Darmstadt, Techn. Universiẗat, Diss., 2003. / Dateien im PDF-Format.

Darmstadt, Techn. Universiẗat, Diss., 2000. / Dateiformat: tar.gz, Dateien im PDF-Format.

Darmstadt, Techn. Universiẗat, Diss., 2002. / Dateiformat: tar.gz, Dateien im PDF-Format.

Chemnitz, Techn. Universiẗat, Diss., 2003. / Datei im PDF-Format.

Thesis (MScIng)--University of Stellenbosch, 2005. / Non-Latin script record Bibliography. Also available via the Internet.

Thesis (Ph. D.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas at Austin, 2002. / Vita. Includes bibliographical references. Available also from UMI Company.

Not available / text

Cigarette smoke (CS) exposure is the leading cause of preventable death in the United States contributing to over 480,000 deaths a year with over 300 billion dollars in CS related costs spent per year. While the dangers of CS exposure have been studied and characterized for decades being largely attributed to reactive oxygen species and oxidative stress, increasing evidence suggests that reactive aldehydes in CS, specifically the α,β-unsaturated aldehyde acrolein, are responsible for many of the negative pathologies associated CS exposure. Previous work has shown that acrolein can bind directly to a number of cellular proteins containing redox sensitive cysteine residues. The non-receptor tyrosine kinase Src contains nine cysteine residues and is known to be activated in response to CS and oxidative stress. Despite being the first characterized and one of the most widely studied oncogenes, the exact mechanism for Src activation remains unclear. In the current studies we examined the effects of acrolein on Src activation and the resulting outcomes on the lung epithelium in an effort to better understand how reactive electrophiles in CS contribute to the development of lung disease. To determine the effects of acrolein on Src activation, we first exposed NCI-H292 cells to acrolein and measured activity by western blot. We observed an increase in Src activity detected by an increase in Src phosphorylation at Y416 and an increase in phosphorylation of Src target proteins Caveolin1 and p120. Interestingly the increase in activation occurred without dephosphorylation of the inhibitory phosphorylated tyrosine Y527. Using biochemical-labeling strategies we identified Src as a direct target of acrolein adduction in vitro and in vivo, and we used mass spectrometry to confirm acrolein adduction to cysteine residues C245, C277 and C487, all which have been implicated in a redox dependent Src activation mechanism. Furthermore, increased Src activity following acrolein exposure was confirmed using an in vitro kinase activity assay and recombinant Src in a cell free system. To study the effects of acute acrolein exposure on lung epithelial function we exposed cultured mouse tracheal epithelial cells (MTECs) to acrolein and show impaired epithelial barrier function, measured by a decrease in trans epithelial resistance (TER) and increased epithelial permeability to FITC-dextran, which could be prevented using the Src inhibitor PP2. Src inhibition also attenuated acrolein-induced loss of E-cadherin and ZO-1. Acute exposure of C57BL/6 mice to acrolein (5 ppm for 4 hrs) led to increased epithelial permeability, measured by enhanced leakage of i.v. injected FITC-dextran into the airspaces, and induction of HO-1 in the lung while chronic acrolein exposure resulted features of epithelial to mesenchymal transition including a reduction of E-cadherin, increased vimentin, increased expression of MMP9 and increased collagen deposition. Chronic acrolein exposure in vitro resulted in a reduction of E-cadherin that could be prevented using the Src inhibitor AZD0530. Together our studies demonstrate that Src is a direct target for acrolein and plays an important role in epithelial alterations due to acrolein exposure. This work provides further insight into a potential mechanism involved in the development of cigarette smoke related disease and could provide a potential target for novel therapeutics.

Bismuth molybdates have long been known as active catalysts for selective oxidation of olefins. There are several phases of bismuth molybdates but only three of them are known to be active for partial oxidation of propylene to acrolein, namely, α, β, and γ bismuth molybdates. A significant amount of work has been carried out and reported in the literature, aiming to understand the reaction mechanisms so as to control the reaction process. It has been revealed that the oxidation reaction follows the redox mechanisms and lattice oxygen plays a key role as the main oxygen source for the reaction and controls the catalyst performance. The properties of the lattice oxygen are influenced by the bulk crystalline structure of the catalyst. Therefore, it is possible that the crystal structure influences the performance of the catalyst in promoting the partial oxidation reaction. However, there appears to be a lack of detailed reports in the literature on the relationship between the bulk crystal structure and the activity and selectivity of the catalyst for the partial oxidation reaction. The work reported in this thesis has been designed to achieve an improved understanding of the catalyst structure in relation to the activity and selectivity of the catalyst for the partial oxidation of propylene to acrolein. / In order to fulfil the objectives of this study, several investigation steps have been taken, namely 1) acquiring and analysing the catalyst structural parameters under real reaction conditions as well as at room temperature by means of neutron diffraction and X-ray diffraction, 2) obtaining kinetics from experimentation using a packed-bed reactor operating under differential reactor mode so as to eliminate the mass diffusion effect, and 3) developing and proposing reaction mechanisms which contain events that occur on the crystalline structure of the catalysts, particularly lattice oxygen, during the reaction. Characterisation of the structure of the catalysts has been carried out by means of In-situ neutron diffraction, which has the ability to probe the crystal structure at atomic level. The structure is characterised under simulated reaction conditions to investigate the dynamics of the crystal structure, particularly lattice oxygen, during the reaction. The In-situ diffraction studies have uncovered the relationship between the crystal structure of bismuth molybdates and their selectivity and activity towards the catalytic partial oxidation of propylene to acrolein. The possible active lattice oxygen in the bismuth molybdate structures has been identified. The active lattice oxygen ions are responsible for maintaining redox balance in the crystal lattice and thus control the catalyst activity and selectivity. Mobile oxygen ions in the three bismuth molybdate crystal phases are different. The mobile oxygen ions are O(1), O(11), and O(12) in the α phase; O(3), O(11), O(16), and O(18) in the β phase; and O(1) and O(5) in the γ phase. / The mobile lattice oxygen ions are proposed to be the source of the oxidising oxygen responsible for the selective oxidation of propylene to acrolein. One common feature of all mobile oxygen ions, from a catalyst crystal structure point of view, is that they are all related to molybdenum ions rather than bismuth ions in the lattice. By modifying the physical and chemical environment of the molybdenum oxide polyhedra, it is possible to modify the catalyst selectivity and activity. The diffraction diagnoses have also shown that molybdenum oxide polyhedra in all bismuth molybdate are unsaturated. In contrast, the bismuth oxide polyhedra are over charged. The co-existence of molybdenum ions that are co-ordinately unsaturated with bismuth ions that are over valence-charged promote the formation of allyl radical such as those found in the partial oxidation of propylene to acrolein. The molybdenum ions become propylene-adsorbing sites while the bismuth ions are the active sites to attract hydrogen from the adsorbed propylene, leading to the formation of the allyl intermediate. Oxygen ions from the mobile lattice oxygen are a more moderate oxidant than molecular oxygen. With their mild activity, the partially oxidised products are the main products such as acrolein and formaldehyde when oxygen ions react with the allyl intermediate while more complete combustion products such as carbon oxides and organic acids become the side products. / Investigation into the kinetics and reaction mechanisms has revealed the aforementioned evidence to support the role of the mobile lattice oxygen ions in the partial oxidation of propylene to acrolein. The kinetic experiments have employed the power rate law to model the kinetic data. The model shows that the reaction orders in propylene and oxygen concentrations are a function of the reaction temperature. The reaction order in propylene increases with reaction temperature, from 0.6 at 300°C to 1.0 at 450°C for all the bismuth molybdate catalysts, while the reaction order in oxygen decreases from 0.6 at 300°C to 0 at 450°C. The activation energies are 99.7, 173, and 97.7 kJ.mol-1 for α-Bi2Mo3O12, β-Bi2Mo2O9, and γ-Bi2MoO6, respectively. The changes in reaction orders with respect to propylene and oxygen indicate that the reaction occurs through the redox mechanisms, using the mobile lattice oxygen. The structural dynamics identified earlier explains the decrease in the acrolein selectivity at high temperatures (ca above 390°C). At these temperatures, the mobile oxygen becomes more mobile and more active. As a result, as the mobility of the oxygen ions increase, their reactivity also increases. The increase in the oxygen reactivity leads to unselective, complete oxidation reaction, forming the complete oxidation products CO2 and H2O. The reduction-reoxidation of bismuth molybdate is controlled by the diffusion of oxygen ions in the lattice, because the reduction sites do not have to be adjacent to the oxidation sites. The oxygen diffusion rate is in turn controlled by how mobile the lattice oxygen ions are. / Hence, the mobile oxygen ions discussed earlier control the catalyst activity in catalysing the reaction of propylene partial oxidation. The examination of several reaction mechanism models has given further evidence that the propylene partial oxidation to acrolein occurs via the redox mechanism. In this mechanism, the rate of acrolein formation depends on the degree of fully oxidised sites in the bismuth molybdate. The oxidised sites affect the apparent reaction orders in propylene and oxygen and thus control the kinetics of partial oxidation of propylene to acrolein. The more easily the reduced catalysts are reoxidised, the more active the catalysts in converting propylene to acrolein. A set of reaction steps has been proposed, which adequately reassembles the reaction mechanism. Side product reactions are also identified and included in the mechanisms. The present thesis has revealed a much detailed insight into the role of lattice oxygen in the catalytic partial oxidation of propylene to acrolein over bismuth molybdates and established the relationship between structure and activity and selectivity of the catalyst. This work has laid a foundation for future catalyst design to be based on structural knowledge of the catalysts.