M.Sc. / An annual production of approximately 46 million metric tons of polyolefins worldwide, emphasizes the industrial importance of this product and the polymerisation process. Olefins are the basic building block of the petrochemical industry and are therefore readily available and cheap. Reactivity of olefins decreases from ethylene to propylene to 1-octene and makes the study of polymerisation catalysts more complex, seeing that the activity of a catalyst differs from monomer to monomer. In this study zirconocene complexes with bridged cyclopentadienyl ligands have been prepared and investigated as , possible catalysts for the polymerisation of higher aolefins. Fulvenes have been reductively coupled and used as ligands for zirconium complexes. Steric bulk of the substituents on the ligand have been increased and changes in the polymeric products have been studied. The tacticty, endgroups and chain lengths of the polyolefins have been investigated. There is currently a considerable interest in the development of 'non-metallocene' catalysts as alternatives for the polymerisation and oligomerisation of a-olefins. Chelating diamide complexes of Group 4 metals have been the focus of much attention and these compounds have shown moderate to high reactivity. However, only a few examples of the corresponding chelating alkoxides are known. In this study, alkoxide complexes of zirconium and titanium have been prepared with Schiff bases as ligands. These complexes have been evaluated as polymerisation catalysts and the products have been studied. The titanium complexes were more active than the zirconium analogues. The narrow molecular weight distribution of the polyolefins gave evidence that these catalysts are single-sited catalysts.

No description available.

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

Nucleic acids store genetic information in the sequence of nucleobases. Through duplex formation and template directed synthesis, the information stored in nucleic acids determines their three-dimensional structure and function. Nucleic acids are essential molecules for biological processes and have been used in nanotechnology. Modified nucleic acids have been synthesised that still form duplexes and can be tolerated by enzymes, suggesting that it is possible to construct a synthetic system comparable to nucleic acids, orthogonal to nucleic acids. This thesis describes the synthesis of a new class of synthetic information molecule, characterisation of the duplex forming properties, and attempts at templated oligomerisation reactions. The new synthetic information molecule is based on the phenylacetylene oligomer framework developed by Moore and co-workers. Recognition was achieved via a base-pair that is made from a single point high affinity H-bond, with phenol as the H-bond donor (D) and phosphine oxide as the H-bond acceptor (A). The Sonogashira coupling was used to construct the phenylacetylene oligomer backbone. The AA, DD and AD 2-mers were synthesised and complementary 2-mers showed cooperative duplex formation. No intramolecular H-bonding due to folding was observed in the AD mixed 2-mer. Longer oligomers were synthesised using a method of oligomerisation and chromatographic separation by reverse-phase preparatory HPLC. Homo-oligomers up to the 7-mer were isolated and binding studies between complementary all donor, all acceptor homo-oligomers showed increasing duplex stability with each additional recognition unit in the oligomer chain. Oligomers containing both acceptor and donor recognition modules in the same chain were synthesised and NMR dilution studies were used to investigate their ability to fold. Preliminary experiments were carried out to evaluate the ability of these information molecules to template oligomerisation reactions, but when reactions were carried out at concentrations low enough for a significant template effect, no coupling reactions were observed.

Wei Chunmei. / "September 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 137-140). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Protein deposition in the form of amyloid fibrils is the hallmark of more than 40 human pathologies, including Alzheimer's disease (AD) and Parkinson's disease (PD). Misfolded protein oligomers formed as intermediates during the aggregation process have been strongly implicated in the onset and progression of these diseases. In this thesis, I describe our efforts to uncover molecular agents that can reduce the toxicity caused by protein aggregation via targeting the generation, the physiochemical properties or the membrane affinity of oligomeric species. We employed an integrative approach combining in vitro techniques, including chemical kinetics, atomic force microscopy, and biophysical measurements, and in vivo methods, including neuroblastoma cells and C. elegans models of AD and PD, to identify a range of small molecules and antibodies that can suppress the toxicity related to protein aggregation through a variety of mechanisms. In Chapter 3, we show that the deleterious effects of protein aggregation can be suppressed in AD and PD worms by interfering with the aggregation rates of the amyloid-β peptide (Aβ) and the α-synuclein protein (αS). In Chapter 4, we resolve the mechanism of action for a molecule that enhances the rate of Aβ42 aggregation in AD worms with the result that toxicity is reduced, and find that it potentiates the secondary nucleation microscopic step in vitro. In Chapter 5, we characterize molecules and antibodies that modify the physiochemical properties and self-association of oligomers comprised of several proteins into clusters with reduced diffusibility. In Chapter 6, we classify a family of molecules that protect the cell by displacing several types of oligomeric species from the membrane through a generic mechanism. These results demonstrate strategies by which one can target the aggregation process to alter its resulting toxicity, provide insight into modifying the properties of the most deleterious species associated with protein aggregation and suggest that the protection of the cell from the oligomer-induced cytotoxicity associated with numerous protein misfolding diseases is a promising strategy to combat protein misfolding diseases.

M2 muscarinic receptor extracted from Sf9 cells in cholate-NaCl differs from that extracted from porcine sarcolemmal membranes. Whereas the latter has been shown to exhibit non-competitive effects in the binding of N-methylscopolamine (NMS) and quinuclidinylbenzilate (QNB), which can be explained in terms of cooperativity within a receptor that is at least tetravalent, binding to the former is essentially competitive. Levels of cholesterol in Sf9 membranes were only 5% of those in sarcolemmal membranes and were increased to about 100% by means of cholesterol-methyl-β-cyclodextrin. M2 receptors extracted from CHL-treated Sf9 membranes resembled those from heart; that is, cholesterol induced a pronounced heterogeneity detected in the binding of both radioligands, including a shortfall in the apparent capacity for [3H]NMS, and there were marked discrepancies in the apparent affinity of NMS as estimated directly and via the inhibition of [3H]QNB. The data can be described quantitatively in terms of cooperative effects among six or more interacting sites, apparently within an oligomer. Cholesterol also was found to increase the affinity of the receptor for NMS and QNB, and the effect was examined for its possible relationship to the known interconversion of cardiac muscarinic receptors between an agonist-specific (R*) and an antagonist-specific (R) state. Cholesterol and N-ethylmaleimide (NEM) were compared for their effect on the affinity of NMS, QNB and four muscarinic agonists, and the data were assessed in terms of an explicit mechanistic model for a receptor that interconverts spontaneously between two states. The data can be described equally well by an effect of cholesterol on either the distribution of receptors between R and R* or the affinity of all ligands for both states, with an accompanying effect of NEM on either the affinity or the distribution between states, respectively. Since NEM is known from other data to favor R* over R, cholesterol appears to increase affinity per se. Cholesterol therefore is a determinant of affinity and cooperativity in the binding of orthosteric ligands to the M2 receptor. Both effects are observed in solution and therefore appear to arise from a direct interaction between the lipid and the receptor.

Hop cell wall material (CWM) extracted from hop leaves (hamulus lupulus) was purified and characterized. The total sugar content, uronic acid content and monosaccharide composition of the CWM were determined. Galacturonic acid is the major component in the CWM. A mixture of unsaturated oligogalacturonides were released from purified hop CWM by autoclaving. The biological activity of these oligomers was tested for their ability to elicit phytoalexins. The oligomer with hexagalacturonic acid possessed the greatest biological activity. Column chromatography and high-pH anion exchange chromatography were used for the sample separation and purification. Fast-atom-bombardment mass spectrometry (FAB-MS) was used for the structure elucidation. The FAB-MS spectrum showed that the unsaturated galacturonosyl residue was located at the nonreducing terminus of the oligomer. / Graduation date: 1993

M2 muscarinic receptor extracted from Sf9 cells in cholate-NaCl differs from that extracted from porcine sarcolemmal membranes. Whereas the latter has been shown to exhibit non-competitive effects in the binding of N-methylscopolamine (NMS) and quinuclidinylbenzilate (QNB), which can be explained in terms of cooperativity within a receptor that is at least tetravalent, binding to the former is essentially competitive. Levels of cholesterol in Sf9 membranes were only 5% of those in sarcolemmal membranes and were increased to about 100% by means of cholesterol-methyl-β-cyclodextrin. M2 receptors extracted from CHL-treated Sf9 membranes resembled those from heart; that is, cholesterol induced a pronounced heterogeneity detected in the binding of both radioligands, including a shortfall in the apparent capacity for [3H]NMS, and there were marked discrepancies in the apparent affinity of NMS as estimated directly and via the inhibition of [3H]QNB. The data can be described quantitatively in terms of cooperative effects among six or more interacting sites, apparently within an oligomer. Cholesterol also was found to increase the affinity of the receptor for NMS and QNB, and the effect was examined for its possible relationship to the known interconversion of cardiac muscarinic receptors between an agonist-specific (R*) and an antagonist-specific (R) state. Cholesterol and N-ethylmaleimide (NEM) were compared for their effect on the affinity of NMS, QNB and four muscarinic agonists, and the data were assessed in terms of an explicit mechanistic model for a receptor that interconverts spontaneously between two states. The data can be described equally well by an effect of cholesterol on either the distribution of receptors between R and R* or the affinity of all ligands for both states, with an accompanying effect of NEM on either the affinity or the distribution between states, respectively. Since NEM is known from other data to favor R* over R, cholesterol appears to increase affinity per se. Cholesterol therefore is a determinant of affinity and cooperativity in the binding of orthosteric ligands to the M2 receptor. Both effects are observed in solution and therefore appear to arise from a direct interaction between the lipid and the receptor.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 472-488). Also available on the Internet.