This thesis deals primarily with supramolecular chemistry based on cucurbit[n]uril (CB[n], n = 7 and 8) host molecules. The research has been focused on the synthesis and characterization of host-guest complexes CB[n] with aromatic guest molecules, and the study of the effects of the host-guest complexation on the chemical reactivity and spectroscopic properties of the included guests, such as their photoreactivity and their UV-visible absorption and emission properties, in aqueous solution. The [4+4] photodimerization of protonated 2-aminopyridine (APH+) occurs stereoselectively to give the anti-trans product as the result of a preferred orientation of two APH+ guests in the cavity of CB[7]. The CB[7] host inhibits photohydration in the course of the photoisomerizations of protonated trans-1,2-bis(4-pyridyl)ethylene and trans-1,2-bis(1-methyl-4-pyridinium)ethylene by including the (4-pyridyl)ethylene portion of the guest, while this is not observed with trans-1,2-bis(1-hexyl-4-pyridinium)ethylene, as preferential inclusion of the hexyl groups leaves the vinyl group vulnerable to photohydration. Very strong CB[7] complexation of (E)-1-ferrocenyl-2-(1-methyl-4-pyridinium)ethylene completely inhibits the (E)→(Z) photoisomerization process. The H/D exchange rates and acidities of the C(2)-proton of cationic imidazolium and thiazolium (including thiamine and thiamine phosphates) carbon acids are decreased upon their complexation with CB[7]. Inclusion of protonated aromatic amines (and aromatic alcohols) in the cavity CB[7] significantly decreases their ground and excited state acidities, such that the emission is switched from the neutral amine to the protonated amine excited state, resulting in changes in the color of fluorescence. The fluorescence of acridizinium cations can be switched off by the formation of 2:1 complexes with CB[8] and then switched back on again by the addition of CB[7] or a competing guest molecule. The stabilization of the deep blue color of the 4,4’-bis(dimethylamino)diphenyl carbonium ion, upon complexation of the corresponding carbinol with CB[7], results from a complexation-induced shift in the carbinol/carbonium ion equilibrium. A dramatic purple to blue color change in pinacyanol chloride upon addition of CB[7] is due to a partial breakup of dye aggregates, upon the interactions of the dye with the host molecule. The CB[n] complexation-induced emission and/or absorption color switch have the potential to be employed in molecular switches and in chemical sensing. / Thesis (Ph.D, Chemistry) -- Queen's University, 2007-08-07 09:21:06.553

N-glycosylation is a metabolic process found in all three domains of life. It is the attachment of a polysaccharide glycan to asparagine (Asn) residues within the amino acid motif, Asn-Xaa-Ser/Thr. In the archaeon, Methanococcus maripaludis, a tetrasaccharide glycan was isolated from purified flagella and its structure determined by mass spectrometry analysis. The linking sugar to the protein is surprisingly, N-acetylgalactosamine (β-GalNAc), with the next proximal sugar a derivative of N-acetylglucosamine (β-GlcNAc), being named β-GlcNAc3Ac, and the third sugar a derivative of N-acetylmannosamine (β-ManNAc), with an attached threonine residue on the C6 carbon (β-ManNAc3NAm). The terminal sugar is an unusual diglycoside of aldulose ((5S)-2-acetamido-2,4-dideoxy-5-O-methyl-α-L-erythro-hexos-5-ulo-1,5-pyranose). Previous genetic analyses identified the glycosyltransferases (GTs) responsible for the transfer of the second and third sugars of the glycan, as well as the oligosaccharyltransferase (OST) which attaches the glycan to protein. Left unidentified were the first and fourth GTs, the flippase as well as any genes involved in glycan sugar biosynthesis and modification. In this work, genes suspected to be involved in the biosynthesis of N-linked sugars, as well as those that might encode the missing GTs and flippase were targeted for in-frame deletion. Mutants with a deleted annotated GT gene (MMP1088) had a small decrease in flagellin molecular weight as determined by immunoblotting. Mass spectrometry (MS) analysis confirmed that the N-linked glycan was missing the terminal sugar as well as the threonine found on the third sugar of wildtype cells. Mutants with a deleted gene annotated to be involved in acetamidino synthesis (a functional group that is present on the third sugar), also had a decrease in flagellin molecular weight. MS analysis determined that the N-linked glycan was missing the acetamidino group on the third sugar as well as its attached threonine, along with the terminal sugar. Both mutants were able to assemble functional flagella but had impaired motility compared to wildtype cells in mini-swarm agar. Deletions were also constructed in four other GT genes considered candidates in assembly of the linking sugar. However, none of these mutants had the expected decrease in flagellin molecular weight. With the work done in this study, the glycosyl transferase that attaches the last sugar of the M. maripaludis N-linked assembly pathway has been identified as well as a gene involved in the biosynthesis and modification of the glycan sugars. / Thesis (Master, Microbiology & Immunology) -- Queen's University, 2009-07-07 15:45:19.052

Cosmological simulations show that dark matter halos contain a wealth of substructure. These subhalos are assumed have a mass distribution that extends down to the smallest mass in the Cold Dark Matter (CDM) hierarchy, which lies below the current resolution limit of simulations. Substructure has important ramifications for indirect dark matter detection experiments as the signal depends sensitively on the small-scale density distribution of dark matter in the Galactic halo. A clumpy halo produces a stronger signal than halos where the density is a smooth function of radius. However, the small-scale Universe presents a daunting challenge for models of structure formation. In the CDM paradigm, structures form in a hierarchical fashion, with small-scale perturbations collapsing first to form halos that then grow via mergers. However, near the bottom of the hierarchy, dark matter structures form nearly simultaneously across a wide range of scales. To explore these small scales, I use a series of simulations of scale-free cosmological models, where the initial density power spectrum is a power-law. I can effectively examine various scales in the Universe by using the index in these artificial cosmologies as a proxy for scale. This approach is not new, but my simulations are larger than previous such simulations by a factor of 3 or more. My results call into question the often made assumption that the subhalo population is scale-free. The subhalo population does depend on the mass of the host. By combining my study with others, I construct a phenomenological model for the subhalo mass function. This model shows that the full subhalo hierarchy does not greatly boost the dark matter annihilation flux of a host halo. Thus, the enhancement of the Galactic halo signature due to substructure can not alone account the observed flux of cosmic rays produced by annihilating dark matter. Finally, I examine the nonlinear power spectrum, which is used to determine cosmological parameters based on large-scale, observational surveys. I find that in this nonlinear regime, my results are not consistent with currently used fitting formulae and present my own empirical formula. / Thesis (Ph.D, Physics, Engineering Physics and Astronomy) -- Queen's University, 2009-09-25 01:01:39.714

The archaeal flagellum is a rotating prokaryotic motility apparatus used for swimming motility and adhesion; however, it is more closely related to the bacterial type IV pilus system than its bacterial namesake. Methanococcus maripaludis is a highly flagellated, obligately anaerobic methanogen and is used as the archaeal model system during this study. The identified structural genes of the archaeal flagella are transcribed by a single fla operon; however, the interactions between the majority of the Fla proteins has yet to be elucidated. In this work, several techniques were attempted to determine the protein-protein interactions between Fla proteins, including membrane fractionation experiments and in vitro dimerization assays. Evidence from these experiments suggests that two proteins, FlaC and FlaE, have the ability to self-associate. The M. maripaludis flagella system is also used as a model for the study of the N-linked glycosylation pathway in the domain, due to the presence of a tetrasaccharide N-linked to flagellin monomers. Previous work has identified several of the processes involved in the assembly of this glycan, including glycosyltransferases, the oligosaccharide transferase and several of the key components involved in the biosynthesis of the sugar residue precursors. However, many of the enzymes responsible for biochemical modifications to the sugar residues remain to be determined. The operon structure of the genes between mmp1080 and mmp1095 was experimentally confirmed using RT-PCR, and each of the operons contains at least one gene involved in the biosynthesis of the N-linked glycan. In-frame deletions of genes in this region were characterized for effects on the N-linked glycan. Evidence suggests that Mmp1082 and Mmp1083 are acting in conjunction with Mmp1081 in the addition of an acetamidino functional group to the third sugar residue. Mmp1085 was determined to be a methyltransferase responsiblefor the methylation of the terminal sugar residue. Additionally, Mmp1087 and Mmp1094 were identified as potentially having an effect on the glycan. Though this work, the breadth of knowledge in regards to both the archaeal flagella and the N-linked glycosylation process in the domain has been increased. / Thesis (Master, Microbiology & Immunology) -- Queen's University, 2011-01-28 11:50:05.542

The objective of this thesis is to prepare new photochromic N,C-chelate four-coordinate organoboron compounds and investigate their photophysical and photochemical properties. Phenylpyridine-based organoboron compound (PhPyBMes2) was prepared and studied with NMR, X-ray, and UV-Vis. Experimental and theoretical results established that PhPyBMes2 is photochromic and the photoisomerization process involves a reversible intramolecular C-C bond formation/breaking. The structure of the dark colored isomer of PhPyBMes2 was established by 2D NMR experiments and computational studies. The discovery of the photochromic behavior of PhPyBMes2 led to the investigation of other phenylpyridine-based organoboron compounds. A series of substituted PhPyBMes2 compounds were synthesized with substituents on the phenyl ring or the pyridine ring of the N,C-chelate. Two other compounds were synthesized by substituting the mesityl rings in PhPyBMes2 with phenyl or pentaflurophenyl rings. The photophysical and photochemical properties of these compounds were studied by NMR, UV-Vis, and DFT/TD-DFT. The studies established that the steric hindrance imposed by the mesityl groups and the nature of substituents on the N,C-chelate have substantial effects on the photoisomerization process. New organoboron compounds based on N,C-chelates other than phenylpyridine were prepared and their photochemical and photophysical properties studied using NMR, UV-Vis, and DFT/TD-DFT. The phenyl group in the N,C-chelate was replaced by TMS-furan, TMS-thiophene, benzofuran, benzothiophene, and N-phenyl pyridylindole groups. The conducted studies show that these new compounds have photochromic properties similar to those of phenylpyridine-based compounds. Crystals of the dark isomer of the N-phenyl pyridylindole organoboron compound were successfully grown and the structure of the dark isomer was determined by X-ray diffraction. New organoboron compounds based on phenyl-benzoxazole and phenyl-benzothiazole have been also prepared and studied. The photoisomerization of these compounds is similar to the other N,C-chelate organoboron compounds but their thermal behavior is different. / Thesis (Ph.D, Chemistry) -- Queen's University, 2011-08-22 11:50:50.811

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Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Sialic acids are prevalent in many organisms and facilitate a range of cellular processes in both bacteria and mammals. Whilst a variety of sialic acids are present in nature, N-Acetylneuraminic acid (NANA) is the most common and plays a key role in the pathogenesis of a select number of neuroinvasive bacteria such as Neisseria meningitidis. These pathogens coat themselves with polysialic acids, mimicking the exterior surface of mammalian cells and consequentially concealing the bacteria from the host’s immune system. NANA is synthesised in prokaryotes via a condensation reaction between phosphoenolpyruvate and N-acetylmannosamine. This reaction is catalysed by the domain swapped, homodimeric enzyme, N-acetylneuraminic acid synthase (NANAS). Each NANAS monomer is comprised of two distinct domains; a catalytic domain linked to an antifreeze protein-like (AFPL) domain. This thesis outlines research into the role of the AFPL domain using a range of structural and kinetic analyses to compare variant enzymes to the natural, NmeNANAS enzyme. An investigation was also made into the evolutionary relationships between NANAS and other bacterial sialic acid synthases such as Legionaminic acid synthase and Pseudaminic acid synthase.