• Stereoselective synthesis of substituted hexahydro-3a,4a-diazacyclopentaphenanthren-4-ones and aminoferrocenes

      Zaifman, Joshua David; Department of Chemistry (Brock University, 2011-05-17)
      This thesis explored the development of several methodologies for the stereoselective construction of ligand frameworks and some of their applications. The first segment concerns the application of an enantioselective lithiation at an Sp3_ hybridized position adjacent to nitrogen by means of the widely used and typically highly effective enantioselective lithiation with ( -)-sparteine. This investigation was intended to develop a method to install chirality into a system that would be converted into a family of diaminoylidenes for use as phosphine mimics in transition metal catalysis or as nucleophilic reagents. Molecular modeling of the system revealed some key interactions between the substrate and (-)-sparteine that provided general insight into the diamine's mode of action and should lend some predictive value to its future applications. The second portion focuses on the development of methods to access 1,2- disubstituted aminoferrocenes, an underexplored class of metallocenes possessing planar chirality. Two routes were examined involving a diastereoselective and an enantioselective pathway, where the latter method made use of the first BF3-mediated lithiation-substitution to install planar chirality. Key derivatives such as 1,2- aminophosphines, made readily accessible by the new route, were evaluated as ligands for Pd(II), Pt(II) and Ir(I). These complexes show activity in a number of transformations with both achiral and prochiral substrates. Optimization experiments were conducted to prepare enantiomerically enriched 2-substituted-I-aminoferrocenes by direct asymmetric lithiation of BF3-coordinated tertiary aminoferrocenes. A predictive computational model describing the transition state of this reaction was developed in collaboration with Professor Travis Dudding's group (Department of Chemistry, Brock University). The predicted stereochemistry of the process was confirmed by single-crystal X-ray analysis of a 2-phosphino-l-dimethylaminoferrocene derivative. Enantiomerically pure samples of the aminophosphine ligands derived from this new process have given promising preliminary results in the enantioselective hydrogenation of prochiral alkenes and warrant further stUdy in metal-mediated catalysis.

      Mansour, Hayam; Department of Biological Sciences (Brock University, 2012-06-04)
      Hepatitis C virus (HCV) is the causative agent of Hepatitis C, a serious global health problem which results in liver cirrhosis and hepatocellular carcinoma. Currently there is no effective treatment or vaccine against the virus. Therefore, development of a therapeutic vaccine is of paramount importance. In this project, three alternative approaches were used to control HCV including a DNA vaccine, a recombinant viral vaccine and RNA interference. The first approach was to test the effect of different promoters on the efficacy of a DNA vaccine against HCV. Plasmids encoding HCV-NS3 and E1 antigens were designed under three different promoters, adenoviral E1A, MLP, and CMV ie. The promoter effect on the antigen expression in 293 cells, as well as on the antibody level in immunized BALB/c mice, was evaluated. The results showed that the antigens were successfully expressed from all vectors. The CMV ie promoter induced the highest antigen expression and the highest antibody level. Second, the efficiency of a recombinant adenovirus vaccine encoding HCV-NS3 was compared to that of a HCV-NS3 plasmid vaccine. The results showed that the recombinant adenovirus vaccine induced higher antibody levels as compared to the plasmid vaccine. The relationship between the immune response and miRNA was also evaluated. The levels of mir-181, mir-155, mir-21 and mir-296 were quantified in the sera of immunized animals. mir-181 and mir-21 were found to be upregulated in animals injected with adenoviral vectors. Third, two recombinant adenoviruses encoding siRNAs targeting both the helicase and protease parts of the NS3 region were tested for their ability to inhibit NS3 expression. The results showed that the siRNA against protease was more effective in silencing the HCV-NS3 gene in a HCV replicon cell line. This result confirmed the efficiency of adenovirus for siRNA delivery. These results confirmed that CMV ie is optimum promoter for immune response induction. Adenovirus was shown to be an effective delivery vector for antigens or siRNAs. In addition, miRNAs were proved to be involved in the regulation of immune response.
    • Stretching the Vitruvian Man: Investigating Affective and Representational Arts-based Methodologies Towards Theorizing a More Humanistic Model of Medicine

      Couse, Candace; Interdisciplinary Humanities Program
      Westernized medicine can be said to illustrate its history and structure, as well as its current understanding of the capacity and appearance of the human through its visual representations of the body. Scientific images, this paper argues, become a site for interrogating the tangle of idealism, truth, objectivity and knowledge in how knowledge is actively used, replicated, paralleled and otherwise functions. First, asking how depictions of the medicalized body inform the epistemological foundations of medicine, and to what end, this work opens up the question of methodology, arguing that the integration of the modes of arts-based practices can bring medicine toward a much more realistic picture of the world. A parallel argument is a similarly concentrated interrogation of the affective quality of arts-based methodology, which is commonly understood to be the nucleus of work on the political dimensions of non-representational theory. I complicate the dominant scholarly preference for an ontologically rooted affect theory, finding it theoretically non-viable for art and humanistic medicine by thinking through subjectivity, autobiographical accounts of illness and epistemological flexibility. I see a path forward using a biologically and evolutionarily rooted affect theory, noting the ethical implications of its differences for a humanistic approach to medicine.
    • Structural, Magnetic and Thermal Studies of Ce1-xEuxCrO3 Nano-Powders

      Taheri, Maryam; Department of Physics
      A new series of nano-sized Ce1-xEuxCrO3 (x = 0.0 to 1.0) with an average particle size of 50 - 80 nm were synthesized using a solution combustion method. Nano-powders Ce1-xEuxCrO3 with the canted antiferromagnetic property exhibited interesting magnetic behaviours including the reversal magnetization and the exchange bias effect. The effect of europium doping as the ion with the smaller radius size and different electron con figuration on structural, magnetic and thermal properties of Ce1-xEuxCrO3 were investigated using various experimental techniques, i.e. DC/AC magnetic susceptibility, heat capacity, thermal expansion, Raman scattering, X-ray photoemission spectroscopy, transmission/scanning electron microscopy, X-ray powder diffraction and neutron scattering. An exchange bias effect, magnetization irreversibility and AC susceptibility dispersion in these samples confirmed the existence of the spin disorder magnetic phase in Ce1-xEuxCrO3 compounds. The exchange bias phenomenon, which is assigned to the exchange coupling between glassy-like shell and canted antiferromagnetic core, showed the opposite sign in CeCrO3 and EuCrO3 at low temperatures, suggesting different exchange interactions at the interfaces in these compounds. The energy level excitation of samples were examined by an inelastic neutron scattering which was in good agreement with the heat capacity data. Neutron scattering analysis of EuCrO3 was challenging due to the large neutron absorption cross-section of europium. All diffraction patterns of Ce1-xEuxCrO3 showed the magnetic peak attributed to the antiferromagnetic Cr3+ spins while none of the diffraction patterns could detect the magnetic ordering of the rare-earth ions in these samples.
    • Structural, Magnetic and Vibrational Studies of Entropy Stabilized Oxides

      Afsharvosoughi, Tahereh; Department of Physics
      The structural, magnetic and vibrational properties of high entropy oxide (HEO) and medium entropy oxides (MEOs) made from mixtures of five and four metal oxides were studied in this work. The HEO and MEOs obtained from solid state reactions in quinary and quaternary equimolar mixtures of oxides including ZnO, CuO, CoO, MgO and NiO which are called 5-HEO, 4-MEO(-Cu), 4-MEO(-Mg), 4-MEO(-Co), 4-MEO(-Ni) and 4-MEO(-Zn) in this thesis. The samples were sintered at high temperatures followed by air quenching. The x-ray diffraction measurements results show the formation of single rocksalt phase in all of them except 4MEO(-Ni). The magnetization measurements in zero field cooled (ZFC) and field cooled (FC) regimes under H=5000 Oe have provided strong evidence for long range magnetic ordering in 5-HEO and 4-MEOs. Two samples including 4-MEO(-Co) and 4-MEO(-Ni) exhibit high frustration factor which is a major component for spin glass phase. The AC susceptibility measurements for 4-MEO(-Co) and 4-MEO(-Ni) with the highest frustration factors have carried out in order to investigate the presence of spin glass. The segregation of Cu from the rocksalt phase in 5-HEO by resintering at intermediate temperature (700oC) was confirmed by x-ray diffraction measurements, SEM-EDS elemental mapping and magnetization measurements. Infrared refectance spectroscopy measurements (100-15000 cm-1) for 5-HEO and 4-MEOs with single rocksalt structures have revealed one strong mode and a weaker mode at lower frequency in the far infrared spectra. The Lorentz model and Kramers-Kronig (KK) analysis were implemented for the samples and the results were used in effective charge calculations which reveal that 4-MEO(-Cu) has the greatest ionic character whereas 4-MEO(-Mg) showed the least ionic character. The Raman spectroscopy which complements the infrared spectroscopy was carried out for 5-HEO and 4-MEOs. The results have indicated first and second order Raman modes in addition to a two-magnon mode at around 1600 cm-1 which was confirmed by studying the temperature dependence. While 4-MEO(-Co) also shows a peak near 1600cm-1 it is likely of different origin. In 4-MEO(-Cu) the two magnon scattering peak was not observed and it rather causes a high background which increases with decreasing temperature.
    • Structural, Magnetic, Dielectric, and Optical Properties of DyCrO3 and GeNi2O4 Materials

      Indovski, Biljana; Department of Physics
      GeNi2O4 is a cubic spinel with two antiferromagnetic transitions at low temperatures, while DyCrO3 has an orthorhombic perovskite structure with an antiferromagnetic transition at a higher temperature. Thin films of these compounds are widely researched for their applications in spintronics. The investigation of the structural, magnetic, dielectric, and optical properties of deposited thin films of these two materials can contribute to a better understanding of their physical characteristics which may lead to possible applications. In this research, DyCrO3 and GeNi2-xMgxO4 (x=0, 0.03) epitaxial thin films were deposited on SrTiO3 substrates using the pulsed laser deposition technique. As the c-lattice parameter of the orthorhombic DyCrO3 and a-lattice parameter of the cubic GeNi2O4 are almost having the same value, this is giving a rise to a small strain in their epitaxial thin films. Therefore, composite thin films of the DyCrO3 and GeNi2-xMgxO4 (x=0, 0.03) materials were also deposited. The structural properties of these thin films were examined using different X-ray techniques such as an X-ray diffraction, X-ray reflectivity, reciprocal space mapping, and in-plane pole figures. The results were analyzed to determine the preferred orientation, the thickness of the thin films, the presence of strain and defects, and the degree of epitaxy. The reciprocal space mapping results reveal a dependence between the thickness of the thin films and the presence of defects in the epitaxial films. The in-plane pole figure results show the presence of domains with different orientation in several thin films, although the results from the high-resolution X-ray diffraction indicate a single orientation in those films. The temperature dependence of magnetization in epitaxial thin films was measured in order to examine the magnetic anisotropy for the magnetic field normal and parallel to the surface of the films. These results indicate the presence of magnetic anisotropy in several thin films. GeNi2O4 is an interesting antiferromagnet as it has two closely spaced antiferromagnetic transitions that are the result of a spin reorientation in two types of {111} planes. Therefore, to better understand the ordering of the spins with respect to the {111} planes, additional measurements and analysis of the results were done on GeNi2O4 single crystals. The temperature dependence of magnetization was measured for the magnetic field applied parallel and perpendicular to the {111} planes. In addition, the temperature dependence of Raman spectra of a GeNi2O4 single crystal was measured and analyzed. These single crystal results of GeNi2O4 provide a better understanding of spin-phonon coupling and spin ordering and reorientation in this spinel compound.
    • A study of biting midge populations and an assessment of Bluetongue virus presence in southern Ontario, with a visual dichotomous key to the North American genera of Ceratopogonidae

      Jewiss-Gaines, Adam; Centre for Biotechnology
      Biting midges (Diptera: Ceratopogonidae) are flying insects that feed on blood in order to produce eggs. Due to their bloodfeeding habits, some species act as vectors for viruses, many of which affect ruminant animals. This establishes ceratopogonids as possible threats to livestock farmers, and therefore it is important to understand their distribution and habits. This study focussed on collecting biting midge specimens from localities across Ontario where livestock farms are present, and determining if they were carrying Bluetongue virus (BTV). Fourteen livestock farms were sampled to assess presence of ceratopogonid vectors. Captured Culicoides specimens were subjected to RT-qPCR analysis to test for BTV. The North American vector for BTV (Culicoides sonorensis) was collected at multiple localities, constituting the first record of this species in Ontario. Identity of C. sonorensis specimens was verified using molecular analysis of three gene regions: CO1, ITS1, and EF1α. Gene sequences for Culicoides variipennis, a species easily confused with C. sonorensis, were also analyzed. Analysis revealed that EF1α introns differed between the species and may be useful as molecular identifiers. Sequences for all three gene regions were submitted to the National Center for Biotechnology Information gene database. The Brock University Rothamsted Trap operated during the summer seasons of 2013 to 2017, collecting insects at ~12m above ground on a daily basis. Collected biting midges were identified to genus, and genus tallies were compared with five climate variables using redundancy analysis (RDA) to determine factors that affect the activity of collected genera. Phenological patterns of Bezzia, Culicoides, and Probezzia were compared in detail to temperature values. A literature search was performed to evaluate progression of BTV and epizootic hemorrhagic disease virus (EHDV) across North America since their initial detections in the 1950s. Records detailing virus outbreaks were analyzed and maps displaying the chronological progression of BTV and EHDV were created, providing a visual representation of their dispersal patterns. Finally, a dichotomous key to the Nearctic biting midge genera was constructed and illustrated with high-definition photography to show key characters. This key aids with taxonomic identification of the 35 recognized genera occurring north of Mexico.
    • A study of lipid recognition and membrane binding by the human oxysterol-binding protein (OSBP).

      Mukherjee, Parthajit; Centre for Biotechnology
      Recent studies have established oxysterol-binding protein (OSBP) and members of the OSBP-related protein (ORP) family as global cellular sterol sensors that participate in non-vesicular anterograde transport of monomeric sterols from the endoplasmic reticulum to other organelles such as the Golgi and the plasma membrane. By exchanging sterols for phosphoinositides, these multi-domain proteins change the bilayer composition at membrane contact sites and thus, regulate various signaling pathways. Despite the wealth of knowledge garnered from the study of fluorescent/radiolabeled ligand-protein interactions and inter-vesicular lipid transfer assays in vitro, the precise nature of the association of ORPs with organellar membranes and the factors modulating such interactions have remained largely enigmatic. The goal of my project was to characterize the behaviour of human OSBP using a label-free analytical technique called dual polarization interferometry (DPI). This technique enables surface-immobilization of phospholipid vesicles to observe and analyze the behaviour of proteins towards adsorbed bilayers. From my investigation, I found that OSBP prefers binding to membranes containing anionic phospholipids, such as phosphatidylinositol-4-phosphate (PI(4)P), over membranes made up of neutral phosphatidylcholine (PC). In the presence of PI(4)P, the wild-type protein clearly demonstrated a rapid bilayer association, followed by PI(4)P extraction and a slower dissociation, in a dosage-dependent fashion. The OSBP-related domain (ORD) mutant, OSBP-HH/AA, due to its impaired ability to extract PI(4)P, failed to dissociate from the membrane while the pleckstrin homology domain (PHD) mutant, OSBP-RR/EE, could not associate with membranes at all. The presence of sterols did not alter OSBP’s affinity for PC membranes despite a two-fold increase in protein adsorption per unit area in the presence of cholesterol in the membrane, compared to 25-hydroxycholesterol. Both cholesterol and 25-hydroxycholesterol competed with 22-NBD-cholesterol for the binding site in the ORD of OSBP, with resulting EC50 values of 15.6 ± 0.7 nM for the former and 5.0 ± 0.5 nM for the latter. OSBP also transferred ORD-bound fluorescent cholesterol to acceptor vesicles, but the rate remained unaltered upon incorporation of PI(4)P in those membranes. These results provide useful insight into the preferential association of OSBP with membranes containing specific recognizable ligands, such as sterols and PI(4)P, and help build a molecular level description of the mechanism of this protein.
    • A study on the dynamics of the symbiosis between Metarhizium and plants

      Barelli, Larissa Ruth; Centre for Biotechnology
      Members of the Metarhizium genus exist as both insect pathogens and plant endophytes. Agricultural formulations of these fungi are utilized for their biocontrol of insect pests and numerous additional benefits for crop plants (i.e., nutrient transfer, pathogen antagonism, increased biomass, etc.). In order to develop improvements to these formulations, it is vital to understand how specific factors, such as the nutrient availability and microbial community of the soil, as well as production of secondary metabolites, influence the interaction of Metarhizium with target crop species. Metarhizium is capable of translocating nitrogen obtained through insect parasitism to plant hosts in exchange for carbohydrates. Using wax moth larvae (Galleria mellonella) injected with 15N-ammonium sulfate, it was demonstrated that nutrient-rich soil effectively inhibited transfer of insect-derived 15N from Metarhizium into the leaves of haricot bean, Phaseolus vulgaris. Colonization was maintained under all conditions and was not correlated with nitrogen transfer. Nitrogen application reduced initial colonization, but it recovered at later timepoints. The persistence of Metarhizium within the rhizosphere is influenced by the microbial community but, reciprocally, the structure of the community may respond to Metarhizium application. Although soil amendment with M. robertsii did not affect overall diversity of the root microbiome of P. vulgaris, Illumina sequencing demonstrated significant effects on particular bacterial and fungal taxa. The relative abundance of several plant growth promoting microorganisms (e.g. Bradyrhizobium) increased after Metarhizium application. When challenged with the specific bean root rot pathogen Fusarium solani f. sp. phaseoli, both the microbiome and M. robertsii were able to suppress disease. The production of fungal secondary metabolites such as destruxins may dictate interactions with plant hosts. During co-culture with bean or corn, destruxin production varied by species of Metarhizium and plant. Similar to previous reports, M. robertsii and M. acridum generally produced relatively high and low levels of destruxins, respectively. However, numerous destruxins were synthesized by M. acridum during co-culture with corn. Unraveling the metabolomic profile of these fungal-plant interactions may provide insight into mechanisms behind maintaining symbioses and patterns of strain compatibility, as well as aid in strain selection for agriculture and discovery of novel bioactive metabolites.

      ZAMAKHSHARI, HADEEL; Centre for Biotechnology (Brock University, 2013-04-19)
      Lung cancer is a major chronic disease responsible for the highest mortality rate, among other types of cancer, and represents 29% of all deaths in Canada. The clinical diagnosis of lung carcinoma still requires a standard diagnostic approach, as there are no symptoms in its early stage. Therefore, it is usually diagnosed at a later stage, when the survival rate is low. With the recent advancement in molecular biology and biotechnology, a molecular biomarker approach for the diagnosis of early lung cancer seems to be a potential option. In this study, we aimed to investigate and standardize a promising Lung ,Cancer Biomarker by studying the aberrant methylation of two tumour suppressor genes, namely RASSFIA and RAR-B, and the miRNA profiling of four . commonly deregulated miRNA (miR-199a-3p, miR-182, miR-lOO and miR-221). Four lung cancer cell lines were used (two SCLC and two NSCLC), with comparisons being made with normal lung cell lines. Our results, we found that none of these genes were methylated. We then evaluated TP53, and found the promoter of this gene to be methylated in the cancer cell lines, as compared to the normal cell lines, indicating gene inactivation. We carried out miRNA profiling of the cancer cell lines and reported that 80 miRNAs are deregulated in lung cancer cell lines as compared to the normal cell lines. Our study was the first of its kind to indicate that hsa-mir-4301, hsa-mir-4707-5p and hsa-mir-4497 (newly discovered miRNAs) are deregulated in lung cancer cell lines. We also investigated miR-199a-3p, mir-lOO and miR-182, and found that miR-199a -3p and mir-l00 were down-regulated in cancer lines, whereas miR-182 was up-regulated in the cancer cell lines. In the final part of the study we observed that mir-221 could be a putative biomarker to distinguish between the two types of lung cancer because it was down-regulated in SCLC, and up-regulated in the NSCLC cell lines. In conclusion, we found four miRNA molecular biomarkers that possibly could be used in the early diagnosis of the lung cancer. More studies are still required with larger numbers of samples to effectively establish these as molecular biomarkers for the diagnosis of lung cancer
    • Synthesis and Derivatization of Amaryllidaceae Constituents – Narciclasine and Pancratistatin

      Lapinskaite, Ringaile; Department of Chemistry
      This thesis describes the synthesis and derivatization of narciclasine and pancratistatin. A detailed description is given to the total formal synthesis of pancratistatin through a reductive transposition approach and the total and semi-syntheses of 2-epi-narciclasine and its discovery as a new natural product. The last part of this work focuses on the search for a divergent approach to access C-1 narciclasine and C-1-pancratistatin derivatives from natural narciclasine. Experimental and spectral data are provided for the new compounds.
    • Synthesis and Reactivity of Low Valent Main Group Element Complexes

      Chu, Terry; Department of Chemistry
      The β-diketiminate aluminum(I) complex NacNacAl (III-1) was shown to activate a range of substrates containing robust single and double bonds. Compound III-1 oxidatively adds a variety of H–X bonds (X = H, B, Al, C, Si, N, P, O) to give a series of four-coordinate aluminum hydride derivatives including the first example of an aluminum boryl hydride. In the case of Al–H addition, the reaction was shown to be in equilibrium and reversible. Furthermore, cleavage of aryl and alkyl C–F bonds, the latter a rare reaction with only a handful of examples in the literature, was observed with III-1. Robust C–O and C–S bonds were also activated by III-1 along with RS–SR and R2P–PR2 bonds. All novel aluminum complexes were characterized by spectroscopic methods and X-ray diffraction analysis for the majority of them. Activation of the C=S or P=S bonds in a thiourea or phosphine sulfide, respectively, was accomplished by III-1 to give the first examples of Lewis base-stabilized monomeric terminal aluminum sulfides. The nature of the Al=S bond was examined computationally as well as experimentally. Related reaction with a urea derivative gave an unexpected aluminum hydride while reaction of III-1 with phosphine oxides gave a putative aluminum oxide as a result of P=O bond cleavage. However, the aluminum oxo promptly deprotonates a neighbouring molecule to furnish an aluminum hydroxide as the isolated product. Reduction of the cationic germanium(II) complex IV-1 affords the formally zero valent germanium complex IV-4 stabilized by the bis(imino)pyridine platform. Compound IV-4 was fully characterized by spectroscopic methods and X-ray diffraction analysis. The molecule has a singlet ground state and DFT studies revealed partial delocalization of one of the germanium lone pairs into the ligand framework. Complex IV-4 was unreactive towards H–X bond activation, the lack of reactivity ascribed to the large singlet-triplet energy gap calculated. The same bis(imino)pyridine ligand was also used to prepare reduced zinc complexes. Monoreduction of the zinc dichloride precursor gave the formally Zn(I) compound IV-6. Further reduction of IV-6 in the presence of DMAP gave the formally zero valent zinc complex IV-9. Both compounds were fully characterized by spectroscopic methods, DFT calculations, and X-ray diffraction analysis which revealed that both zinc atoms are four-coordinate and adopt unusual square planar and see-saw geometry, respectively.
    • Synthesis and Reactivity of Low Valent Silicon and Phosphorus Compounds

      Baradzenka, Aliona; Department of Chemistry
      The research described in this thesis is focused on studying the use of phosphinoamidinato ligand NP (NP = [ArNC(Ph)NPiPr2]– (Ar = 2,6-iPr2C6H3)) to stabilize low-valent main group element compounds. Reduction of silane (NP)SiCl3 by magnesium allows for the high-yield preparation of base-stabilized disilylene [(NP)Si-]2. Although it is stable at room temperature, upon heating it rearranges via intermolecular N-P activation into an N,Si-heterocyclic silylene supported by a phosphine donor. The reactivity of [(NP)Si-]2 in the single bond activation of pinacolborane, phenylsilane and diphenylphosphine was tested. Additionally, the phosphidosilylene (NP)SiPPh2 that is formed in the last reaction was found to perform P-P coupling when reacted with diphenylphosphine. Experimental pursuits were taken to elucidate the mechanism of formation of disilylene [(NP)Si-]2, and some insights into its fluxionality in solution were obtained. Disilylene [(NP)Si-]2 was reacted with Si(II) and Ge(II) chlorides to yield the products of tetrylene insertion into the Si-Si bond, the low-valent compounds [(NP)Si-Si(Cl)2-Si(NP)], [(NP)Si(Cl)2Si-Si(NP)] and [(NP)Si(Cl)2Ge-Si(NP)]. Compound [(NP)Si-Si(Cl)2-Si(NP)] is the kinetic product of the direct insertion of SiCl2 fragment into Si-Si bond of [(NP)Si-]2. The thermodynamic product of the insertion of silicon dichloride is disilylene [(NP)Si(Cl)2Si-Si(NP)] that is the consequence of migration of chlorides to terminal Si center. The reaction of [(NP)Si-]2 with GeCl2 produced only one compound [(NP)Si(Cl)2Ge-Si(NP)] that is a rear example of germylene-silylene. Interaction of [(NP)Si-]2 with SiCl4 and SiHCl3 produced a new example of acyclic disilyl silylene. Reduction of (NP)PCl2 with potassium graphite allowed isolation of the base-stabilized phosphinidene (NP)P. Its reactivity was studied. The use of substrates with E-H bonds like pinacolborane, phenylsilane and diphenylphosphine yielded compounds (NP)Bpin (pin = (OC(CH3)2)2) and NPH, (NP)SiH2Ph and NPH, NPH-P-PPh2, respectively, which are the result of N-P and E-H bond metathesis. Upon reaction with tetrachlorobenzoquinone both phosphorus atoms of phosphinidene (NP)P underwent oxidation. (NP)P reacted with benzaldehyde and phenylisocyanate as a phospha-Wittig reagent. Additionally, (NP)P was transformed into phosphinidene oxide (NP)P=O, iminophosphine (NP)P=Np-Tol and phosphinidene sulfide (NP)P=S. Transient (NP)P=O and (NP)P=Np-Tol were captured by para-tolyl isocyanate to form compound (NP)P(N,N-(Np-Tol)2CO). All the compounds were fully characterized by NMR and for most of them single crystal X-ray structure was obtained.
    • Synthesis and Reactivity of Main Group Complexes for Applications in Small Molecule Activation

      Nguyen, Minh Tho; Department of Chemistry
      The work described in this thesis is focused on the preparation of a series of novel main group complexes, featuring unusual structural and bonding situations, and the study of their reactivity toward small molecules. The new zinc complexes dimphZnBu (V-2) and dimphZnCl2Li(THF)3 (V-3), supported by a diiminophenyl (dimph) ligand were prepared. The reaction of complex V-3 with LiHBEt3 resulted in hydride transfer to the C=N imine group to give an unusual zinc dimer (V-7). The latter transformation occurs via formation of compound (ɳ1(C),ĸ1(N)- 2,6-(2,6-iPr2C6H3N=CH)2C6H3)2Zn (V-5) which can be also accessed by reduction of V-7 with KC8. Diiminophenyl (dimph) proved to be an excellent ligand platform to stabilise a low-valent phosphorus centre. The resultant compound dimphP (VI-2), which can be rationalised as an imino-stabilised phosphinidene or benzoazaphopshole, shows remarkable chemical stability toward water and oxygen. VI-2 reacts with excess strong acid HCl to generate the P(III) chloride (dimHph)PCl (VI-6). Surprisingly, substitution of the chloride under some nucleophilic (KOBut) and electrophilic conditions (Me3SiOTf) regenerates the parent compound VI-2 by proton removal from the weakly acidic CH2N position. A related species (dimH2ph)P (VI-10) is produced upon thermal rearrangement of the hydride (dimHph)PH (VI-9). The molecular structure and reactivity of compounds VI-2 and other related compounds are also discussed. The reduction of the O,C,O-chelated phosphorus (III) chloride (VI-16) ( O,C,O = 2,6-bis[(2,6-diisopropyl)phenoxyl]phenyl) with KC8 or PMe3 resulted in the formation of a cyclic three-membered phosphorus compound (VI-18). The intermediacy of phosphinidene VI-17 was confirmed by trapping experiments and a VT 31P{1H} NMR study. The reaction of in-situ generated phosphinidene with either PhSiH3 or HBpin resulted in the formation of an unprecedented phosphine (VI-23). The treatment of VI-16 with two equivalents of DippNHC carbene led to ArP(Cl)NHC product (VI-24). The germylone dimNHCGe (dimNHC = diimino N-Heterocyclic Carbene, VII-8) was successfully prepared by the reduction of germanium cation (VII-7) with KC8. The molecular structure of VII-8 was unambiguously established, using NMR spectroscopy and single-crystal X-ray diffraction analysis. The reactivity of VII-8 was investigated. VII-8 is inactive towards butadiene but undergoes an oxidative cyclization with tetrachloro-o-benzoquinone to give a tetragermanium derivative. VII-8 undergoes oxidation addition of CH3I and PhI, followed by an unusual migration of the Me and Ph groups from germanium to the carbene ligand. Related chemistry takes place upon protonation with dry HCl, which results in the migration of the hydride to the carbene ligand.
    • Synthesis of Cyclopropenium-Appended Organocatalysts and Applications

      Smajlagic, Ivor; Department of Chemistry
      Enclosed within this dissertation is the development and application of multiple cyclopropenium-containing compounds formally belonging to two closely-related classes of organocatalysts, namely thioureas and squaramides. The former catalyst, coined as a thiourea-cyclopropenium, is deployed in pyranylation reactions of alcohols and phenols, as well as Friedel–Crafts alkylation, while the latter—a squaramide-cyclopropenium catalyst—targets oxime ether bond formation. Accompanying these innovative synthetic methodologies are comprehensive experimental and computational mechanistic studies that work in synergy to delineate numerous key features, all of which provide valuable information with respect to understanding the multifaceted nature of catalysis. Experimental and spectral data are provided for all new compounds.
    • Synthesis of unnatural analogues of pancratistatin and narciclasine

      Vshyvenko, Sergey; Department of Chemistry (Brock University, 2014-05-07)
      Described herein is the chemoenzymatic synthesis of several different types of unnatural analogues of Amaryllidaceae constituents. Development and refinement of existing and design and execution of new approaches towards the synthesis of C-1 analogues of pancratistatin and A-ring heterocyclic analogues of narciclasine are discussed. Evaluation of the new analogues as cancer growth inhibitory agents is also described
    • TA tales : [re]storying the teaching and learning experiences of university teaching assistants

      Grose, Jill D.; Department of Graduate and Undergraduate Studies in Education (Brock University, 2012-04-04)
      This inquiry examines reported critical incidents that shaped the lived experience of 5 university TAs as they negotiated multiple roles and relationships within the teaching and learning context. Questions and ensuing conversations explore the ways in which these critical incidents in teaching contributed to the TAs' understanding of themselves as teachers, of teaching and learning tensions in higher education, and of the institutional contexts in which they work. The inquiry also explores the ways in which narrative, particularly creative fiction, can represent the stories TAs tell of their experiences.
    • Talking during class, packing up books and name calling: Is it really that big a deal? An exploration of classroom incivility

      Spadafora, Natalie; Department of Child and Youth Studies
      The main goal of my dissertation was to explore and expand our understanding of the concept of adolescent classroom incivility. Specifically, I wanted to expand the current research on classroom incivility in children and youth using a range of methods. Methods comprised validating a measure of engagement in uncivil behavior, including open-ended responses to understand the experiences and viewpoints of both adolescent students and their teachers and exploring social network position in relation to engaging in classroom incivility. In Study 1, I validated a scale of uncivil behavior in the classroom. This validation confirmed subscales of intentional and unintentional classroom incivility in adolescents. This study also assessed construct validity via the examination of associations between classroom incivility with self- and peer-reported behavior and mental health correlates. As well, I investigated differential personality profiles of adolescents who reported engaging in intentional vs. unintentional uncivil behavior. Study 2 focused on comparing and contrasting the perceptions and experiences of classroom incivility of middle and high school teachers and students. This study used both quantitative reporting and qualitative methods to investigate how middle and high school teachers were experiencing and understanding classroom incivility compared to students. The results of this study indicated that there were differences in how uncivil behaviors were being perceived by students and teachers, depending on the classroom or individual circumstances. Finally, Study 3 was an exploratory study that investigated the association between social network position and self-reported engagement in classroom incivility. Results indicated a curvilinear association between social network position and classroom incivility, such that students who engaged in the highest or lowest levels of classroom incivility had lower social network position, while students who engaged in moderate levels of classroom incivility had the highest levels of social network position. Taken together, these studies have expanded our knowledge and understanding of adolescent classroom incivility. These results can inform intervention of uncivil behavior in the classroom and have highlighted the importance of limiting uncivil behavior in adolescence in an effort to promote a civil society.
    • Tea types and their effects on in vitro mineralization and in vivo bone structure and density

      McAlpine, Michael D.; Applied Health Sciences Program
      The consumption of tea has many proposed health benefits thought to likely be the result of an abundance of unique polyphenols. In particular, one exciting potential health benefit of tea is its capacity to have bone supportive effects when consumed throughout life. Prior to testing the potential bone supportive effects, it was important to characterize several types of tea and determine the ideal steeping time for each tea, maximizing the quantity of polyphenols while also maintaining taste (Study 1). Results from this study were congruent with manufacturer’s recommendations. Following this, several types of teas and tisanes were tested in an in vitro osteoblast model to determine if there were any alterations in quantity of mineral produced (Study 2). Findings demonstrated that all teas effectively increased mineralization at a dietary concentration of polyphenols, but red rooibos tea appeared to produce the greatest effects. The next important aspect which needed to be clarified was if there was an optimal concentration of red rooibos tea that elicited maximal results (Study 3). To determine this, a dose response study was conducted in the same osteoblast model as study 2 and mineral quantity was measured. From this study a positive dose-dependent response was observed without any signs of toxicity, suggesting that high concentrations may be beneficial. Following the initial in vitro studies it was important to test red rooibos tea in a physiologically relevant model of elevated bone turnover, pregnancy and lactation (Study 4). Female Sprague-Dawley rats were randomized to one of the following groups: PREG TEA (pregnant and received a supplemental level of red rooibos: ~2.6 g /kg body weight/day in water), PREG WATER (became pregnant and received water), or NONPREG CON (age-matched, non-pregnant control) from 2 weeks prior to pregnancy (age 8 weeks) through to 4 months post-lactation. Results demonstrated that there were immediate losses of both trabecular and cortical bone following lactation. However, cortical bone rapidly recovered in both pregnancy groups while the majority of trabecular outcomes only partially recovered and appeared to have permanent reductions. When comparing the two pregnancy groups, there were no differences in cortical bone post-lactation but there were significant improvements in several of the trabecular outcomes in rats that received red rooibos herbal tea. The findings from this thesis demonstrated in progressively more complex and physiologically relevant models that tea does have the capacity to be bone supportive, particularly during periods of high turnover.
    • Teachers Without Borders: Exploring Experiences, Transitions, and Identities of Refugee Women Teachers from Yugoslavia

      Ratkovic, Snezana; Department of Graduate and Undergraduate Studies in Education (Brock University, 2014-03-20)
      Prior to September 11 2011, Canada was recognized as a leading advocate of international refugee protection and the third largest settlement country in the world. University educated refugees were admitted to the country in part on the basis of their education, but once in Canada their credentials were often ignored. The purpose of this study was to explore, through a transnational feminist lens, immigrant and settlement experiences of refugee female teachers from Yugoslavia who immigrated to Canada during and after the Yugoslav wars; to document the ways in which socially constructed categories such as gender, race, and refugee status have influenced their post-exile experiences and identities; and to identify the government's role in creating conditions where the women were either able or unable to continue in their profession. In this study, I employed both a transnational feminist methodology and narrative inquiry. The analysis process included an emphasis on the storying stories model, poetic transcription, and concentric storying. The women’s voices are represented in various forms throughout the document including individual and collective narratives. Each narrative contributed to a detailed picture of immigration and settlement processes as women spoke of continuing their education, knowing or learning the official language, and contributing to Canadian society and the economy. The findings challenge the image of a victimized and submissive refugee woman, and bring to the centre of discourse the image of the refugee woman as a skilled professional who often remains un- or underemployed in her new country. The dissertation makes an important contribution to an underdeveloped area in the research literature, and has the potential to inform immigration, settlement, and teacher education policies and practices in Canada and elsewhere.