This dissertation investigates the nature of submarine landslides along the deformation front of the northern Cascadia subduction zone. As the first slope stability analysis on the west coast of Vancouver Island, this study covers a variety of large-scale tectonic to small-scale, site-specific factors to investigate the nature of slope failure. Slope failure occurred mainly on the steep slopes of frontal ridges that were formed by compressive forces due to the subduction of the Juan de Fuca plate. Multi-beam swath bathymetry data are used to study the morphology of the whole margin and the geometry of two Holocene landslides that serve as representative examples. The overall margin stability is estimated using the critical taper theory, and a first-order limit equilibrium slope stability analysis provides threshold values for external forces to cause slope failure. The present-day pore pressure regime at different sites of the Cascadia margin is estimated from log-density data and expected ground accelerations are calculated via ground motion attenuation relationships. A comparison to threshold values derived from the limit equilibrium analysis suggests that, at present, slope stability is more sensitive to overpressure than to earthquake shaking. Differences in power spectral density derived from OBS-velocity data imply a slightly amplified ground response at the ridge crest compared to sites along the continental shelf and abyssal plain. Apart from estimating the trigger mechanisms of submarine landslides offshore Vancouver Island, a particular consideration is given to the potential link between slope failure and methane hydrate occurrence. The history of the gas hydrate stability zone (GHSZ) boundaries is investigated using information on regional sea-level history. Assuming colder ocean-bottom temperatures during the Holocene, a gradual shoaling of the BSR is inferred, which potentially could have caused hydrate melting. Pore pressure due to hydrate dissociation, as estimated by a previously developed method, varies over several orders of magnitude. Depending on sediment permeability, overpressure ratios can be comparable to threshold values. The two Holocene landslides are modeled numerically using a two-dimensional finite difference code in order to recreate the along-strike variability in ridge geometry and slide morphology observed along the northern Cascadia margin. Geometry and morphology correlate with the two prevalent slide mechanisms and model results suggest that sediment yield strength and average slide thickness are associated with the slide mechanism as well. / Graduate / 0373 / nscholz@uvic.ca

L’analyse et le contrôle de la qualité pharmaceutique suivent des recommandations internationales en évolution constante. Les exigences de pureté et de stabilité des substances actives sont fondamentales pour assurer l’efficacité et la sécurité des médicaments. A ce jour, les approches analytiques développées discriminent les niveaux de qualité physique et chimique des matériaux d’usage pharmaceutique. Une démarche analytique exhaustive permettant d’une part, l’évaluation de la pureté et de la stabilité physico-chimique des substances actives pharmaceutiques, et d’autre part, la corrélation entre les transformations physiques et chimiques, reste à établir. Ce travail est fondé sur l’exploitation des informations de type thermodynamique, cinétique et structural relatives aux transformations susceptibles d’affecter les substances à l’état solide et en solution. La stratégie développée comporte deux axes. Le premier est un axe exploratoire visant à caractériser la réactivité chimique et l’existence de phases solides alternatives constituées par les polymorphes et des hydrates. Le second axe consiste en la combinaison des méthodes d’analyse thermodynamique, spectrale et chimique, pour l’établissement du profil de stabilité de la substance active. Deux substances actives d’origine chimique entrant dans la composition de médicaments orphelins administrés à l’état solide permettent la mise en application de ce travail. / The international recommendations for the quality control of drugs are in continuous improvement. The purity and stability of drug substances is crucial to ensure the efficacy and safety of medicines. Traditional analytical approaches are either physical or chemical oriented. An integrated approach allowing (i) the assessment of purity and stability of drug substances and (ii) the correlation of physical and chemical phenomena are lacking. This work is based on the processing of thermodynamic, kinetic and structural information related to the transformations occurring in solution and in the solid state. The chosen strategy begins with the characterization of chemical reactivity of the drug substance, as well as the research of possible phase transitions to polymorphs and hydrates. A combination of thermodynamic, spectral and chemical analyses is then employed to establish an exhaustive stability profile. Two orphan drugs used in the solid state are examined as cases studies.

Ice recrystallization during cryopreservation results in cell death and decreased cell viabilities due to cellular damage. This is a significant problem particularly in regenerative medicine where decreased cell viabilities post-thaw affect the success of the therapy. Given the success of these therapies to treat various diseases, the development of novel cryprotectants which have the ability to inhibit ice recrystallization during freezing and thawing are urgently required. Current cryoprotectant such as dimethyl sulfoxide, is associated with cytotoxicity in the clinical settings and thus are not optimal cryoprotectants. Our laboratory is interested in the rational synthesis of non-cytotoxic small molecules which possess the property of ice recrystallization inhibition (IRI) activity. Previously, the Ben laboratory has demonstrated that simple monosaccharides possess moderate ice recrystallization inhibition activity and that this activity is linked to hydration. The “compatibility” of the carbohydrate within the three-dimensional hydrogen bonded network of water is inversely proportional to its IRI activity. Hydration has previously been directly linked to the stereochemical relationship of individual hydroxyl groups on the carbohydrate. Additionally, it has been proposed that intramolecular hydrogen bond formation and hydrogen bonding cooperativity has a large effect on the water structure thus impacting hydration. Structure-function work has suggested that the presence of an amine as a hydrogen donor at the endocyclic position within the pyranose ring maybe beneficial to IRI activity. Thus, the first part of this thesis describes the synthesis and IRI activity of D-glucose and D-galactose based azasugars and its analogues. These azasugars have replaced the endocyclic ring oxygen with an amine. These azasugars and their analogues were found to possess moderate to potent IRI activity suggesting that hydrogen bond donation may be important for hydration and thus, IRI activity at the endocyclic ring oxygen. During the development of these azasugars, the Ben laboratory developed carbohydrate-based surfactants and hydrogelators possessing unprecedented IRI activity. A potential use of molecules possessing IRI activity is towards the inhibition of gas hydrate formation. Gas hydrates are ice-like solids containing gases within a highly ordered network of water molecules. These gas hydrates tend to accumulate in oil and gas pipelines posing significant dangers as the build-up of solid material leads to blockages in the pipeline reducing flow. Previous work had demonstrated the use of antifreeze proteins possessing potent IRI activity in inhibiting gas hydrate formation. However, their complex structure limits commercial use. Thus, the second part of the thesis describes the use of the azasugars, carbohydrate-based surfactants and hydrogelators in inhibiting gas hydrate formation. The effectiveness of the small molecules is compared to a commercial inhibitor PVP 10. Some of these small molecules were significantly better inhibitors of gas hydrate formation than the currently utilized inhibitor PVP 10. The low molecular weights of these small molecules, easy synthesis and potency make them excellent alternatives to PVP 10. However it was found that while some of the structural features in the small molecules may be amenable to both activities, it seems that the ability to inhibit ice recrystallization is not a good indicator of a compounds ability to inhibit gas hydrate formation. In a continuing effort to develop novel small molecule IRIs, the Ben laboratory has develop three classes of compounds. These include: carbohydrate-based surfactants and hydrogelators, lysine-based surfactants and truncated C-linked glycopeptides. Structure-function work utilizing these compounds revealed that presence of long alkyl chains, an amide linkage and the presence of an open-alditol chain are all important to IRI activity. However, the surfactant-like nature limits their use in cryopreservation and thus prompted the discovery of phenoxyglycosides as IRI active molecules. The structural features of these recently developed small molecules were combined to generate novel small molecule IRIs which do not resemble surfactants. These novel small molecules included “disaccharides” which possessed an aryl group at the anomeric position of a pyranose ring and an open-alditol chain linked via an amide bond. Additionally, N-cycloalkyl-D-aldonamides and N-phenyl-D-aldonamides were also synthesized. Of these novel small molecules, two very potent IRI active molecules were discovered: a “disaccharide” possessing an aryl group at the anomeric position with the open-alditol chain of D-galactose linked via an amide bond at C3 and N-phenyl-D-arbonamide. Both of these small molecules were assessed for their ability to cryopreserve hematopoietic stem cells. Unfortunately, the additional of these compounds failed to improved percent cell viabilities as compared to DMSO.

With a view to obtaining information on the nature and extent of molecular motion of enclathrated "guests" and their interaction with the "host" lattices, nuclear magnetic resonance absorption of ten guest species included in the clathration voids of fully deuterated hydrates has been studied from a temperature of 77ºK upwards. The F¹⁹ resonance line shapes for CF₄ and SF₆ and the H¹ resonance line shape for ethylene oxide (C₂H₄0) in their respective clathrate hydrates indicate that these molecules are but little restricted by the walls of the clathrate cavities, and reorient freely about chosen axes of symmetry at low temperatures and at random at higher temperatures. Above 150ºK, a limited isotropic translation, or "rattling", of an SF₆ guest molecule up to a distance of [formula omitted] from the centre of the clathration volume has been demonstrated. Proton resonance has been studied for propane in two specimens of the clathrate hydrate, one of which was richer in guest content than the other. For these two specimens it has been suggested that, below 160ºK, propane assumes a staggered C₂ configuration inside the clathrate cavity. Molecular C₂ - axis reorientations superposed on methyl reorientations have been proposed, and a thermal activation energy barrier of 1.70 ± 0.08 kcal/ mole has been calculated for the above motion from spin-lattice relaxation time measurements in the 77ºK - 110°K range. Closer to the melting point of the two specimens, diffusion of propane through the host lattice has been indicated, and diffusional activation energies of 1.40 ± 0.02 kcal/mole and 0.75 ± 0.05 kcal/mole have been obtained for the guest - rich and guest - poor specimens, respectively. In sharp contrast to the above results, the low temperature proton resonance of three halomethanes, CH₃X(X = CI, Br, I), inside hydrate host cavities has revealed definite constraints to reorientational and translational motion, the second moment data indicating only low-amplitude oscillatory motions of the CH₃ groups in these clathrates. A triplet line shape has been observed for the CH₃Br clathrate at 77°K. At higher temperatures, expansion of the hydrate lattices has been proposed, which permits free C₃- reorientations of the CH₃ groups of the three guest molecules. From the associated linewidth transitions, activation energies of 2.48 ± 0.32, 9.30 ± 0.25, and 6.80 ± 0.50 kcal/mole have been calculated for the potential barrier hindering methyl reorientation in the CH₃Cl-, CH₃Br-, and [formula omitted] hydrates, respectively. The motional model proposed for this temperature range is adequately supported by measurements of H¹ spin - lattice relaxation times. For the dichloromethane clathrate hydrate, a clearly resolved doublet characteristic of rigid proton pairs has been obtained at 77°K. The possible existence at low temperatures of an aligned guest molecule in a suitably-sized cavity is thereby indicated. A line shape analysis of this doublet, performed on an IBM 7040 computer, yielded an accurate H-H interatomic distance of 1.73Å for the 'guest' dichloromethane molecule. This value has been discussed in the light of results from earlier microwave studies of dichloromethane. The proton resonance linewidth and second moment results between 77°K and 286°K for i-amyl groups included as guests in the clathrate hydrate of (i-C₅H₁₁)₄NF have been interpreted in terms of simple motional models of these guest moieties. The results complement the reported crystal structure of this clathrate. For the analogous hydrate containing 'guest' n-butyl groups, proton second moments in the same temperature range have supported the disordered guest structure reported from a previous x-ray diffraction study. In addition, hysteresis has been demonstrated in the second moment curve of this clathrate beyond 248°K, and this has been ascribed to a phase transition. / Science, Faculty of / Chemistry, Department of / Graduate

An N.M.R. study of the clathrate hydrates of SF₆, C₃H₆ and (CH₃)₂CO has been carried out to examine the type of motion a guest molecule undergoes in the clathrated cavity. ¹⁹F nuclear magnetic resonance spectra of Sulphur Hexafluoride Hydrate and Deuterate show isotropic rotation or reorientation about an axis at random of the SF₆molecule. ¹H magnetic resonance spectra of Cyclopropane Deuterate show highly restricted rotation up to 240°K, and then free rotation about C₃-axis at high temperatures. ¹H magnetic resonance spectra of Acetone Deuterate show that the CH₃-group is rotating even at 77°K, and self diffusion occurs at 172°K. The barrier hindering diffusion of the (CH₃)₂CO has been calculated and is 3.9 kcal/mole. / Science, Faculty of / Chemistry, Department of / Graduate

[pt] Hidratos de gás natural são sólidos cristalinos, formados pela associação de moléculas de água a certos hidrocarbonetos leves, sob condições adequadas de pressão e temperatura. No cenário de produção de petróleo offshore, sua ocorrência é motivo de preocupação constante para a indústria de petróleo, pois podem resultar em bloqueios das linhas submarinas e interrupção completa do fluxo. Os custos de prevenção, no entanto, têm se tornado proibitivos, forçando uma mudança conceitual em projetos e privilegiando métodos de gerenciamento desse risco. Dentro dessa estratégia, uma vertente promissora é a avaliação das propriedades reológicas de suspensões de hidrato: seu conhecimento pleno pode determinar as condições em que a formação de hidratos no sistema submarino não vai resultar em bloqueio, constituindo-se em ferramenta valiosa na análise de risco de diversas atividades. O presente trabalho se insere nesse esforço, empregando uma emulsão combinada a ciclopentano (agente formador de hidratos à pressão atmosférica) e examinando diferentes metodologias. Para cumprir esse objetivo, estudou-se o comportamento reológico de emulsões água em óleo, com e sem ciclopentano, sob condições de formação de hidratos, submetidas a ensaios rotacionais e oscilatórios. A resposta do sistema a variações em parâmetros térmicos (temperatura mínima e taxa de resfriamento) e hidrodinâmicos (cisalhamento) também foi brevemente investigada. / [en] Hydrates of natural gases are crystalline solids, composed of water and light hydrocarbon molecules that assemble in special structures under certain conditions of pressure and temperature. For most offshore production facilities, it is a major concern for the oil and gas industry, given that it can lead to a full blockage of subsea and a complete stop of petroleum flow. However, avoidance costs have grown too high, so the industry began shifting towards a risk management methodology. Within this strategy, a promising field is the evaluation of rheological properties of hydrate slurries: its full understanding can help predicting if hydrates formation will lead to a blockage, becoming a valuable tool in risk assessment of many activities. The present work is a part of this effort, employing an emulsion combined with cyclopentane (known hydrate former at atmospheric pressure) to evaluate different methods. In order to fulfill this objective, the rheological behavior of water-in-oil emulsion, with and without cyclopentane, was studied in rotational and oscillatory tests, under hydrate forming conditions. The system response to changes in thermal (minimum temperature and cooling rate) and hydrodynamic (shear) parameters was also briefly investigated.

Yes / This investigation reports the first study to predict natural gas hydrate formation using both Aspen HYSYS® and HydraFlash software for various gas compositions and thermodynamic inhibitors (monoethylene glycol [MEG] concentrations at 10, 20, 30, and 40 wt.% and methanol concentrations at 10 and 20 wt.%). The simulated predictions are compared with the results of the experimental data in the literature. It has been shown that HydraFlash software can accurately predict hydrate formation conditions for a given industrial case, without having to carry out costly experimental work. This work also evaluated the effect of inhibitors and it appears that inhibitor type and concentration are determined according to condition of gas composition. MEG is consequently selected as the most ideal hydrate inhibitor for the industrial case. This also was confirmed through COSMO-RS studies in which the sigma profile and sigma potential of the considered inhibitors were obtained and presented using density functional (DFT) calculations to verify the hydrogen bonding affinities of the inhibitors to water molecules. HydraFlash was utilized to predict the dissociation conditions of hydrates under the influence of a high concentration of MEG inhibition, reaching up to 40 wt.% at 313 K and a pressure of 311.1 bar. Finally, it is shown that both software packages are quite accurate and useful tools for the prediction of hydrate for simple systems. However, HydraFlash can simulate more complex systems, including different types of salts at higher pressures. Investigation results indicate insightful guidance for accurately predicting hydrate dissociation under simulated conditions. / The authors would also like to thank the Turkish National Agency for offering an Erasmus student grant for Mr. Nejmi Söyler under the Erasmus+ Program Action 1 throughout the training period.

Methane hydrates are frozen deposits of methane and water found in high pressure or low temperature sediments. When these deposits destabilize, large quantities of methane can be emitted into the atmosphere. This is significant to climate change because methane has 25 times more greenhouse gas potential than Carbon Dioxide. Worldwide, it is estimated there are between 2500 and 10000 gigatons of methane stored in hydrate deposits. This represents more carbon than all fossil fuels on Earth. It is estimated that between 200 and 2000 gigatons of methane are stored in hydrates in Arctic waters acutely vulnerable to greenhouse warming. Over the last decade, researchers have identified instances of hydrate destabilization that have already begun. To gain insight into the potential climatic effects widespread hydrate dissociation would have, researchers have examined hydrate dissociation during the Paleocene Eocene Thermal Maximum 55 million years ago as a geologic precedent. In this period, large-scale hydrate dissociation contributed to 5-8 degree Celsius warming worldwide. If such a climatic shift were to transpire today, impacts on society would be enormous. There is currently a debate in the scientific community as to whether the risk of methane hydrate dissociation is relevant to the present generation. One side argues that not enough methane could be emitted into the atmosphere from today’s hydrate sources to have a meaningful impact on climate warming, where the other side contends that more than enough methane could be emitted from present day hydrate deposits to cause significant impacts to the global greenhouse effect. Given the information currently known about hydrates, it is reasonable to conclude there is a moderate risk of widespread destabilization that could impact global climate change in the coming decades. Significant acceleration of the conversion to alternative energies and implementation of geoengineering strategies should be considered.

La cristallisation des hydrates pendant la production de pétrole est une source de risques, surtout liés au bouchage des lignes de production dû à l’agglomération des hydrates. Pendant l'extraction de pétrole, l'huile et l'eau circulent dans le pipeline et forment une émulsion instable. La phase eau se combine avec les composants d'hydrocarbures légers et peut former des hydrates. La cristallisation des hydrates a été intensivement étudiée, principalement à faible fraction d’eau. Cependant, lorsque le champ de pétrole devient mature, la fraction d’eau augmente et peut devenir la phase dominante, un système peu étudié concernant à la formation d'hydrates. Plusieurs techniques peuvent être combinées pour éviter ou remédier la formation d'hydrates. Récemment, une nouvelle classe d'additifs a commencé à être étudiée : Inhibiteurs d'Hydrates à Bas Dosage (LDHI), divisés en Inhibiteurs Cinétiques (KHI-LDHI) et anti-agglomérants (AA-LDHI).Ce travail est une étude paramétrique de la formation d'hydrates à partir de l'émulsion, en variant la fraction d’eau, le débit, en absence et en présence d’AA-LDHI. Les expériences ont été réalisées sur la boucle d'écoulement Archimède, qui est en mesure de reproduire les conditions de la mer profonde. L'objectif de cette étude est d'améliorer la compréhension de la formation d'hydrate et de comprendre comment l'additif dispersant évite l'agglomération. Pour ce faire, un modèle comportemental de la cristallisation pour les systèmes sans et avec additif a été développé. Il a également été proposé une technique pour déterminer la phase continue du système et un mécanisme d'action pour l'anti-agglomérant a été suggéré. / Crystallization of hydrates during oil production is a major source of hazards, mainly related to flow lines plugging after hydrate agglomeration. During the petroleum extraction, oil and water circulate in the flow line, forming an unstable emulsion. The water phase in combination with light hydrocarbon components can form hydrates. The crystallization of hydrates has been extensively studied, mainly at low water content systems. However, as the oil field matures, the water fraction increases and can become the dominant phase, a system less known in what concerns hydrate formation. Actually, several techniques can be combined to avoid or remediate hydrate formation. Recently, a new class of additives called Low Dosage Hydrate Inhibitor (LDHI) started to be studied, they are classified as Kinetic Hydrate Inhibitors (KHI-LDHI) and Anti-Agglomerants (AA-LDHI).This work is a parametric study about hydrate formation from emulsion systems ranging from low to high water content, where different flow rates and the anti-agglomerant presence were investigated. The experiments were performed at the Archimède flow loop, which is able to reproduce deep sea conditions. The goal of this study is enhancing the knowledge in hydrate formation and comprehending how the dispersant additive acts to avoid agglomeration. For this matter, it was developed a crystallization topological model for the systems without and with additive. A technique to determine the system continuous phase and a mechanism of the anti-agglomerant action from the chord length measurements were also proposed.

La cristallisation des hydrates pendant la production de pétrole est une source de risques, surtout liés au bouchage des lignes de production dû à l’agglomération des hydrates. Pendant l'extraction de pétrole, l'huile et l'eau circulent dans le pipeline et forment une émulsion instable. La phase eau se combine avec les composants d'hydrocarbures légers et peut former des hydrates. La cristallisation des hydrates a été intensivement étudiée, principalement à faible fraction d’eau. Cependant, lorsque le champ de pétrole devient mature, la fraction d’eau augmente et peut devenir la phase dominante, un système peu étudié concernant à la formation d'hydrates. Plusieurs techniques peuvent être combinées pour éviter ou remédier la formation d'hydrates. Récemment, une nouvelle classe d'additifs a commencé à être étudiée : Inhibiteurs d'Hydrates à Bas Dosage (LDHI), divisés en Inhibiteurs Cinétiques (KHI-LDHI) et anti-agglomérants (AA-LDHI).Ce travail est une étude paramétrique de la formation d'hydrates à partir de l'émulsion, en variant la fraction d’eau, le débit, en absence et en présence d’AA-LDHI. Les expériences ont été réalisées sur la boucle d'écoulement Archimède, qui est en mesure de reproduire les conditions de la mer profonde. L'objectif de cette étude est d'améliorer la compréhension de la formation d'hydrate et de comprendre comment l'additif dispersant évite l'agglomération. Pour ce faire, un modèle comportemental de la cristallisation pour les systèmes sans et avec additif a été développé. Il a également été proposé une technique pour déterminer la phase continue du système et un mécanisme d'action pour l'anti-agglomérant a été suggéré. / Crystallization of hydrates during oil production is a major source of hazards, mainly related to flow lines plugging after hydrate agglomeration. During the petroleum extraction, oil and water circulate in the flow line, forming an unstable emulsion. The water phase in combination with light hydrocarbon components can form hydrates. The crystallization of hydrates has been extensively studied, mainly at low water content systems. However, as the oil field matures, the water fraction increases and can become the dominant phase, a system less known in what concerns hydrate formation. Actually, several techniques can be combined to avoid or remediate hydrate formation. Recently, a new class of additives called Low Dosage Hydrate Inhibitor (LDHI) started to be studied, they are classified as Kinetic Hydrate Inhibitors (KHI-LDHI) and Anti-Agglomerants (AA-LDHI).This work is a parametric study about hydrate formation from emulsion systems ranging from low to high water content, where different flow rates and the anti-agglomerant presence were investigated. The experiments were performed at the Archimède flow loop, which is able to reproduce deep sea conditions. The goal of this study is enhancing the knowledge in hydrate formation and comprehending how the dispersant additive acts to avoid agglomeration. For this matter, it was developed a crystallization topological model for the systems without and with additive. A technique to determine the system continuous phase and a mechanism of the anti-agglomerant action from the chord length measurements were also proposed.