The aim of this work was to assess the viability and limitations of certain reactions of the tetracarbony1coba1tate (1-) anion with organic halides as steps in some synthetic pathways. Primarily, the work was concerned with attempts to extend the formation of dia1kyl ketones from alkyl halides and carbon monoxide to the formation of cyclic ketones from a,w-dihalides and carbon monoxide.

Synthetic targets that mimic key structural and conformational features in proteins are of intense scientific interest. These structures can reproduce the biological activity of their naturally occurring counterparts, while improving their properties in vivo. This project focuses on the synthesis of beta-turn mimetic structures, based on the opioid pentapeptide leu‑enkephalin. More specifically, the target mimetics in this project are based on the enkephalin derivative, leu‑enkephalinamide. Leu-enkephalin is conformationally very flexible, giving it the ability to bind to different opioid receptors. This results not only in the physiological relief of pain, but also in various potential side effects such as miosis or physical dependency. Natural peptide structures also have limited suitability for drug applications because of their poor transport properties and their tendency to undergo proteolytic degradation. The synthesis of macrocyclic mimetics can overcome these problems and give a conformationally rigid molecule that exhibits a desired biological activity. This thesis will discuss some published examples of beta-turn mimetic structures that have been designed and synthesised by research groups working in this field. The examples that are shown have been chosen to illustrate some of the work that has taken place in this area over recent years. Advances in the synthesis of ynamides and other ynamine analogues is also discussed, due to the importance of this type of chemistry in the research project. Efforts towards the synthesis of several 10-membered macrocycles are described herein. The target structures are model compounds that are designed to explore varied chemical approaches towards such ring systems. This thesis will discuss the synthesis of several linear precursors to the proposed macrocycles and efforts to cyclise these structures to form the desired targets. The targets that were synthesized employed varied approaches to the key cyclisation reaction. Initially, a metal-mediated coupling approach to an ynamide target was chosen. This was subsequently refined by including a proline residue in the linear precursor to bring the reacting groups into closer proximity. Finally, several approaches were investigated to close an alkyne bonded macrocycle by coupling the amide functionality at the opposite side of the ring.

Spirocyclic piperidines and spirocyclic pyrans are prevalent throughout nature, often appearing in natural products which exhibit exciting biological activities. Notable examples of spirocyclic piperidine-containing biologically active natural products are halichlorine, pinnaic acid and tauropinnaic acid. Despite their structural similarity, halichlorine and the pinnaic acids were isolated from separate organisms; halichlorine was isolated from extracts of the marine sponge Halichondria okadai while both pinnaic acid and tauropinnaic acid were isolated from the Okinawan bivalve mollusc Pinna muricata. The complex hybrid molecule polymaxenolide contains a representative spirocyclic pyran core. The biological profile of polymaxenolide is not yet known, however its hybrid origins have rendered it a target of significant interest. The work described herein details the development of a methodology capable of accessing both spirocyclic pyran and spirocyclic piperidine core structures from a common cyclic tertiary furfuryl alcohol intermediate. The key spirocycle forming step involves the oxidative rearrangement of cyclic tertiary furfuryl alcohols and amines for the synthesis of spirocyclic pyrans and piperidines, respectively. Efforts towards the synthesis of a complex, africanane-derived Southern fragment, with the intention of applying this methodology towards the synthesis of polymaxenolide are reported. This methodology has been further elaborated to complete an asymmetric synthesis of the upper framework of an oxa-analogue of pinnaic acid. The potential for a spectator protecting group free synthesis of pinnaic acid was also explored and the synthesis of an advanced intermediate is also reported.

The detailed study of the structure and electron density distributions of polymorphic and phase transition materials is presented. Understanding and predicting the appearance of polymorphism and phase transitions in organic and organometallic materials is of considerable interest in fields such as pharmaceutical science, solid-state chemistry, and materials science. However, the small lattice energy difference between the different molecular conformations and packing between these materials are often particularly challenging in this area. Consequently, obtaining the most accurate description of the atomic positions and the electronic distributions plays an extremely important role in obtaining the best estimation of the lattice energies. In the present work,high-resolution X-ray diffraction as well as neutron diffraction tehniques have been used in reaching these aims. For minimizing the data collection times, synchrotron sources were also used for obtaining X-ray diffraction data, including Diamond, I19 beam line and Soleil, CRYSTAL beam line. Molecular complexes of lutidine isomers and chloranilic acid are also studied, in both 1:1 and 2:1 ratios, in order to investigate their relative stabilities through hydrogen bond contributions towards stabilising stoichiometrically different ‘compositional polymorphs’. The energy stability rankings in small organic molecules and transition metal complexes which exhibit polymorphism or displacive phase transitions are calculated using experimental charge density and fully theoretical approaches. The effect of the hydrogen bonds in the rank stabilities is also investigated. The pharmaceutical sulfathiazole and piracetam compounds are identified to have very small lattice energy differences between the polymorphs studied and the ranking stability orders are not maintained in the approaches used. Studies of the coordination complex [Ni(en)3]2+(NO3-)2 show that, contrary to expectation, the higher temperature phase is calculated to be the most stable one, showing the strongest intermolecular interaction energies. Overall, the presented studies show that current methodologies for estimating solid state lattice energies, even using high quality diffraction data and complex modeling of the electron density, are not sufficiently accurate to allow reliable estimation of polymorph energy differences. The results obtained for all studied polymorphic and phase transition materials using the experimental charge density approach show a high dependence of the lattice energies on the multipole model used.

This research deals with the investigation of the correlation between the structures of molecules and their magnetic properties as a function of pressure. To do so, different kinds of molecules have been chosen from single-molecules magnets, chains to small molecules. The variety of molecules is necessary to find the best candidates for high pressure X-ray crystallography and high pressure magnetic measurements. Bonds lengths and angles have been successfully altered by using high pressure without the complicating issues of chemical modifications. These structural changes produced a significant effect on the magnetic properties. A tilting of the Jahn-Teller axis in [Mn12O12(O2CCH2tBu)16(H2O)4].MeNO2.CH2Cl2 has been observed both structurally and magnetically. Modification of π–π interactions from edge to edge interaction to offset π–π stacking in [Gd(PhCOO)3(DMF)]n or a conversion from a CH–π interaction to a π–π interaction in [N(PhCH2)(CH2CH3)3]2[Fe2OCl6] are also reported.

The first study was looking into the phytochemical analysis of herbal medicinal plant from Malaysia. Phenolic compounds in an aqueous infusion from leaves of Ficus deltoidea (Moraceae), a well-known herbal tea in Malaysia, were analysed by HPLC coupled to photodiode-array and fluorescence detectors and an electrospray ionization tandem mass spectrometer. Following chromatography of extracts on a reverse phase C12 column 25 flavonoids were characterized and/or tentatively identified, with the main constituents being flavan-3-ol monomers, proanthocyanidins and C-linked flavone glycosides. The proanthocyanidins were dimers and trimers comprising (epi)catechin and (epi)afzelechin units. No higher molecular weight proanthocyanidin polymers were detected. The antioxidant activity of F. deltoidea extract was analysed using HPLC with on-line antioxidant detection. This revealed that 85% of the total antioxidant activity of the aqueous F. deltoidea infusion was attributable to the flavan-3-ol monomers and the proanthocyanidins In terms of the bioavailability of hydroxycinnamates with the high occurrence of p-coumaroylquinic acid in F. deltoidea extract, further study was carried out using radiolabeled caffeic acid. In the study, male Sprague-Dawley rats ingested 140 x 106 dpm of [3-14C]trans-caffeic acid and over the ensuing 72 h period body tissues, plasma, urine and faeces were collected and the overall levels of radioactivity determined. Where sufficient radioactivity had accumulated samples were analysed by HPLC with on-line radioactivity and tandem mass spectrometric detection. Nine labeled compounds were identified, the substrate and its cis isomer, 3¢-O- and 4¢-O-sulphates and glucuronides of caffeic acid, 4¢-O-sulphates and glucuronides of ferulic acid and isoferulic acid-4¢-O-sulphate. Four unidentified metabolites were also detected. After passing down the gastrointestinal tract the majority of the radiolabeled metabolites were excreted in urine with minimal accumulation in plasma. Only relatively small amounts of unidentified 14C-labeled metabolites were expelled in faeces. There was little or no accumulation of radioactivity in body tissues, including the brain. The overall recovery of radioactivity 72 h after ingestion of [3-14C]caffeic acid was ~80% of intake. The role of colonic microflora in the metabolism of caffeic acid was carried using an in vitro model of the human colonic microflora. Caffeic acid (55 µmoles) was incubated with human faecal materials obtained from five Asian donors, and caffeic acid degradation was monitored from 0-8 h. Faecal samples were analysed by GC-MS, where major phenolic acids identified were dihydrocaffeic acid, 3-(3¢-hydroxyphenyl)propionic acid and phenylacetic acid. Caffeic acid was quickly degraded by the colonic microflora, as it disappeared after 4 h of incubation in two of the faecal samples. The degree of degradation of caffeic acid was significantly influenced by the addition of glucose as well as individual variations in the density and the composition of microflora. These findings support extensive metabolism of caffeic acid in the colon, depending on the substrate concentration and the supplement of glucose which resulting the formation of simple phenolics.

This thesis details the physical and electronic structure of several technologically important transition metal chalcogenides (TMCs) using a combination of transmission electron microscopy (TEM) and surface science experimental techniques. The materials studied include CuxTe and CdTe, which find application in high efficiency, low weight photovoltaic devices. CuxTe alloys are frequently used as an electrical back contact in high efficiency CdTe photovoltaics. Here, we examine the alloying of Te on the Cu(111), polycrystalline Cu and Cu(643) surfaces. Chapter 3 of this thesis shows that the alloying of Te and Cu(111) is facile at room temperature, contrary to previous reports. Two distinct surface phases exist, depending on Te surface concentration. Below a coverage of 0.33 monolayers (MLs) of Te a surface substitutional alloy (SSA) is found to exist, where a Te adatom substituted for a surface Cu atom. For Te coverages greater than 0.66 ML, an unusual Cu3Te2 alloy continually grows on the surface, stabilised by a good lattice match to the Cu(111) substrate. The surface alloying of the Cu-Te system displays an intriguing dependence on the surface termination of the Cu substrate. Of the three Cu substrates studied here, Cu(111), Cu(643)R and polycrystalline Cu, a 1 ML film of Te gave ordered alloy structures with stoichiometries of Cu3Te2, CuTe and Cu2Te, respectively. In chapter 4, the study of thin film photovoltaics is extended to the deposition of CdTe onto Cu and CuxTe substrates. CdTe is observed to grow three dimensionally on Cu(111), Cu3Te2 and Cu2Te. Cu+ diffusion, crucial for photovoltaic performance, is detected for CdTe thicknesses greater than 2 ML and is assigned, predominately, to Cu2Te crystallites forming within the CdTe layer, with a minor amount of Cu residing in interstitial sites in the host CdTe structure. Chapter 5 describes the alloying of Te with a intrinsically chiral surface, Cu(643)R, the first study of its kind. The results of this study reveal that step mediated alloying occurs between Cu and Te with significant faceting of the surface. Two ordered CuTe alloy phases were observed for sub-monolayer Te coverages. The low coverage alloy exists for Te coverages between 0.18 ML and 0.45 ML and has a chiral unit cell. The high coverage alloy exists for Te coverages between 0.45 ML and 1.5 ML and has an achiral unit cell. The atomic positions of these surface alloys are tentatively interpreted from the scanning tunnelling microscopy (STM) images. In contrast to the thin film experiments in chapters 3-5, chapter 6 describes a study of TaS3 nanoribbons. These studies reveal that the nanoribbons have a distinct core-shell type structure. Characterisation with surface science techniques shows that the shell is nonstoichiometric and amorphous while TEM shows a crystalline core to the material. Interestingly, the TaS3 are observed to be unstable when interfaced on a Au substrate, with the shell persistently losing S to the substrate, which have potential implications in device integration.

Cornexistin and hydroxycornexistin were both isolated from the fungus Paecilomyces variotii. They were found to possess significant herbicidal activity, which triggered the interest of agrochemicals companies. Their structures consist of a nine-membered carbocyclic ring fused to a cyclic anhydride with various oxygen functionalities decorating the nine-membered core. Previously, the synthesis of (±)-5-epi-hydroxycornexistin was successfully achieved in the group, using a Stille-coupling reaction between a chloride and stannane fragments, followed by a key ring-closing metathesis reaction to form the core of the ninemembered ring. However, the desired stereochemistry on the C-5 centre could not be installed despite the use of a variety of methods. A new strategy, involving an intramolecular Nozaki-Hiyama-Kishi reaction was investigated, leading to the formation of an advanced intermediate for the synthesis of hydroxycornexistin. The reaction proved efficient and X-ray crystallography was used to confirm the desired formation of the natural C-5 configuration of cornexistins. The stereoselectivity of the reaction was considered and alternative methods to improve the diastereoisomeric ratio were attempted. The asymmetric synthesis of hydroxycornexistin was studied, using an advanced model substrate and an efficient strategy for the asymmetric syntheses of both Stille-coupling partners was performed. The synthesis of the chloride fragment involved a crossmetathesis reaction and a [3,3]-sigmatropic rearrangement reaction as main steps of the reaction sequence. Using a chiral auxiliary, the stannane fragment was obtained with excellent enantiomeric excess. Finally, the sequence leading to the synthesis of the NHK precursor was accomplished.

The availability of surplus capital from the oil producing Arab Gulf States has allowed joint ventures to become an economic reality and important Arab World phenomenon. Using appropriate methodology, projections have been made of population growth, petrochemical production levels and per capita income with a view to determining the market for textiles in the Arab States. Shirt production has been chosen as an area for the pilot development of projects based on textiles. Factors influencing the choice include the relatively small capital requirement, the use of sophisticated technology in a labour intensive industry, the possible diversions into similar areas and the use of raw materials produced in the Arab World. The project envisages the creation of an inter-Arab joint venture between Kuwait, the provider of capital, and Morocco, the production base. A computer model has been designed to produce one million shirts of various types per annum. The model embraces cash flows, rates of erage utilised capacity. The model allows a variety of different situations to be analysed In terms of varying input parameters. The flexibility is such that it may be made the basis for many similarly oriented projects. Constraints were identified - particularly those associated with obtaining Venture Capital. The problem of regional enterprise development within the Pan-Arab World was examined, and past lack of success of such enterprises identified with over idealistic objectives.

Organic chemistry teaching involves the explanation of most phenomena in terms of atomic and molecular models. The main challenge for the student is the creation of mental three-dimensional images of molecules. Unfortunately, many students find the visualisation of the spatial arrangements of molecules a difficult task. For this reason, chemistry teaching has seen the introduction of many innovative teaching tools in an attempt to bring the subject to life for students. Until recently, the cost of computer hardware has prohibited the extensive use of computers within the undergraduate chemistry curriculum. However, the desktop computer has provided a cost-effective platform for developing integrated courseware that presents abstract concepts to the chemistry student. This thesis begins with a review of the design and evaluation of computer-based learning, together with the integration of computers into chemistry education. Two studies then describe the design, implementation and evaluation of novel computer-aided learning material that combines computational chemistry tools and multimedia courseware. The first study assesses the feasibility of integrating interactive three-dimensional molecular modelling into tutorial instruction to provide a visualisation tool for undergraduate organic chemistry. A detailed evaluation has provided substantial evidence concerning the effectiveness of this technique. The second study involves the design of instructional courseware that combines interactive computational chemistry tools and 'talking head' video narration. An innovative training tool that allows medicinal chemists to study analytical chemistry techniques is described. The evaluation of a prototype package has revealed valuable information concerning the combination of dynamic and interactive media. Emerging guidelines for the integration of computational chemistry tools and interactive molecular modelling into multimedia courseware and suggestions for further work are proposed.