Chapter 1 introduces the concept of polyethylene (PE) end-functionalisation as a route to block copolymers, reviews the different literature methods for their synthesis this way, and compares the advantages and disadvantages of each. Finally, an existing method which makes use of PE terminated with a styrene derivative is identified as having fewer disadvantages than most literature procedures. Further investigation of the mechanism is proposed. Chapter 2 focusses on the different types of so-called dormant state formed in Ziegler-Natta catalysed olefin polymerisations, and in particular on the dormancy occurring after styrene insertion. Copolymerisations of ethylene with styrene, allylbenzene and 4-phenyl-1-butene in the presence of hydrogen are undertaken, and evidence for the presence of a dormant state or simply competitive rates of hydrogenation vs ethylene insertion is discussed. Increasing styrene concentration beyond that used by Chung is found to yield PE capped at both chain ends with styrene. A new mechanism – Catalytic Hydride Initiated Polymerisation (CHIP) – is consistent with these new observations. Chapter 3 focusses on extending the application of the CHIP mechanism to the synthesis of new examples of end-functional PE. Copolymerisations of ethylene with α-methylstyrene and related monomers 1,3/1,4-diisopropenylbenzene, α-methylstyrene dimer and limonene in the presence of hydrogen are investigated, resulting in the successful synthesis of a range of PE examples initiated with each comonomer. The effects of hydrogen pressure and comonomer concentration are also discussed. The advantages of CHIP are discussed, and the synthesis of end-functionalised PE incorporating DIB is studied in detail. An α-methylstyrene like end group is present at the start of the PE chains. Chapter 4 describes the free-radical copolymerisation of the new functionalised PE with acrylate monomers. Observations are consistent with a new reversible termination mechanism similar to nitroxide mediated polymerisation. The products are characterised by NMR, GPC, DLS, TEM and DSC, and the evidence is found to be consistent with the presence of block copolymers. Chapter 5 details the experimental procedures used to carry out the work in this thesis.

Metallothioneins are characterized as a group of small proteins with low molecular weight and high content of cysteinyl residues and their synthesis is induced by metal ions (e.g., Zn or Cd). The physicochemical properties of Zn-, Cd-, and Cu-containing MTs have been studied. However, copper metallothioneins (CuOMTs) have been examined less intensively, with only two MTs containing Cu(I) having been structurally characterized to date i.e., yeast MT and Neurospora crassa MT. The present study focuses on the stoichiometry and structural effects of binding of Cu(I) to the natively zinc binding MT (SmtA) from the cyanobacterium Synechococcus elongatus PCC7942. For this purpose, a Cu(I) titration study of Zn4SmtA was anaerobically performed utilizing the collective detection of ESIOMS, UV-Vis absorbance and 1H-15N NMR spectroscopy, and fully exchanged Cu(I)-SmtA was also generated from the apoOprotein. ESIOMS data confirmed the presence of predominantly monomeric Cu7SmtA. UV-vis titrations of Zn4SmtA showed that up to 7 Cu(I) displace Zn(II) from the protein, which was further studied in more detail by Cu(I) titrations of Zn4SmtA monitored with 1H-15N and 111Cd-15H NMR spectroscopy. The extensive NMR analysis showed the unfolding of protein on Cu(I) addition with absence of inertness towards Cu(I) exchange and that the protein undergoes significant conformational changes on Cu(I) addition. Preliminary characterization of MymT from Mycobacterium tuberculosis was also done and the composition of the metal cluster in the dominant Cu5MymT species was proposed and cooperativity was established by ESIOMS analyses, although structural characterisation was impeded by the highly dynamic nature of the protein.

Herein it is presented a further development of the well-established catalytic asymmetric allylation of aldehydes leading to enantiopure homoallylic alcohols Stereogenic centre(s) served as the foundation for synthesis of a variety of other advanced intermediates and building blocks with multiple chiral centres - New approaches to homoallylic alcohols were dementrated with excellent control of chiral centers - Biologically relevant carbohydrate analogues were synthesised in four possible configurations using singlet oxygen raction as the key step - δ-hydroxy-β-amino acids were synthetised diastereoselectively using Pd catalysis as the key step. - A novel approach to synthesis of isoxazolidines and pyrazolidines was demonstrated.

The halide free carbonylation of methanol is a reaction of industrial relevance. A process based upon the use of a proton-form mordenite catalyst, which cokes during reaction, is currently under investigation. This study explores the carbonaceous deposits formed upon mordenite from various methanol and dimethylcarbonate containing feedstreams. Dimethylcarbonate was investigated because it generates dimethylether upon decomposition. 13C CP MAS NMR spectroscopic studies demonstrate that the carbonaceous deposits formed over mordenite from methanol containing feedstreams contained very similar compounds (poly-methylated aromatics and polycyclic species). A combination of elemental analysis and 13C CP MAS NMR spectroscopy demonstrated that under a methanol-only feedstream for 5 minutes at 300oC, samples contained approximately 5.8 wt% carbon (which was around 45% of the 12.3 wt% observed at 300 minutes) and a distribution of species (methylated aromatics and polycyclic compounds) similar to that observed at longer times on stream (60, 180, 300 and 420 minutes). This is in contrast to the observations made after 2 minutes on stream where 3.3 wt% carbon and a relatively small amount of aromatic species were deposited. The species formed from a methanol/CO/H2 feedstream were found to be similar. Similar species were evident in coked samples generated from both dimethylcarbonate and dimethylcarbonate/CO/H2. However the carbon content for samples generated with dimethylcarbonate-only was found to be lower (9.5 wt%) for samples generated at 250oC for 300 minutes compared to those generated with methanol-only under equivalent conditions. The sample coked at 300oC displayed similar carbon contents, whereas the coked mordenite sample generated at 500oC displayed an increase in the carbon content (18.3 wt%) compared to (17.6 wt%) samples generated with methanol-only. Although similar carbon contents were observed for syn-gas containing feedstreams, the 13C CP MAS NMR studies evidenced acetic acid for samples generated at 300oC for 300 minutes with a dimethylcarbonate/CO/H2 feedstream, whereas this was not observed employing a methanol/CO/H2 feedstream at equivalent conditions. Samples generated at 250oC exhibited similar species (methylated aromatics) regardless of the presence of syn-gas. This was also true for samples generated at 500oC which exhibited polycyclic species. The sample generated at 150oC exhibited only adsorbed methanol under methanol/CO/H2, whereas under a dimethylcarbonate feedstream species indicative of methanol, dimethylether, dimethylcarbonate and zeolite bound methoxy groups were observed.

Photocatalytic processes are of widespread interest. Among different types of photocatalytic material TiO2 is the generally considered amongst the best due to its favourable physical and chemical properties. In recent decades, photovoltaic devices have been widely studied to provide alternative routes to energy and reduce dependency upon fossil fuel. Solar photovoltaic are cells capable of harvesting of sunlight into electrical power. This technology is one of the most promising routes in the search for sustainable and renewable sources of energy. The study presented in this thesis relates to the preparation and characterization of a range of different materials which can be applied in photocatalytic processes and for photovoltaic devices. The photocatalysis work has been focused mainly upon modification of the various phases of titanium dioxide. This has been undertaken via doping with nitrogen by treatment with ammonia at different temperatures. In addition, samples containing Al, Co and Cu dopants, as well as their N doped counterparts, have been prepared, characterized and tested. The photocatalytic activity was screened by following photocatalytic decomposition of an aqueous solution of methylene blue using a light source containing various components in the UV and visible regions. For selected samples, the photocatalytic activity for polymerization of methyl methacrylate and styrene has been determined with the aim of producing composites. In terms of potential photovoltaic materials, the synthesis of novel viologen compounds and polymerization via electrochemical and chemical means has been undertaken. Different viologen monomers have been synthesized with various moieties in conjugation to a phenanthroline core to afford novel push-pull systems. These compounds have incorporated both TCNE and TCNQ moieties as strong electron acceptors and hence yield chromophore with large dipole moments. In addition, novel ruthenium complexes were prepared featuring bipyridine and phenanthroline ligands. The optical and redox properties of these materials have been investigated. DSSCs have been fabricated form some of these systems and their properties have been compared to dye 719.

Fibronectin (FN) protein was discovered in the early 1970s by Richard Hynes. Since then this large, multidomain glycoprotein present in the extracellular matrix and in body fluids has been intensively research, and has been found to play a fundamental role in cell adhesion, cell migration, cell survival, angiogenesis, and other important biological processes. In recent years the interest in FN has risen; the novel FN isoform, termed Migration Stimulating Factor (MSF) has been cloned and characterized, and new results documenting the involvement of FN and MSF in wound healing, cancer progression and bacterial metastasis have been presented. The recent findings have shown that MSF’s bioactivities (e.g. stimulation of cell motility, hyaluronan synthesis and angiogenesis) are mediated by the highly conserved amino acid motif Ile-Gly-Asp (IGD), and are mimicked by small synthetic peptides containing this sequence. The aim of this project was to design and synthesize first generation non-peptidic compounds which could mimic the biological activity of MSF (i.e. IGD peptidomimetics). The second part of this thesis describes the role of FN in bacterial pathogenesis. Staphylococcus aureus is commonly present in the nose and on the skin of one third of all people, and is normally harmless at these sites. However, the microorganism possesses the ability to enter the body, invade cells and cause infection. The mechanism for S. aureus adhesion to, and invasion of, human cells has been extensively studied. It is now postulated that bacterial invasion is mediated by FN, that acts as a bridge between bacterial proteins adhesins and integrin receptors present on the cell surfaces. The biologically active motif, by which FN mediates its adhesion to bacterium, has not been unambiguously identified. However, the preliminary, unpublished studies point towards a short terapeptide sequence, Gly-Arg-Ile-Ser (GRIS), which is highly conserved within FN. We proposed to elucidate the role of the native GRIS motif by synthesising a small, nonpeptidic molecule, which could mimic its biological properties and activities.

Organic co-crystals are a class of promising materials in industries such as pharmaceuticals and energy industry. The work described in this thesis is the result of studying a series of organic co-crystals, which are synthesized by several different crystallization methods, and includes structures determined by single-crystal X-ray diffraction and powder X-ray diffraction. Chapter 1 is a general introduction to organic co-crystals and the phenomenon of polymorphism in organic crystalline materials. The importance of intermolecular interactions such as hydrogen bonding and π-π stacking interactions for the design of organic co-crystals are also highlighted. Chapter 2 describes the experimental techniques which have been used for studying organic co-crystals. These include co-crystallization methods and characterization methods such as single-crystal X-ray diffraction, powder X-ray diffraction, thermal analysis techniques and solid-state nuclear magnetic resonance. Chapter 3 reports two novel polymorphic co-crystal systems of trimesic acid (TMA) and tert-butylamine (TBA) with different stoichiometric ratios and analyses the crystal structures of the two polymorphic systems. Apart from the phenomenon of polymorphism of co-crystals of TMA and TBA, the structural diversity of other co-crystals of TMA and TBA are discussed in Chapter 4. In this chapter, all co-crystals of TMA and TBA are classified into four families based on the stoichiometric ratio between TMA and TBA, and the structural features of each family are investigated from the view point of hydrogen bonding with graph set notation. Chapters 5 and 6 demonstrate the processes of structure determination of co-crystals of TMA and ʟ-arginine (Chapter 5) and the co-crystal of pillar[5]quinone and 1,1,2,2-tetrachloroethane (Chapter 6) from powder X-ray diffraction data.

This thesis describes the application of optically active helical polymers to chiral stationary phases for high performance liquid chromatography. The use of porous graphitic carbon as a support for these phases is examined and its implication for the nature of the separation. In the first case 3,5-dimethylphenyl carbamate (CDMPC) was studied. This work continued the study by Grieb and Matlin. The use of porous graphitic carbon as a support for this polymer was examined. PGC is produced by Hypersil under the name Hypercarb. It is a porous carbon phase with virtually no surface functionalities. It was confirmed that a 25% w/w loading ofCDMPC produced using a batch coating method produced the optimum phase. The nature of the cellulose used to synthesise the CDMPC was also studied by gel permeation chromatography. It was found that Avicel cellulose (Merck) gave the best results. CDMPC has certain characteristics which make it an effective phase, these are; a) a-helical secondary structure and b) optical activity within the monomer unit. We decided to examine other polymers which possess these characteristics, in particular poly-L-Ieucine. It is believed that this polymer has an a-helical secondary structure and in its synthesis L-leucine is used as a single pure isomer. This polymer has been shown to be effective as an asymmetric organic catalyst. Poly-L-Ieucine was synthesised using condensation polymerisation with three methods of initiation using both L-Ieucine and N-carboxy anhydride L-Ieucine as monomers. N-carboxy anhydride L-Ieucine was initiated by ethylenediamine in solution and water via a humidity cabinet. L-Ieucine was polymerised using triphenyl phosphite, lithium chloride and N-methyl pyrrolidine. Poly-L-Ieucine containing a maximum of fifteen residues was synthesised using solid phase peptide synthesis techniques. These polymers were examined using MALDI-TOF and ESI mass spectrometry. The polymers synthesised from N-carboxy anhydride L-Ieucine were examined using viscometry. Comparing these results it was considered that the molecular weight of the water-initiated polymer was greater. This polymer was further modified by continuous extraction to remove lower molecular weight fragments. All of these polymers were coated onto the surface of PGC by evaporation. It was shown that a 20% w/w loading level was optimum for this type of phase. The optimum phase was found to be made from the water initiated polymer after continuous extraction. This phase was shown to be capable of the resolution ofa variety of racemic epoxides.

Single crystals of cupric acetate monohydrate dimer-d16 and potassium sulphamate-dz were studied by deuterium magnetic resonance. The theory of magnetic resonance in quadrupolar nuclei is briefly described. followed by a description of the apparatus used and the experimental technique. Several computer programs were written in Elliott ALGOL 60 for the calculation and interpretation of the results. The quadrupolar coupling constant and asymmetry parameter for the methyl group deuterons in cupric acetate' were found to be :- e2qO/h=55.6 =+. 4.Khz ﬨ = 13+.02 at 0ºC At 770K the results were unchanged. The departure of ﬨ from the expected value of zero was explained on the basis of the indirect electric field effect. After a critical .review of other work on coupling constants in C-D compounds, a value of 168 ±. 5 kHz was deduced for e2qQ/h in the static – CD3 group in cupric: acetate. Potassium Sulphamate –d2 was studied at -78°C. The results were :- e2qO/h=206.9+ 1.4 kHz, ﬨ=.14 +.01. A comparison with the results for urea showed that the magnitude and directions of the principal components of the efg tensor appeared to be controlled by hydrogen bonding.

A possible synthetic route to vitamin B12 , proposed by J. W. Cornforth, is discussed in the Introduction, which also briefly gives the present status of other synthetic routes to corrins and to vitamin B12 In Cornforth's approach, precursors of ring A and ring D of vitamin B12 are to be linked together directly by an adaptation of a bromo-nitro coupling reaction and the work described in Chapters 1, 2, 3 and 4 deals with attempts to achieve this coupling and related work. A new synthetic route to Hagemann's ester (4-carbethoxy-3 -methyl- cyclohex-2-ene-1-one), which makes available the t-butyl ester as well as the methyl and ethyl ester in improved yield, has been discovered and is discussed in Chapter 1 with some mechanistic detail. The t-butyl ester adds nitroethane (as do the other esters) in the presence of a Triton base to give a nitro -ester which can be readily hydrolysed to the nitro –acid. The nitro-ester, derived by addition of nitro ethane to ethyl-Hagemann's ester, is shown (Chapter 2) to consist of the two epimers of trans-4-carbethoxy- 3 (methyl, 2-nitroethyl)-cyclohexanone by a degradative sequence involving a Nef reaction followed by a hypobromite oxidation. The product is then related to the known trans-4-carbomethoxy-3 (methyl, carbomethoxy)- cyclohexanone. The nitro-adducts thus have the correct ring stereochemistry for further development into vitamin B12 , This degradation can also be used for correlation of the enantiomers of the nitro acid after resolution. The nitro-ethyl ester epimers are converted (Chapter 3) into a single bromo-isomer (trans-4-carbethoxy-3 (methyl, 2,2-bromonitro-ethyl)- cyclohexanone and a coupling reaction with a primary nitro-anion is described, The failure of this reaction to give coupled products leads to the protection of the ketone in the nitro -ethyl ester with an ethylene -ketal followed by conversion into a single bromo -isomer , This compound also failed in the coupling reaction. The production of a single bromo-isomer from two epimers has important implications and hence a series of acid quenching of nitroanions is studied. These show remarkable stereo selectivity and several novel mechanistic features are discussed. The stereochemistry of a possible ring D precursor had not been determined in its entirety and Chapter 4 shows how the problems can be resolved although only the initial stages have been achieved.