectively converted to either cis- or trans- substituted 3-amino pyrrolidine derivatives at will. The stereochemical divergent synthesis of cis and trans substituted pyrrolidines supports an ion part, aziridinium, isomerisation pathway for azetidine to pyrrolidine isomerisation. Six azetidine derivative were probed in a zebrafish embryo developmental assay for capacity to illicit morphological changes. The range of effects across the probed molecules demonstrates the suitability of this assay for screening azetidine derivatives. One of the probed molecules, rac-(((cis)-1-benzyl-4-phenylazetidin-2-yl)methyl)piperidine, exhibited particularly promising effects in the developmental assay.

At the elevated temperatures required for metal carbide synthesis, atomic diffusion across particle boundaries can occur, resulting in the fusion of smaller particles into larger ones. This process is termed sintering. By providing a physical barrier for the inhibition of sintering, in the form of easily removable alkaline earth metal oxide “cast materials”, this thesis shows that Prussian Blue nanoparticles can undergo thermal decomposition to produce discrete Fe3C nanoparticles. The overarching aim of this work is to push the boundaries of metal carbide synthesis by forming the basis of a technique that can eventually be applied to the synthesis of a wide range of discrete metal carbide nanostructures. A combination of energy dispersive X-ray analysis and electron tomography provides evidence of efficient dispersal of Fe3C nanoparticles throughout various cast materials and ample evidence of < 100 nm Fe3C particle diameters. Scanning electron microscopy provides evidence of the ability to disperse these particles over a catalyst support, and superconducting quantum interference device measurements show superparamagnetic behaviour for the Fe3C particles. The technique is then extended to larger size regimes in the biotemplating of carbonised microcoils using the algae species spirulina.

The aim of this project was to prepare novel ferrocene-based Hydrogen-bonding receptors and to study them in the electrochemical sensing of neutral compounds and in organocatalysed transformations. The synthesis and characterisation of 2-ferrocenyl oxazoles via gold chemistry to access a new H-bonding motif for electrochemical sensing was successfully achieved. However the targeted structure bearing a secondary amine at the 4-position of the oxazole, was found to be highly unstable and unsuitable for sensing applications. Further studies on ferrocene-based H-bonding systems towards their application in asymmetric organocatalysis were also carried out. Different chiral and achiral ferrocene-(thio)ureas were prepared and tested in four organic reactions. Their performances in the Henry and in the Morita-Baylis-Hillman reactions gave acceptable yields but did not show significant enantioselectivities. A bi-functional ferrocene-thiourea was found to be effective in the enamine co-catalysed aldol reaction of acetone and \(trans-β\)-nitrostyrene, and in the double Michael cycloaddition of ω-nitropentenoate methyl and \(trans-β\)-nitrostyrene, leading to a tetrasubstituted cyclopentane. The H-bonding properties of the ferrocene-(thio)ureas with carboxylates was also studied by \(^1\)H NMR spectroscopy. Finally, approaches towards the preparation of ferrocene-based boronate-ureas were investigated.

Chirality, familiar to all chemists, is usually applied to molecules or assemblies of molecules and plays an important role in both animate and inanimate systems. It is commonly the case that chirality of a system arises from a chiral building block yet chiral systems can also emerge from achiral units. The objective of this research was to investigate the origin and recognition of chirality at the nanoscale level. To do this, self assembled monolayers made of chirally and achirally tailed molecules were used because such structures are known to form uniform surfaces, which can act as either a source of nucleation or the probing surfaces in chiral recognition. The strategy adopted in the first part of this study was to use chirally modified self assembled monolayers as a source of nucleation for crystallization of achiral compounds that can form either left or right tended forms in chiral crystallization. Such compounds, widely reviewed by Matsura, form chiral crystals even though their building blocks lack a chiral centre. This study presents experiments of induction of chirality in sodium chlorate, hippuric acid and 2,6-ditertbutyl-4-methylphenol crystals. Chiral crystallization of chosen compounds was conducted on D and L cysteine surfaces assembled on gold. The chirality of crystals grown on these surfaces was determined using polarised light microscopy, circular dichroism spectroscopy and NSOM. The small enantiomeric excess achieved in experiments was explained by the limits of chirality determination methods. It was found that crystals formed in enantiomeric excess were of opposite chirality to the SAM they were grown on. This confirms previous results presented by Mastai on crystallization of histidine on cysteine surfaces. The second part of this study presents studies of chiral recognition use of AFM technique-Force Distance Spectroscopy. Chirally and achirally modified SAMs were formed via the Cu-AAC reaction commonly called 'click Chemistry'. This project investigated how the surface preparation influences chiral recognition and if the presence of the second chiral centre affects probing ability. For surface preparation, three types of linkers were used. To functionalize them two complementary compounds equipped with AlaAlaDL and AlaAlaLL dipeptide tail were used. Additional studies were carried out with hippuric acid and glutamic acid-modified SAMs. These studies showed that the way the surface is prepared plays an important role in chiral recognition. In the final recognition experiments it was found that use of molecules possessing either peptide groups or amino acid groups generates additional forces between interacting surfaces, which can be equilibrated by conducting measurements in pH close to their isoelectric point. An influence of the second chiral centre was found for the loosely packed surfaces where the molecules can freely coil.

The direct cyclisation between alkynes and ketones was described by Conia in 1964. Under high temperatures (150-650 °C), alkynyl and alkenyl ketones were converted into carbocycles, bis-fused carbocycles and spiro compounds by a pericyclic ene-type reaction. However, the use of elevated temperatures limits its applications to thermally robust molecules. Since the original report, a significant amount of effort has been made to develop alternative approaches under mild conditions. These methods employ activated methylenes, frozen enol equivalents or enamine intermediates as nucleophiles in the presence of a Lewis acid (Hg, W, Pt, Au) to activate the unsaturated moiety. Although, synthetically useful, these processes are limited by the necessity to use a preformed enol or a co-catalyst, which involves additional synthetic steps and reagents.

In this thesis the work presented focused on the doping of oxyanions, borate, silicate, sulfate and phosphate, into different materials with the perovskite structure for use as electrolytes or cathodes in solid oxide fuel cells. Phosphate and sulfate doping was shown to have been carried out successfully on gallium doped barium and strontium scandates. They all adopted the cubic perovskite structures with the presence of oxyanions confirmed by Raman spectroscopy. These samples were found to have improved stability to CO2 atmospheres with increasing gallium content. Phosphate doping was also carried out on doped barium cerates and was found to lower the conductivity while not leading to improved stability. Oxyanion doped barium stannates were investigated and showed a lower conductivity on oxyanion doping and borate doped samples showed an improved stability in reducing atmospheres. Following on from earlier work on silicate doping in perovskite cathode materials silicon doping was carried out on (Ca/Sr)2MnFe1-xSixO6-δ which resulted in the formation of cubic perovskites with a mixed oxidation state on the B site. Conductivity and area specific resistance data were collected for the samples showing an initial improvement on silicon doping for two of the series.

New techniques for rapid identification of complex mixtures of viral and bacterial DNA and for visualising multi-copy plasmids in single bacterial cells have been developed using a combination of methyltransferase-directed labelling, molecular combing, and widefield microscopy. In Chapter 2 the protocol for methyltransferase-directed labelling was optimised. A maximum labelling efficiency of 50% (as measured by single molecule counting results) was obtained for Atto 647N-labelled pUC19. In Chapters 3 and 4 the optimised labelling protocol was used to label genomic DNA for optical mapping and identification. The in silico results in Chapter 3 show that the combination of techniques used in this thesis represents the ‘sweet-spot’ for optical mapping and identification of microorganisms. In Chapter 4 this combination of techniques was used along with a new algorithm, for rapid identification of bacteriophages, Adenovirus A, resistance plasmids and bacterial strains in complex mixtures of genomic DNA. Finally, Chapter 5 uses methyltransferase-directed labelling to investigate the mechanisms bacteria use to maintain and transfer resistance plasmids. Atto647N-labelled pUC19 and pRSET B plasmids were visualised in E. coli bacteria and diffusion over several seconds or plasmid segregation over many hours was studied.

The spread of the tuberculosis (TB) has been further accelerated by the emergence of multi- and extensively-drug resistant Mycobacterium tuberculosis strains, thereby further increasing the need to characterise novel drug targets and develop anti-TB agents. The cell wall of M. tuberculosis plays a key role in survival of the pathogen in the host cell, making it an attractive drug target. The findings in this thesis present three different studies that contribute to the discovery of novel drug targets. Using a whole-cell screening approach and the generation of spontaneous drug-resistant mutants in M. smegmatis, a surrogate model of M. tuberculosis, we identified a new inhibitor which targets glycerol metabolism. The two remaining studies involved studying the biosynthetic pathways of critical cell-wall components. In this first study, Conditional expression specialised transduction essentiality test was used to confirm the essentiality of MSMEG3859 in M. smegmatis, an enzyme which generates mannose donors that are utilised in the biosynthesis of higher order Phosphatidyl-myo-inositol mannosides, Lipomannan (LM) and Lipoarabinomannan (LAM), important immunomodulators in mycobacteria. Furthermore, a deletion mutant of Protein kinase H (PknH) in M. tuberculosis was used to demonstrate its importance in the production of LM/LAM and Phthiocerol dimycoserosates, a glycolipid that is also involved in TB pathogenesis. Thus, both Ppm1 and PknH can potentially be used as future therapeutic targets against M. tuberculosis.

The brown alga, Dictyota dichotoma, collected from the Indian Ocean has proven to be a prolific source of new diterpenes. The diterpene, dictyoxetane, isolated from the brown alga, is structurally related to the dollabellane class of natural products. Dictyoxetane is the only known natural product having the 2,7-dioxatricyclo[4.2.1.0]nonane ring subunit. Chapter 1 of this thesis describes the isolation, structure and proposed biosynthesis of dictyoxetane. The methods reported in the literature for the preparation of the dioxatricyclic framework are discussed, which might be applied in a synthesis of dictyoxetane. The Grainger group has previously reported the synthesis of the trans-hydrindane core of dictyoxetane starting from a Robinson annulation-derived bicyclic enone. Asymmetric approaches to the starting hydrindanone in this synthesis and the Hajos-Parrish ketone are also presented. Chapter 2 reports the efforts to address the current limitations of this approach, namely the low-yielding Robinson annulation of an expensive starting material, 2-methylcyclopentanone. An asymmetric synthesis of the trans-hydrindane ring system starting from the Hajos-Parrish ketone, involving chemoselective radical-based deoxygenation, is reported. Studies towards dioxatricyclic ring annulation are described in Chapter 3. A number of strategies such as radical cyclisation, ring-expansion and [4+3] cycloaddition are investigated towards 7-membered ring formation. The Lee [5+2] annulation using allylsilane acetals and olefin metathesis both provided a way to annulate a 7-membered ring to the hydrindanone system en route to dictyoxetane.

Two separate experimental techniques have been used to investigate the fundamental properties of small polyatomic molecules in the gas phase. Selected ion flow tube mass spectrometry has been used to study the reactions of cations and anions with ethene, monofluoroethene, 1,1-difluoroethene, trifluoroethene and tetrafluoroethene. Calculated collisional reaction rate coefficients are compared to those measured by the experiment. The product ions from these reactions have been detected and their branching ratios measured. Many of these results have been explained using arrow-pushing mechanisms. Using tunable vacuum-ultraviolet radiation from a synchrotron, negative ions have been detected following photoexcitation of 24 gaseous molecules. The majority of the molecules studied are halogen-substituted methanes. Product anions resulting from unimolecular ion-pair dissociation reactions were detected, and their ion yields recorded in the range 8-35 eV. Absolute cross sections for ion-pair formation and resulting quantum yields are calculated. This vast collection of data is summarised and ion-pair formation from polyatomic molecules is reviewed.