Chemistry - Theses, Dissertations, and other Required Graduate Degree Essays

Receive updates for this collection

Co(III) Complexes as Pro-drugs for Cancer Therapy

Author: 
File(s): 
Date created: 
2016-05-13
Supervisor(s): 
Tim Storr
Charles Walsby
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.
Abstract: 

Cancer is the leading cause of death in Canada and is characterized by irregular and uncontrolled cell growth. In many cases this uncontrolled cell growth results in a solid mass of cells called a tumor. When the inner part of a tumor is sequestered from blood vessels, the nutrient and oxygen levels decrease. The term “hypoxia” is used to describe low oxygen level in tissue. Hypoxia induces more reducing conditions in a tumor in comparison to normal tissue. The objective of this project was to generate a series of octahedral Co(III) complexes for the treatment of cancer. We designed pro-drugs that are initially administered to the body in an inactive form, and can be selectively activated under the hypoxic (reducing) conditions in tumors. In this work, a series of octahedral Co(III) salen complexes were synthesized incorporating 1-methylimidazole in axial positions. We investigated the stability of the complexes in solution, and the effect of different para-ring substituents on the Co(III) / Co(II) reduction potential. We concluded that the reduction potentials of the complexes were correlated with the electron donating ability of the para-ring substituents, and that a geometry change from octahedral to square-planar upon reduction leads to axial ligand release. Building on these results, coumarin fluorophores were then attached to the Co(III) complexes via a functionalized imidazole. We found that the fluorescence of the coumarin was largely quenched while bound to the Co(III) center. Ligand release was then studied in the presence of excess competing ligands and in the presence of a reducing agent. Our results suggest that both ligand exchange and reduction play a role in axial ligand release in these systems.

Document type: 
Thesis

Synthesis and evaluation of novel carbocyclic carbohydrate analogues

File(s): 
Date created: 
2016-04-15
Supervisor(s): 
Robert A. Britton
Andrew J Bennett
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.
Abstract: 

Carbohydrate analogues play an indispensible role in the study of glycan processing enzymes. These compounds have attracted attention as probes of enzyme mechanisms, as chemical tools for the elucidation of enzyme function and as potential pharmaceuticals. The development of organocatalytic aldol chemistry has fundamentally altered the way chemists approach the synthesis of carbohydrate analogues. In this thesis I highlight a novel strategy toward the synthesis of carbocyclic carbohydrate analogues which utilizes a proline-catalyzed aldol reaction and a metal-catalyzed carbocyclization as key steps. This strategy was successfully implemented in the synthesis of an ensemble of galactose and N-acetylgalactosamine analogues. Furthermore, I present preliminary results toward the biological evaluation of these compounds.

Document type: 
Thesis

The Photochromism of a Diester Linked Bisanthracene

Author: 
File(s): 
Date created: 
2016-04-15
Supervisor(s): 
Vance Williams
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.
Abstract: 

A bisanthracene diester was synthesized in an effort to increase the rate of the anthracene photochemical dimerization. Preliminary reactions of the bisanthracene resulted in the formation of an intramolecular product that cyclizes across the 9, 10, 1’, 4’-position of the anthracenes. This results in an unsymmetrical dianthracene that possesses an isolated alkene group. The research in this thesis describes the photochromic properties of the bisanthracene, as well as studies into the reactivity of the isolated alkene. Different photochromic properties of the bisanthracene were investigated. The optimized conditions were found using a dilute solution in benzene while selectively exciting the bisanthracene. The addition of a peroxycarboxylic acid to the photoproduct resulted in the formation of an epoxide, which caused the intramolecular product to become more photochemically and thermally stable. This resulted in a locked state. Attempts to unlock this system by removal of the epoxide resulted in only low yields of the bisanthracene, but does represent a preliminary gated system for anthracene photochemical reaction.

Document type: 
Thesis

Development of an in vitro method to study heterogeneous particle mimic exposures

File(s): 
Date created: 
2016-04-12
Supervisor(s): 
George Agnes
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

Particulate matter, a heterogeneous mixture of solid and liquid particles suspended in the atmosphere, has been strongly linked to several respiratory diseases and cardiovascular disease. Due to its impact on human health, epidemiological, in vivo, and in vitro studies are used to assess toxicity of diverse types of particulate matter, and mechanisms behind disease pathogenesis. To enable insight on how particle composition affects cellular response, an in vitro dose-response apparatus and methodology were developed to deliver heterogeneous particles of controlled compositions onto human lung cell mono- and co-cultures. Silica particles, an ambient particle type sourced from crustal matter, were generated using the apparatus and were delivered onto cultures of alveolar epithelial cells (A549) up to an estimated 3.2 µg cm-2. No change was observed in membrane bound protein intercellular adhesion molecule-1 (ICAM-1) expression. In a proof of concept study, tumor necrosis factor (TNF)-α, a potent cytokine, was introduced as a secondary component to silica. This binary particle type was also delivered onto A549 monocultures, and ICAM-1 signal increased with an increase in dose. Silica particles were also delivered onto co-cultures containing A549 cells and macrophages differentiated from blood monocyte cells (THP-1). Cytokine interleukin (IL)-6 was significantly up-regulated in co-cultures, but IL-8 was not. Lipopolysaccharide (LPS), a component of the cell wall in Gram negative bacteria, and nickel, in the form of Ni(NO3)2·6H2O, were introduced as secondary components to silica. These binary particle types were generated at ratios representative of respirable agricultural soils and dosed onto co-cultures. It was observed that silica plus LPS particles caused an up-regulation of IL-6 and IL-8 response relative to silica particles, whereas silica plus nickel particles did not. LPS bioavailability was determined as 10±3% and 1.0±0.6% for silica plus LPS particles at atmospherically-relevant LPS to silica mass ratios of 91 ppm and 910 ppm, respectively. The reduction in bioavailability showed how interactions between compositions in a heterogeneous particle type can affect cellular response.

Document type: 
Thesis

Investigations into O-GlcNAcylation through analytical mass spectrometry

Author: 
File(s): 
Date created: 
2014-12-17
Supervisor(s): 
David Vocadlo
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.
Abstract: 

The modification of proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is found on many proteins in the nucleus and cytoplasm. O-GlcNAc has been implicated in many physiological processes but much remains to be learned about the effects of this modification on protein function. In this thesis I detail two studies aimed to improve our understanding of protein modification by O-GlcNAc. First, I describe a bioinformatics study focused on uncovering the protein structural features that favour O-GlcNAcylation by the enzyme O-GlcNAc transferase. The search for a sequence or structural motif to be found amongst the many substrates O-GlcNAcylated by OGT is a path well-trodden. On the basis of our analysis of site mapping data accumulated from the literature and also through targeted site mapping of an entirely intrinsically disordered protein by mass spectrometry, I counter argue that OGT preferentially targets substrates which can be intrinsically disordered.Second, I describe a study aimed to gain insight into cellular proteomic response due to lowering of O-GlcNAc levels. There is mounting evidence O-GlcNAcylation is both linked with protein folding and intracellular proteome stability. While stability is measured by turnover it is also tied to misfolding. We investigated a possible relationship between lowered O-GlcNAc levels and instability of a segment of the proteome using stable isotope labelling by amino acids in cell culture mass spectrometry.

Document type: 
Thesis

New approaches to remediation of nanoscale contaminants in the workplace

File(s): 
Date created: 
2014-12-15
Supervisor(s): 
Byron D. Gates
Department: 
Science: Chemistry
Thesis type: 
(Thesis) M.Sc.
Abstract: 

It is important that all workers understand the health and safety risks of their work environment. It has been demonstrated that exposure to nanoparticles can lead to potential health concerns. A 1 mL nanoparticle solution spill can contain >10^9 nanoparticles, with the particles invisible to the human eye. This nanoparticle spill can cause further contamination in the work environment as workers transfer the particles from one area to another if the nanoparticles are not properly remediated. Therefore, it is essential that effective methods be developed for early identification and clean-up of such spills to avoid potential hazards to those working with these particles. One goal of this research is to develop a methodology that is simple to implement on a global scale to rapidly detect the presence of nanoparticles in different workplace environments to accompany methods for the remediation of spills containing nanoparticles. X-ray fluorescence spectroscopy was identified as a portable solution to potentially identify the presence of and the extent of a spill containing nanoparticles. Many other techniques could also be utilized, but the ease of use at the point of contamination without the requirement of sample preparation makes this an attractive solution in nanoparticle remediation. Another goal of this research is to develop an efficient, effective and inexpensive means to remediate spills containing nanoparticle contaminants. The implementation of these remediation procedures would change how nanoparticles are treated in the workplace and promote a healthy work environment when using materials that would otherwise go unnoticed due to their small size. Remediation of nanoparticles spilled in the workplace requires a method of acknowledging that these unseen particles are appropriately being removed and to avoid spreading these particles to a wider extent throughout the workplace. Analytical techniques were used to monitor the presence of nanoparticle contaminants and, in combination with techniques to encapsulate nanomaterials within a spill, were used to assess the appropriateness of these remediation techniques for cleaning up simulated spills. These studies demonstrate a series of methods to progressively remove nanoparticle contamination from countertops in the workplace.

Document type: 
Thesis

Establishing the Quality of Molecular Coatings on Gold Nanoparticles

Author: 
File(s): 
Date created: 
2014-12-16
Supervisor(s): 
Byron D. Gates
Department: 
Science:
Thesis type: 
(Thesis) Ph.D.
Abstract: 

The surface chemistry of nanoparticles imparts colloidal stability to nanoparticles by acting as barriers between their surrounding environment and the nanoparticles. Gold nanoparticles (AuNPs) are an ideal platform for many studies because of localized surface plasmon resonant properties, chemical stability, and the relative ease of modifying their surfaces with a wide variety of molecular coatings (e.g., alkanethiolates). Understanding and improving the physicochemical stability of these surface-modified nanoparticles is essential for their reproducible use in each application. The long-term colloidal stability of AuNPs relies on the resistance of their surface modifications to thermal degradation, chemical attack and oxidizing conditions. For this purpose, my research has been focused on determining the quality of molecular coatings on gold nanoparticles, and developing techniques, which are complementary to each other, to assess the quality factor of these coatings. Gold nanoparticles with varied qualities of molecular coatings were prepared and tested for their relative stabilities under various physical (e.g., temperature, time, laser irradiation) and chemical (e.g., in presence of metal etchants) conditions. We found that the quality of molecular coatings on AuNPs depends on the process conditions such as solution composition (e.g., the presence of co-surfactants, concentration of excess surfactants), density of capping molecules, and process time, used to form these coatings. We found that higher quality molecular coatings on the gold colloids increased the chances that the particles would remain stable over the over the duration of their intended use. Those colloids modified with relatively higher quality self-assembled monolayers were also more resistant to cyanide etching. These results highlight the importance of methodology for preparing high quality monolayers on nanoparticles and testing their ability to remain stable over the duration of their intended use, for example, during photothermal processes. In addition, the loading of DNA molecules onto AuNPs was tuned to achieve varying densities of DNA, and through this work, achieved the highest reported loading of single-stranded DNA (ss-DNA) molecules on gold nanorods. These high loadings of DNA oligonucleotides could enable a high loading of therapeutics onto the nanorods, which could translate into a higher or more prolonged delivery of therapeutic doses when actived by photothermal or other processes.

Document type: 
Thesis

Study of Complex Ferroelectric and Antiferroelectric Systems

Author: 
File(s): 
Date created: 
2014-12-12
Supervisor(s): 
Zuo-Guang Ye
Department: 
Science: Chemistry
Thesis type: 
(Thesis) Ph.D.
Abstract: 

Rhombohedral (R), monoclinic (MA/MC) and tetragonal (T) phases are found in coexistence in a compositionally segregated xPb(In1/2Nb1/2)O3- yPb(Mg1/3Nb2/3)O3- zPbTiO3 (PIN-PMN-PT) (nominal composition x/y/z = 30/35/35) single crystal. Polarized light (PLM) measurements and X-ray diffraction (XRD) on both single crystal and ceramic series confirms the existence of 2 different monoclinic phases. A phase diagram in the MPB region of the PIN-PMN-PT solid solution is proposed based on both single crystals and ceramic material.Further study on the temperature driven rhombohedral (R) (R3m)  monoclinic (MA) phase transition in the single crystals and ceramics with MPB composition are carried out. It was found that the rhombohedral domain is able to return to its original state after annealed at above the RMA phase transition temperature (TR-M) but below the Currie temperature (TC). A polarization reversal model is proposed based on the polarization rotation theory.Solid solutions of (1-x)Pb(Mg1/2W1/2)O3-xPb(M1/2W1/2)O3(M = Zn2+ and Mn2+) have been prepared by solid state reaction with composition x up to 30% for Zn and 50% for Mn. The influence of Zn2+ and Mn2+ on structure, electrical and magnetic properties are revealed. (1-x)PbZrO3-xPb(Mn1/2W1/2)O3 (x = 0 - 0.1) as another new solid solution system was also prepared by the solid state reaction method. Its crystal structure, dielectric properties and antiferroelectricity were investigated and it was proven to be an excellent candidate for energy storage devices.In summary, the study for PIN-PMN-PT ternary solid solution near its MPB composition shall provide a general guideline for designing high performance peizocrystals. The study of PZ-based and PMW-based antiferroelectric solid solutions provided better understanding of antiferroelectric perovskites and provides a different approach for the design of soft antiferroelectric material with high energy density.

Document type: 
Thesis

Studies toward the biosynthesis of chimonanthine in chimonanthus praecox

Author: 
File(s): 
Date created: 
2016-01-18
Supervisor(s): 
Robert Britton
David J Vocadlo
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.
Abstract: 

Chimonanthine is the building block of a series of natural products found in terrestrial plants including members of Psychotria in the family of Rubiaceae. Studies have shown that alkaloids containing the chimonanthine core display interesting analgesic, inhibition of melanogenesis, and anti-cancer activities. The goal of this study is to explore the precursor directed biosynthesis of chimonanthine and the enzymes involved in the biosynthesis of chimoanthine as well as to identify these enzymes for potential use as biocatalysts that can generate libraries of modified natural products. Herein we report the identification of a suitable plant containing these enzymes and demonstrate the feasibility of new assays by showing that feeding of plants with synthetic precursors leads to the production of labelled chimonanthine.

Document type: 
Thesis

Alternative Platinum Electrocatalyst Designs for Improved Platinum Utilization

File(s): 
Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2014-12-10
Supervisor(s): 
Byron Gates
Department: 
Science:
Thesis type: 
(Thesis) Ph.D.
Abstract: 

Platinum electrocatalysts are important for a number of low and zero-emission energy technologies, including low temperature fuel cells. For reactions such as oxygen reduction at a fuel cell cathode, poor kinetics and harsh operating conditions (which lead to catalyst degradation) dictate the use of large volumes of Pt for efficient electrocatalysis. This need for a large quantity of Pt increases the cost of the fuel cell and makes the technology too expensive to compete with petroleum based energy alternatives typically used in automotive applications. Improving the effective utilization of Pt enables the same performance to be achieved with a smaller mass of Pt. A more effective use of Pt can be achieved through the use of alternative catalyst layer designs. The work presented in this thesis demonstrates three novel Pt catalyst layer designs with the aim of improving the effective utilization of Pt for electrocatalysis. These designs include pure Pt ordered porous electrodes (Pt-OP electrodes), supported Pt nanoparticle ordered porous electrodes (support@PtNP-OP electrodes) and nanobowl supported Pt NPs (support@PtNP nanobowls). These designs aim to enhance Pt utilization by improving: i) mass transport through the use of an open porous design; ii) Pt electrochemical stability via the use of stable materials throughout the electrocatalyst design and/or through support interactions; and iii) Pt catalytic activity via favorable interactions with support materials. The preparation of these new Pt electrocatalyst designs is presented through the use of sacrificial templates. The new materials were extensively characterized by electron microscopy, X-ray spectroscopy, and electrochemical methods. The alternative electrocatalyst designs demonstrated here provide new routes towards enhancing the utilization of Pt for electrocatalytic applications.

Document type: 
Thesis