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No description available.

M.S.

Thesis advisor: Christina Faherty / Shigella, a Gram-negative bacterial pathogen, induces inflammation and diarrhea by invading the colonic epithelium. Annually, millions of Shigella infections occur globally, mainly in malnourished children. Despite extensive research, no effective vaccine exists. This work explores the mechanisms of Shigella proliferation before colonic infection, where an adverse environment is encountered, including bile salts exposure. One means of bile salts evasion is possibly lipopolysaccharide (LPS) modification. LPS—O-antigen, the polysaccharide core, and the lipid A—is a crucial outer membrane component for virulence. Transposon mutant analysis suggested a role of LPS in bile salts resistance; thus, the goal of this study was to define Shigella LPS modifications following bile salts exposure. LPS mutants were investigated to distinguish crucial components of the LPS structure for bile salts resistance. Mutants were analyzed relative to wild type for growth in bile salts and biofilm formation. The LPS from all strains was purified and analyzed by polyacrylamide gel electrophoresis. Stained gels show modifications in the Oag, lipid A, and core components. Key bands were sent for mass spectrophotometry sequencing. Results indicate that the O-antigen regulates Shigella bile salts resistance, as the complete O-antigen deletion mutant and partial deletion mutants exhibited slow growth in bile salts and failed to form a biofilm in the presence of bile salts. This work highlights the importance of bile salts exposure for Shigella in future targeted antibodies against the pathogen. / Thesis (BS) — Boston College, 2019. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Departmental Honors. / Discipline: Biology.

Ionic liquid forming compounds often display low melting points (a lack of crystallisation at ambient temperature and pressure) due to decreased lattice energies in the crystalline state. The degree of anion-cation contact with respect to the type, strength and number of interactions is a major factor determining the lattice energies, melting point and general behaviour of ionic liquid forming salts. Intermolecular interactions between the anion and cation and the conformational states of each component of the salt are of interest since distinctive properties ascribed to ionic liquids are determined to a significant extent by these interactions. The direct insight into the spatial relationship between cation and anion provided by the analysis of crystal structures provides a basis from which features of the ionic liquid can be generally understood, since the short range order and interactions of related, non-crystalline compounds may be similar to those of the crystalline form. However, it is difficult to predict whether a particular ionic pair will produce a liquid at room temperature, due to numerous possible combinations of cations and anions and the subtleties of their interactions. Crystal engineering is the ability to assemble molecular or ionic components into the desired crystalline architecture by engineering a target network of supramolecular interactions known as synthons. In this investigation the problem of ionic liquid design is addressed using the concepts of crystal engineering in an inverse sense, the so-called anti crystal-engineering approach. A topical area in which the anti crystal-engineering concept may be of some value is that of Ionic Liquid Phases of Pharmaceutically Active Ions (Active Ionic Liquids). Thus, by using the knowledge gained of the intermolecular interactions, packing and ionic conformation which occur within ‘traditional’ ionic liquids, combined with the knowledge of which functional group combinations yield supramolecular synthons resulting in crystalline subjects, and the subsequent prevention thereof (anti crystal-engineering), appropriate ions shall be selected which may result in ionic liquid formation. The intermolecular interactions of a series of: • crystallised bis(trifluoromethanesulfonyl)amide (NTf2) and bis(methanesulfonyl)amide (NMes2) ionic liquids, • low melting N-alkyl-2-methyl-3-benzylimidazolium iodide salts with a range of alkyl chain lengths, from n=1 to 6 and including both n-butyl and s-butyl chains, • 1-methyl-1-propylpyrrolidinium chloride and, • a number of low melting salts containing trihalide and monohalide ions, in combination with typical IL organic cations namely, 1-ethyl-3-methylimidazolium, 1-ethyl-1-methylpyrrolidinium and 1-propyl-1-methylpyrrolidinium, were qualitatively investigated and/or compared using a combination of crystallographic, Hirshfeld surface and thermal analysis techniques. The NMes2 salts are known to exhibit higher glass transitions and higher viscosities than those of the NTf2 salts. The origins of these differences were analysed in terms of the importance of factors such as the C-H•••O hydrogen bond, fluorination, presence of an aromatic moiety and length of alkyl chain, using the Hirshfeld surfaces and their associated fingerprint plots. Additionally, the existence of C-F•••π and C-H•••π interactions were elucidated and the significance of anion-anion interactions was recognised. Thermal analysis of the N-alkyl-2-methyl-3-benzylimidazolium iodide salts revealed that the methyl- and (s-)butyl substituted salts have a significantly higher melting point than the rest of the series. Analysis of these crystal structures allowed examination of the influence of the substitutions on the different cation-anion and cation-cation interactions and thus the physical properties of the salts. Thermal analysis of the monohalide and trihalide salts revealed that the tribromide salts are lower melting than their monohalide analogues. Analysis of these crystal structures revealed the influence of the anions and the crystal packing on the physical properties of the salts. A series of crystalline and liquid salts were prepared from cations and anions drawn from Active Pharmaceutical Ingredients (APIs) and Generally Recognized As Safe (GRAS) materials. The solid-state structures of the crystalline salts were used as a basis for the anti-crystal engineering approach in the preparation of several “Active Ionic Liquids” (AILs). However, a side product also resulted during the synthetic route namely, methyl 9H-xanthene-9-carboxylate, a side product resulting from the API, propantheline. The results and methodology of the anti-crystal engineering procedure and the subsequent successful preparation and characterization of pharmaceutical ionic compounds are reported herein.

In response to growing levels of resistance to currently used antimalarials, there is an urgent need to develop drugs that exhibit novel mechanisms to kill Plasmodium parasites. The objective of this study was to examine the antiparasitic activity of newly synthesized compounds based on imidazolium and triazolium rings. According to our structure/activity relationship studies the key components appear to be their positively charged rings and hydrophobic side groups, and bivalent compounds, which incorporate two positively charged rings, show even greater potency than monovalent compounds. Depending on the concentration used, our compounds appear to primarily inhibit intracellular parasite development or invasion into red blood cells. Selected compounds have been tested in vivo using a P. berghei ANKA murine model. Together, our findings demonstrate that small imidazolium- and triazolium-based compounds display both in vitro and in vivo activity through a novel mechanism of action that may involve inhibition of erythrocyte invasion.

In response to growing levels of resistance to currently used antimalarials, there is an urgent need to develop drugs that exhibit novel mechanisms to kill Plasmodium parasites. The objective of this study was to examine the antiparasitic activity of newly synthesized compounds based on imidazolium and triazolium rings. According to our structure/activity relationship studies the key components appear to be their positively charged rings and hydrophobic side groups, and bivalent compounds, which incorporate two positively charged rings, show even greater potency than monovalent compounds. Depending on the concentration used, our compounds appear to primarily inhibit intracellular parasite development or invasion into red blood cells. Selected compounds have been tested in vivo using a P. berghei ANKA murine model. Together, our findings demonstrate that small imidazolium- and triazolium-based compounds display both in vitro and in vivo activity through a novel mechanism of action that may involve inhibition of erythrocyte invasion.

The purpose of the study was to determine the effect of four salt concentrations and four acid levels of soil solution on the germination of Quercus emoryi and Robinia neo-mexicana seeds, and to study the effects of the cation concentration changes in solution (Na, Ca, Mg, K) and exchangeable cation concentration. The solution extracts and exchange phases of both soils, salt accumulation in the soil increased by increasing the salinity and acidity of the water applied. Exchangeable sodium was related directly to the SAR of the applied solutions. The soil responded differently to the salty water and acid water. Both soil treatments released Ca, Mg and K to the soil solution from the dissolution of the primary minerals and cation exchange reaction.

The effects of high sodium chloride (NaCl) levels on Na and nutrient retention of three soil substrates and on littleleaf linden growth in different soil substrates were studied in the laboratory and the greenhouse, within the framework of a substrate selection program for trees planted in downtown Montreal. In addition, the effects of the structural soil (SS) compaction were studied in the first greenhouse experiment. The first greenhouse experiment was established in a factorial arrangement of four soils x four salt levels in a completely randomized design with five replicates. The four soil types were (1) L with a bulk density (BD) of 1.53 g/cm3, (2) LP with a BD of 1.26 g/cm3, (3) SS with a BD of 1.8 g/cm 3 (SS1.8), and (4) SS with a BD of 2.0 g/cm3 (SS2.0). The second greenhouse experiment had a split plot design. Two fertilization levels (with fertilizer and without fertilizer) were randomly arranged as the main plots on ten benches. Within each main plot, the combinations of three NaCl levels (0, 0.5 and 1.0 g NaCl/kg soil) and three soil substrates (L with a BD of 1.40 g/cm3, LP with a BD of 1.13 g/cm 3 and SS2.0) were randomized in the sub-plots. Results from the laboratory leaching experiment indicated that SS had the fastest Na leaching rate and highest Na loss, while LP retained more Na than SS or L. (Abstract shortened by UMI.)

Methodologies for expanding the architectural diversity of -N-heterocyclic carbene (NHC) pincer ligand precursors and transition metal complexes have been developed for the production of more efficient catalyst, which will be employed in the synthesis of pharmaceuticals. An efficient route for the synthesis and isolation of bis-1,3-(3'-aryl-N-heterocycl-1'-yl)arenes has been established, and preliminary data for metalation and transmetalation of a N, N'-diaryl imidazolium salt has been acquired. Additionally, a proficient methodology for the synthesis of mixed, unsymmetrical -NHC pincer ligand precursors has been discovered, and preliminary data for mixed, unsymmetrical transition metal complexes is also included. These methodological expansions will lead to more efficient catalyst that decrease the expenditure of energy required for the synthesis of pharmaceuticals, thus making their synthesis more favorable for the environment and their price more affordable for consumers.