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

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DNA Repair by DNA with Visible Light: Investigations and Implications

Author: 
Date created: 
2017-04-27
Abstract: 

The DNAzyme UV1C was selected previously on the basis of its ability to utilize UV-B light to catalyze the repair of a cis-syn cyclobutane thymine dimer in which no phosphodiester linkage exists between the dimerized thymines. Systematic replacement of each of nine guanines in and around the active site by the guanine analog 6-MI allowed the expansion of the photocatalytic cross section throughout the UV-A and to the edge of the visible. The behaviour of these mutants fell into 3 classes. In one class, replacement of guanines in the quadruplex did not disrupt the wild-type activity. In another class, quadruplex positions, when replaced with 6-MI, led to a decrease in activity in the UV-B but new activity in the UV-A, providing strong evidence for exactly which guanine residues are catalytic in the DNAzyme. Most surprisingly, the G-23 position, thought to be near the active site but not catalytic in UV1C, when replaced with 6-MI, leads to a full retention of activity in the UV-B with the strongest gain of activity in the UV-A. Further modifications to the G-23 position pushed its activity to maximize in the visible, but also ultimately disrupted the quadruplex-dependent activity in the UV-B. While selected against a model thymine dimer substrate, the DNAzyme is also shown to have photocatalytic activity on a bona fide DNA substrate. The continuity of the natural DNA substrate allows us to measure for the first time the effect of the UV1C DNAzyme on the rate of both thymine dimer formation as well as the rate of repair. When compared to double-stranded and single-stranded controls, at its photostationary state, UV1C leads to an overall reduction in fraction of dimerized thymines. Surprisingly, UV1C catalyzes both the repair and formation of thymine dimers in natural DNA, but more slowly than the model substrate that it was selected against. Together, these results shed further light on the emerging field of protein-independent thymine dimer repair. Arguments connecting the self-repair properties of DNA to the RNA world and prebiotic chemistry are offered.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dipankar Sen
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.

Understanding Milk Protein Adsorption as a Model to Study Sample Loss in Proteomics

Date created: 
2017-08-25
Abstract: 

Non-specific protein adsorption is one of the causes of sample loss in biological experiments. This is a cause of concern in studies where samples are complex and many of the constituent proteins are low abundant, unquantified or unidentified. Since the proteins are irreversibly lost from the samples, it eludes their detection and their role in biological systems cannot be ascertained. This sample loss is unpredictable and non-reproducible which leads to distorted data. On an industrial scale, non-specific adsorption of proteins on machinery may reduce the machine’s efficiency and life. Similarly, unaccounted sample loss due to adsorption during storage contributes to transmission losses to the manufacturer. Various external factors affect protein adsorption that can be exploited to reduce sample loss. In this work, we studied milk proteome adsorption and attempted to quantify the effect of three prominent external factors on the differential adsorption pattern of milk proteins. For this project, we optimized an in-house developed DPA method based on SDS-PAGE, which not only is tag-less and MS compatible but also fast and economical.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Bingyun Sun
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.

Heme-utilizing ribozymes and DNAzymes: Biological impacts, structural aspects, and a kinetic model of activation

Date created: 
2017-08-17
Abstract: 

Guanine-rich RNAs and DNAs that fold into guanine quadruplexes are found to complex tightly with porphyrins such as hemin [Fe(III)-heme]. The generated complex displays robust peroxidase (1 e- oxidation) as well as peroxygenase (2 e- oxidation) activity, greater than that of disaggregated heme itself. They can, thus, be regarded as heme-Utilizing DNAzymes and ribozymes. The folded DNAzymes appear to provide a unique chemical environment to the bound heme that by analogy resembles that of hemoproteins such as horseradish peroxidase (HRP) and cytochrome P450s. This work focuses on three aspects of these ribozymes and DNAzymes. First, we demonstrate that “toxic”, guanine-rich RNAs that accumulate in the cytoplasm of neurons afflicted with the familial forms of two neurodegenerative diseases: Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD), and are indeed thought to be causative of those diseases, efficiently bind and activate heme. Second, we systematically investigate the special status (or not) of guanine quartets in DNA/RNA for the purpose of binding and activating heme. Specifically, we explore whether isoguanine-containing DNAs, which in the presence of certain cations (including Na+, Cs+ and NH4+) form isoG quintets, while in K+, they form isoG quartets, can also bind and activate heme. We make the important observation that while G-quartets and iG-quintets both bind and activate heme, iG-quartets do not. Evidence from the theoretical/computational literature provides a satisfactory explanation for this observation, which in turn helps to illuminate the key structural features of nucleic acids that are necessary for binding and activating heme. Finally, we carry out fast kinetic measurements (using a stopped-flow enabled UV-vis spectrophotometer) to study the identities and formation of hydrogen peroxide-generated activated heme species within the above DNA-heme complexes. With the aid of Pro-KIV software, we perform singular value decomposition and global fitting analysis to formulate with a kinetic scheme for heme activation by these DNAzymes.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dipankar Sen
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.

Development of a photo-controlled polymeric dry adhesive

Author: 
Date created: 
2017-08-28
Abstract: 

The work presented in this thesis describes the design, synthesis, and analysis of a polymeric donor-acceptor Stenhouse adduct (DASA). This photoswitch was chosen as it switches between two isomeric states, open and closed, that are neutral and zwitterionic respectively. The goal of this project was to manipulate this change in polarity to induce a stronger adhesive response in the polymer, due to an increase in the dipole-dipole interaction between the polymer and a contact piece. While the single molecule exhibits reversibility in solution, the polymer does not appear to reverse in solution or in the solid state. There was a change of 18° in the contact angle, indicating a photoinduced change in the intermolecular forces did occur, however this has no significant effect on the bulk adhesive properties.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Neil Branda
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.

Computational Studies of the Effects of Pressure on Reaction Kinetics and Reaction Mechanisms

Date created: 
2017-10-10
Abstract: 

Both experiment and first principles calculations unequivocally indicate that properties of elements and their compounds undergo a tremendous transformation at ultra-high pressures due to the fact that the difference between intra- and intermolecular interactions disappears under such conditions. Yet, even at much milder pressures, when molecules still retain their individual identity, their chemical properties and reactivity change dramatically. We propose a set of techniques, based on molecular dynamics simulations and quantum mechanical calculations, which can aid in the understanding and prediction of the behavior of chemical systems over a wide range of high pressures.Experimentally, the effects of pressure on reaction rates and equilibrium constants are described by their pressure derivatives, known as volumes of activation and reaction volumes respectively. These quantities are directly linked to partial molar volumes of reactants, transition states, and products. We formulate a molecular dynamics method for the accurate calculation of molecular volumes. This method can be applied to both stable and transient species, which makes it suitable for quantitative analysis of experimental volumes of activation and reaction volumes. The calculated partial molar volumes, as well as reaction and activation volumes obtained from them, agree well with experimental data. To assess the reliability of the experimental activation and reaction volumes, we also present an analysis of the most common empirical analytical functions used to obtain them from pressure dependences of the rate and equilibrium constants. Since mechanisms of chemical reactions are often described in terms of properties of their potential energy surfaces (PES) or Gibbs energy surfaces (GES), we present an analysis of pressure-induced deformations of GES of solvated reaction systems and use quantum mechanical and molecular dynamics simulations to construct energy surfaces and reaction profiles of compressed species, and to analyze how their shapes and topography change in response to compression. We also discuss the important role of volume profiles in assessing pressure-induced deformations of GES.

Document type: 
Thesis
Senior supervisor: 
Michael Eikerling
Noham Weinberg
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.

Towards stable polymer solar cells through crosslinking and sidechain cleavage

Author: 
Date created: 
2017-08-22
Abstract: 

This thesis focuses on the investigation of two strategies for stabilizing the photovoltaic performance of polymer solar cells. Polymer solar cells (PSC) fabricated using solution processable conjugated polymers offer the potential for high-speed production of solar cell modules at low cost. However, achieving high power conversion efficiency (PCE) and long lifetime remains a challenge for PSCs. Photoexcitation of a conjugated polymer generates tightly bound electron-hole pairs (i.e., excitons) that require an electron acceptor (e.g., fullerene) for the dissociation of excitons into free charges. An interpenetrating network of conjugated polymer and fullerene (i.e., bulk heterojunction) is ideal for efficient charge generation due to the existence of a high interfacial area. However, such a morphology is not thermodynamically stable and is subject to large phase segregation in the form of fullerene aggregation provoked by the build-up of excessive heat during the operation of PSCs. Consequently, the PCE of PSCs degrades over time. In this thesis, two strategies for morphological stabilization are investigated using derivatives of poly(benzo[1,2-b:4,5-b′]dithiophene-thieno[3,4-b]thiophene) (PTB). In one strategy, a derivative of PTB having thermally-cleavable tetrahydropyran (THP) sidechains (PTB(THP)) is synthesized. Removal of the THP sidechains by thermal annealing reduces the mobility of PTB, thus retarding the diffusion of fullerene through the polymer matrix to form large aggregates. Photovoltaic (PV) devices made from PTB(THP) after thermal-cleavage of the sidechains exhibited stable PCE over prolonged thermal annealing, which is attributed to the thermally-stable morphology observed by microscopic studies. In the second strategy, a series of PTB derivatives bearing photocrosslinkable chlorooctyl sidechains (PTB-Cl) are synthesized. Photocrosslinking initiated by deep UV is able to insolubilize thin films of PTB-Cls. PV devices having stable PCE over prolonged thermal annealing were demonstrated using photocrosslinked PTB-Cls. However, high-number of photocrosslinkable sidechains and prolonged UV irradiation pose negative effects on the PCE and stability of PV devices made from PTB-Cls. In addition, accurate PCE measurement is of importance for the research of PSC. In Chapter 4, measurement errors of PCE using a simple xenon arc lamp are discussed. Improvements of measurement accuracy are demonstrated following simple modifications of the instruments and the measurement procedure.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Steven Holdcroft
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.

Time-resolved gamma-ray spectroscopy with the GEARS detector: Applications in environmental radionuclide monitoring and neutron activation analysis

Date created: 
2017-08-17
Abstract: 

The Simon Fraser University Nuclear Science Laboratory (SFU NSL) joined into two collaborations, each with an interest in monitoring Fukushima-derived cesium-134 and cesium-137 in various environmental samples. The first investigated Fukushima-derived contamination in soil and three species of Pacific salmon, sockeye, chum, and Chinook. The second investigated Fukushima-derived contamination in sockeye salmon, Dungeness crab, and kelp. In both of these monitoring campaigns, the maximum radiocesium activity concentrations observed were significantly below Health Canada's regulatory limits with the conclusion drawn that there is no health risk to the average Canadian seafood consumer. The Neutron Generator Facility at SFU NSL has recently acquired a Thermo Scientific P 385 neutron generator capable of activating samples, inducing radioactivity in them which may be studied via time-resolved gamma-ray spectroscopy. Recording timing information is a prerequisite of these studies therefore, a new data acquisition (DAQ) system was installed with the Germanium detector for Elemental Analysis and Radioactivity Studies enabling timing measurements to take place. The new DAQ system was benchmarked via the measurement of two neutron activated metals, verifying its stability and precision.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Krzysztof Starosta
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) M.Sc.

Exploring gold(I) as a luminophore for emissive coordination polymers

Author: 
Date created: 
2017-07-27
Abstract: 

This thesis focuses on the incorporation of gold(I) as a luminophore in photoluminescent materials via coordination polymer (CP) methodology. This is explored via two avenues: (i) the use of dicyanoaurate, [Au(CN)2]– as a building block with lanthanide metals and (ii) the design of electron-rich gold(I) building blocks containing the ‘aurothiolate’ motif. A series of dicyanoaurate/lanthanide CPs [nBu4N]2[Ln(NO3)4Au(CN)2] (LnAu) Ln = Ce, Nd, Sm, Eu, Gd, Tb, and Dy were synthesized. LnAu CPs are strongly luminescent at room temperature and this behaviour is primarily lanthanide-based. These results contrast those reported for Ln[Au(CN)2]3·3H2O (LnAu3), which is only faintly emissive at room temperature. Solid-solutions of Eu(III)/Tb(III) were prepared to explore these differences. The emission colour in LnAu could be varied between red and green corresponding to Eu/Tb ratio, whereas in LnAu3 only red Eu(III) emission is observed. Short Ln–Ln contacts in LnAu3 enable energy transfer, whereas in LnAu the long Ln–Ln distances preclude this, allowing for colour tunable emission. Colour tuning was explored to find the maximum available gamut, and it was found that white emission, and multiple emission colours is possible at room temperature. Design considerations for an electron-rich gold(I) building block were evaluated and the dithiocarbmate building block [Au2(dopdtc)2] was synthesized. The would-be building block is hindered in its ability to form CPs but its luminescence proved to be interesting; the pressure dependent emission energy is significantly lower than for similar materials, despite similar Au–Au distances. The role of geometry becomes clear when probed using DFT; deviations from linearity in aurophilic chains result in the transition becoming MLCT in nature, which is less sensitive to applied pressure. To improve the utility of an electron rich Au(I) building block, [Au2(i-mnt)2]2– (i-mnt = S2C=C(C#N)22–) was explored for its ability to form intermolecular aurophilic interactions. Aurophilic materials were prepared via substituting [nBu4N]+ cations with those containing the N-H+ functional group, illustrating that [Au2(i-mnt)2]2– is a good candidate for aurophilic CPs. To that end, some preliminary results in the preparation of [Au2(i-mnt)2]2– CPs are reported.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Daniel Leznoff
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.

Water permeation through polymer electrolyte membranes

Author: 
Date created: 
2017-07-26
Abstract: 

Water management has a major impact on the performance of the polymer electrolyte membrane fuel cells. An understanding of water permeation through polymer electrolyte membranes is crucial to offset the unbalanced water activity within fuel cells. The work presented in this thesis includes contributions that provide insight into internal and interfacial water permeation behavior of membranes, as well as insight into how membranes could be designed to enhance water management. Three types of ex-situ water permeation techniques are used in this thesis work. These are: liquid-liquid water permeation (LLP) in which both sides of the membrane are in contact with liquid water; liquid-vapor permeation (LVP) where one side of the membrane is exposed to liquid, and the other is exposed to vapor; and vapor-vapor permeation (VVP) where both sides of the membrane are exposed to water vapor. Three polymer electrolyte membrane systems were investigated under varied experimental conditions: degraded Nafion®, short side chain (SSC) perfluorosulfonic acid ionomer membrane, and an emerging class of anion exchange membrane, poly(benzimidazolium). Correlations between membrane series were drawn and compared to the commercially-available materials. It was found that membranes of smaller thickness, greater water volume fraction (Xv), and higher ion exchange capacity (IEC) result in a higher overall water permeability. However, the membrane thickness, Xv, and IEC do not dominate the rate of water permeation through the membrane interface. In contrast, the side chain length of the polymer is found to influence the interfacial water permeation, wherein membranes with longer side chain length are more water permeable at the interface.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Steven Holdcroft
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.

Synthesis of natural and unnatural products by elaboration of alpha-chloroaldehydes

Date created: 
2017-04-21
Abstract: 

Fitting broadly under the category of target-oriented synthesis of complex organic molecules, the work described in this document pertains primarily to exploiting the facile organocatalytic synthesis of enantiomerically enriched α-chloroaldehydes, drawing out their potential through conversion into 1,2-chlorohydrins, and exploring the means by which these substances may be coerced to undergo intramolecular cyclization involving a nitrogen nucleophile. Specific targets and methodology include a successfully completed synthesis of the natural product (+)-preussin and similarly substituted pyrrolidines through the reductive annulation of β-iminochlorohydrins, a formal synthesis of (-)-swainsonine and related alkaloids through a related intramolecular cyclization strategy, and the synthesis and structural analysis of a carbocyclic mechanism-based inactivator of a glycoside hydrolase. As a secondary focus, this thesis also describes the isolation, structural elucidation, and testing of the long-range sex pheromone of the strepsipteran Xenos peckii, which was ultimately determined to be (7E,11E)-3,5,9,11-tetramethyltridecadienal, and of the chemical constituents of the bed bug (Cimex lectularius) aggregation pheromone, which were ultimately determined to be dimethyl disulfide, dimethyl trisulfide, (E)-2-hexenal, (E)-2-octenal, 2-hexanone, and histamine.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Robert Britton
Department: 
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.