The calcium region is currently a new frontier for modern shell model calculations, and detailed experimental data from these nuclei is critical for a comprehensive understanding of the region.Due to its very low natural abundance of 0.004%, the structure of the magic nucleus 46Ca has not been studied in great detail. Some excited states were previously identified by various reaction mechanisms, and few gamma rays were placed in the level scheme from results of beta-decay experiments equipped with limited detection capabilities. A high-statistics data set of the beta decay of the 46K 2- ground state into the excited states of 46Ca was measured with the GRIFFIN spectrometer located at TRIUMF-ISAC in December of 2014. A radioactive beam consisting almost entirely of 46K was implanted at the center of the GRIFFIN array, and the emitted gamma rays were detected by 15 high-purity germanium clover detectors. From forty hours of data collection, 430 million gamma-gamma coincidences were observed and analysed to construct the 46Ca level scheme. In total, 194 gamma rays were identified and placed into the level scheme; 150 of these transitions were observed for the first time. Angular correlations between pairs of gamma rays were analysed to investigate the spin assignments of the observed excited states. Correlations were investigated for 18 of the 42 observed excited states, and it was possible to confirm 7 previously reported spin assignments, and assign 3 new spins of 3-, 2-, and 3- for the 4435, 5052, and 5535 keV states, respectively. The measured half-life of the 96.41(10) s is in agreement with previous results. From the observed beta feeding intensities of this work, it is suggested that the 46K 2- ground state may contain more proton s1/2 character than has been previously believed. This is due to the strong population of the 5052 keV 2$^-$ state and the absence of observed feeding to the 46Ca ground state.
Cytochrome P450cam (a camphor hydroxylase) isolated from soil bacterium Pseudomonas putida shows potent importance in environmental applications such as the degradation of chlorinated organic pollutants and insect control agents. Introducing such chemicals can be hazardous to the environment due to their lack of biodegradation. In this thesis, I have studied the role of several P450cam mutants in the oxidation of 3-chloroindole to isatin and the role of wild type P450cam in the dealkylation of 1,4-dibutoxybenzene, a potent feeding-deterrent against stored product pests. Mutant (E156G/V247F/V253G/F256S) was the most active in the conversion of 3-chloroindole by P450cam. We propose two mechanisms for the dechlorination of 3-chloroindole by P450cam. To investigate structure-activity patterns of 1,4-dialkoxybenzenes against beetles, the octanol-water partition coefficients of selected dialkoxybenzenes were investigated. Furthermore, P. putida strain ATCC17453 was able to metabolize 1,4-dibutoxybenzene. Results revealed that cytochrome P450cam catalyzed the first and second dealkylation steps in the biodegradation mechanism.
Ruthenium-based anticancer compounds have become a leading area of development in medicinal chemistry. Ru(III) complexes, such as the antimetastatic compound imidazolium [trans-RuCl4(1H-imidazole)(DMSO-S)] (NAMI-A), where DMSO = dimethyl sulfoxide, have shown promising results in clinical trials. Furthermore, reports of organometallic Ru(II) arene complexes, such as [RuCl2(η6-p-cymene)(pta)] (RAPTA-C), where pta = 1,3,5-triaza-7-phosphatricyclo[188.8.131.52,7]decane, demonstrate that these types of compounds also have excellent chemotherapeutic potential. In this work, three families of new bimetallic drug candidates based on these types of Ru anticancer compounds have been developed, with the goal of generating multifunctional complexes with new biological activities. The first type of complex is ferrocene-functionalized pyridine analogues of NAMI-A. Inclusion of ferrocene generates bifunctional complexes with cytotoxicity from the ferrocene groups and antimetastatic activity from the Ru center. The second family of complexes described in this work is analogues of RAPTA-C with the pta ligand replaced with ferrocene-functionalized pyridine, imidazole, and piperidine ligands. These compounds have strong anticancer and antibiotic activities, which correlate quantitatively with the reduction potential of the ferrocene centers, implicating generation of reactive oxygen species as the origin of activity. The third family of complexes, asymmetric bimetallic complexes comprised of a Ru(III) NAMI-A-type center coupled to Ru(III) DNA intercalating groups via pyrimidine, have been synthesized. Functionalization with dipyrido[3,2-a:2’, 3’-c]phenazine (dppz) in particular led to strong DNA interactions and high cytotoxic activity. In this work, electron paramagnetic resonance (EPR) and NMR have been used to study the ligand-exchange processes of the complexes and their interactions with proteins. In particular, NMR was used to investigate the complicated solution behavior of NAMI-A. Furthermore, NMR studies of the complex with human serum albumin and human serum transferrin indicate non-specific coordination to histidine residues and changes in ligand exchange kinetics due to protein interactions.
The ability to predict the electrochemical performance of the catalyst layer (CL) in polymer electrolyte fuel cells (PEFCs) hinges on a precise knowledge of the water balance. The key effective properties of this layer, like gas diffusivity and vaporization exchange rate constant, control water distribution and fluxes in the complete cell. Unfortunately, the knowledge of relevant properties of CLs is rare and not available with sufficient accuracy. A physical model of water fluxes in CLs is proposed to develop a methodology for the determination of the effective properties of CLs. For the purpose of this work, the CL is considered exclusively as a medium for vapor diffusion, liquid water permeation, and vaporization exchange. The presented model exploits an analogy of the water transport problem to the processes involved in charge transfer in a porous electrode, which is represented by the famous transmission line model (TLM). The expectation is that this analogy could lead to a diagnostic tool with similar capabilities as electrochemical impedance spectroscopy (EIS) in rationalizing the response of CLs to varying conditions and in extracting parameters of water transport and vaporization exchange. An analytical solution under steady state and isothermal conditions is presented that rationalizes the relation between controlled environmental conditions and the net water flux under partial saturation. The analysis of water flux data using this solution provides a method for the extraction of the net vaporization exchange rate, the activation energy of vaporization, vapor diffusivity, and the temperature exponent of the vapor diffusivity, which allows the transport mechanism of vapor diffusion in the CL to be identified. Transient analysis with a periodic perturbation is then explored. The overall impedance of water transport and the response function of a voltage change to a vapor change are analyzed for a specific scenario, where no effluence of liquid water from the CL is permitted. The methodology based on the transient analysis provides not only a way to extracting the effective properties of the CL, but also a way to estimate the liquid saturation in the CL.
The production of renewable energy conversion devices is crucial in reducing greenhouse gas emissions and sustaining the energy required for future generations. However, most energy conversion devices currently available have high costs, which greatly slow down any transition from non-renewable combustion devices. The most promising low-cost, renewable energy conversion devices are based on anion-conducting membranes, such as those found in hydrogen fuel cells, water electrolyzers, redox flow batteries, and electrodialysis. Unfortunately, the current lifetime of such devices is too short for wide-spread adoption. The main issue is the instability of the alkaline anion exchange membrane towards caustic hydroxide. While a significant amount of research has been on demonstrating materials that have longer lifetimes, little work has been concentrated on investigating the degradation pathways on small molecule model compounds. By understanding the chemistry behind their weakness, materials can be specifically designed to counter such pathways. This then leads towards specifically designed polymers with high endurance. The development towards permanently-stable, alkaline anion exchange membranes is the focus of this thesis. Throughout this thesis, new model compounds are developed and extensively characterized. Using new stability tests, the degradation pathways are identified and the stability is quantitatively compared. Novel polymers are then prepared, which are designed to mimic the highest stability small molecule compounds. Steric hindrance is found to be the most promising method towards durable cationic polymers. From Chapter 2 to Chapter 5, the prepared materials become more and more resistant to hydroxide, demonstrating development in the correct direction.
Access to new and rare radioactive isotopes is imperative for establishing fundamental knowledge and for its application in nuclear science. Rare Isotope Beam (RIB) facilities around the world, such as TRIUMF, work towards development of new target materials to generate increasingly exotic species, which are used in nuclear medicine, astrophysics and fundamental physics studies. At Simon Fraser University and TRIUMF, a computer simulation of the RIB targets used at the Isotope Separation and ACceleration (ISAC) facility of TRIUMF was built, to compliment existing knowledge and to support new target material development. The simulation was built using the GEANT4 nuclear transport toolkit, and can simulate the production rate of isotopes from user-defined beam and target characteristics. The simulation models the bombardment of a production target by an incident high-energy particle beam and calculates isotope production rates via fission, fragmentation and spallation. In-target production rates from the simulation were analysed and compared to production mechanisms within the simulation environment, other nuclear transport algorithms and to the experimentally measured yield rates from the ISAC yield station. Additionally, preliminary studies were conducted using these in-target production rates as illustrative examples, showing the capabilities and power of the simulation.
The purpose of the present work is to investigate the factors affecting antibody immobilization, and antibody-antigen interactions on a microfluidic chip. The results of this study will be utilized for the development of a microfluidic antibody bioarray for detection of two target proteins. Two interleukins of diagnostic value have been selected: Interleukin-6 (IL-6), and Interleukin-2 (IL-2). The micromosaic array is used for detection of IL-2 and IL-6 on a microfluidic chip. This method is used to optimize a variety of factors that affect antibody immobilization on the surface of a microfluidic chip, as well as bioarray conditions for enhancement of signals. Surface Plasmon Resonance (SPR) spectroscopy is used to obtain the association and dissociation rate constants for antibody-antigen binding in this work.
The work presented in this thesis examines the design, preparation and evaluation of light controlled biologically inspired small molecules. Incorporation of light sensitivity was achieved through the introduction of a photoresponsive diarylethene group, into a specific position within the molecular structure of a biologically relevant compound. The diarylethene class of photoresponsive molecules can absorb light of a specific wavelength, and subsequently undergo a reversible, light induced isomerization reaction, to generate a new structure with a unique set of chemical and physical properties. This photoisomerization process, also referred to as photoswitching, allows for reversible manipulation of the modified biomolecule’s properties, and consequently its ability to interact with a target using light. During this thesis, two examples utilizing the diarylethene framework are presented as a means to control the properties; either geometric (steric) or electronic, of photoresponsive small molecules using light energy. In the first example, featured in Chapter 2, light is used to alter the binding affinity (and thus inhibitory potency) of a photoswitchable enzyme inhibitor. The design relies on the structural and geometrical changes that accompany photoswitching of the central diarylethene to achieve this. A series of inhibitor candidates, based on the bisindolylmaleimide class of protein kinase inhibitors, were synthesized and investigated. A number of challenges were encountered during the design process, including the poor photochemical performance and limited aqueous stability of the inhibitor candidates. Although, during the course of the project, two light controlled inhibitors with differing inhibition mechanisms were discovered. One derivative exhibited good in vitro inhibition, and its inhibitory activity could be switched from an inactive, “off” state, to an active, “on” state, with brief exposure to non-damaging visible light. A second derivative, self-assembled into large aggregate particles and interestingly, exhibited light dependent (more specifically, structure dependent) solubility in aqueous media. The aggregates were found to inhibit enzyme function in vitro, although through a non-specific adsorption mechanism. The aggregate assembly could be disrupted with exposure to visible light, which generated the water soluble isomer, and restored enzyme activity. In the second example, featured in Chapter 3, light is used to control the electronic properties of a photoisomerizable Pyridoxal 5’-phosphate (PLP) mimic and influence the rate of a racemization reaction. The design combines the essential structural features of PLP, which are an aldehyde and a pyridinium, with a diarylethene photoswitch. The inherent changes that take place to the structure of the diarylethene with photoisomerization, effectively allowed for reversible modulation of the degree of electronic connection between the aldehyde and pyridinium. Consequently, control over the cofactor mimic’s reactivity towards substrate was possible. In the inactive state, communication between the pyridinium and aldehyde are minimal, and as a result, the ability to convert a substrate to product is poor. Whereas in the active state, the extended communication pathway formed between the pyridinium and aldehyde, lead to a more efficient catalyst for substrate conversion.
This thesis describes efforts to introduce new redox reactivity into two classes of dioxygen-activating enzymes. First, I investigated modified cytochrome c peroxidase (CcP). Here, a series of Trp residues were introduced between the heme active site and the surface of the enzyme to serve as a hole transfer wire. The addition of two mutations (A193W and Y229W) introduced new oxidation chemistry to CcP, as evaluated using aromatic substrate oxidation assays. This enzyme is a functional model for lignin peroxidase enzymes and provides a strong foundation for the development of new protein-based oxidation catalysts. Second, we investigated cyanobacterial aldehyde deformylating oxygenase (cAdo) enzymes. Here, we characterized and investigated three Ru-cAdo models. To provide the four electrons required for catalysis, we introduced a Ru-tris(diimine) photosensitizer to solvent exposed cysteine residues. Through NMR and GC-MS, we gained an insight into the catalytic activity of Ru-cAdo. This work highlights the nature of protein based electron transfer and points toward other underlying factors that dictate catalytic efficiency.
Piezo-/ferroelectrics form an important class of functional materials that can transduce mechanical energy to electrical energy and vice versa. They have large impacts in medicine (ultrasound imaging), in naval exploration/defence (sonar) and in consumer products (random access memories, capacitors). Currently, there is high interest in the development of new lead-free materials due to health and environmental risk factors of high-performance lead-based materials, such as Pb(Zr,Ti)O3. One promising lead-free system is the (K,Na)NbO3 (KNN) solid solution, as it has a high Curie temperature, which allows for a wide operating temperature range for devices. In order to better understand the structure and property relations, single crystals are needed. In this work, single crystals of K0.1Na0.9NbO3 (KNN) and 0.98K0.8Na0.2NbO3 – 0.02LiNbO3 (KNN-LN) have been grown using a high-temperature solution growth method with K2CO3 and B2O3 as flux. Polarized light microscopy was used to study the Na-rich KNN crystals, and the phase diagram on the Na-rich end of the (1-x)KNbO3 - xNaNbO3 solid solution has been updated. With the intention of addressing the issue of composition segregation, a modified vapour transport equilibration technique has been developed and demonstrated to be a viable approach to increase the Li-content in the KNN-LN crystals. In addition, a new ternary solid solution of y(K0.5Na0.5)NbO3 – (1-y)[(1-x)Bi0.5K0.5TiO3 – xBaTiO3] has been synthesized in the form of ceramics with compositions of y = 0.96 to y = 0.98 and its partial phase diagram has been established. Aside from KNN-based materials, translucent ceramics of (1-x)(Na0.5Bi0.5)TiO3 – xAgNbO3 (NBT-AN) and (1-x)(Na0.5Bi0.5)TiO3 – xAgTaO3 (NBT-AT) have been successfully prepared via a solid state method under ambient pressure. The dielectric permittivity as a function of temperature is found to be constant for compositions of x > 0.12 (e.g. its variation is within ±10 % for both NBT-AN and NBT-AT (x = 0.16) between 0 °C and 350 °C), while the polarization versus electric field relation shows pure capacitive behaviour up to 250 °C. With these properties, NBT-AN and NBT-AT are promising candidates for electro-optics and/or high-temperature capacitors.