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.

Gold(I) and copper(I) imidazolium complexes were synthesized and probed for use as bulky Lewis acids in frustrated Lewis pairs (FLPs) with bulky phosphines and amines. Their reactivity with small molecules was investigated and the compounds were fully characterized by multinuclear NMR spectroscopy, elemental analysis and X-ray crystallography. Secondly, a new methylene-linked boron-sulfur Lewis acid was synthesized. Its thermodynamic properties were determined and its reactivity with terminal and internal alkynes was demonstrated. Adducts and heterocycles of this boron-sulfur system were fully characterized by multinuclear NMR spectroscopy, elemental analysis and X-ray crystallography. The application of these new systems for the activation of small molecules is described in this thesis.

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.

Gold(I) and copper(I) imidazolium complexes were synthesized and probed for use as bulky Lewis acids in frustrated Lewis pairs (FLPs) with bulky phosphines and amines. Their reactivity with small molecules was investigated and the compounds were fully characterized by multinuclear NMR spectroscopy, elemental analysis and X-ray crystallography. Secondly, a new methylene-linked boron-sulfur Lewis acid was synthesized. Its thermodynamic properties were determined and its reactivity with terminal and internal alkynes was demonstrated. Adducts and heterocycles of this boron-sulfur system were fully characterized by multinuclear NMR spectroscopy, elemental analysis and X-ray crystallography. The application of these new systems for the activation of small molecules is described in this thesis.

Les avancées dans la recherche de complexes doués de grandes activités catalytiques ont conduit à l'utilisation intensive des carbènes N-hétérocycliques (NHCs). Depuis une quinzaine d'années cette classe de ligands a fait ses preuves en donnant accès à des complexes d'une grande<br />stabilité et très actif en comparaison à d'autres ligands.<br />Les récents travaux sur la synthèse de ligands bidentes comportant un NHC et un groupement azoté coordonnant, puis de complexes de palladium, rhodium et iridium très actifs en catalyse, nous ont orientés vers la préparation de ligands analogues avec des hétéroatomes différents.<br /><br />Dans cette thématique nouvellement développée au sein de notre équipe, nous avons mis au point deux méthodes de synthèse originales donnant accès à de nouveaux précurseurs de carbènes N-hétérocycliques, composés d'un groupement imidazolium et d'un second groupement<br />coordonnant qui sera soit une phosphine, soit un thioéther.<br /><br />L'étude de ces ligands a permis de développer une chimie de coordination riche avec Ni, Pd, Rh, Ru et Ir. Ainsi, quatre modes de coordination ont été mis en évidence : soit une monocoordination de l'hétéroatome ou du NHC, soit une double coordination de l'hétéroatome et du carbène Nhétérocylique selon des modes dit « normal » ou « anormal ». Nos études ont montré que le mode de coordination adopté par les ligands dépendait des conditions expérimentales, de la réactivité du métal et de son affinité pour l'hétéroatome. <br /><br />L'obtention de tels complexes a permis d'effectuer quelques tests préliminaires en hydrosilylation et hydrogénation avec le rhodium(I). Une étude approfondie de la réaction de couplage d'un organomagnésien et d'un halogénure d'aryle (réaction de Kumada-Corriu-Tamao) a été menée avec les complexes du nickel(II).

The synthesis method for PEG/alkyl-based imidazolium/pyridinium ionic liquids was studied. Four steps were used to fabricate the membranes: polymerization, chloromethylation, linkage of the polymers with the pendent groups and membrane cast. Permeabilities and CO2/N2 selectivity of two membranes were examined and each showed remarkable CO2/N2 selectivity. CO2 permeability of the [PSM-MIM][Cl] membrane is better than that of the [PSM-MEIM][Cl] membrane, which is due to the steric hindrance of the methoxyethyl group. The syntheses of PEG/alkyl-based imidazolium/pyridinium ionic liquids (IL) were studied. PEG-based ILs were demonstrated to have better H2S solubilities than the alkyl-based ILs. H2S solubilities of the imidazolium ILs and pyridinium ILs were compared. The anion effects on H2S solubilities have been investigated, while the temperature effects on H2S solubilities will need to be studied in the near future.

La récupération et le recyclage des systèmes catalytiques dans la formation de liaisons carbone-carbone reste un défi scientifique important pour des raisons économiques et environnementales. Leur immobilisation sur des polymères insolubles permet une séparation simple par filtration et une purification facile des composés finaux. Les organosilices sont des gels de silice modifiés par des fragments organiques. Elles ont été appliquées comme supports pour une grande variété de catalyseurs. Dans ce travail, différentes organosilices ont été préparées par le procédé sol-gel ou par des méthodes de post-fonctionnalisation. Les matériaux contenant des alkylidènes de ruthénium ont été testés pour des réactions de métathèse d'oléfines, tandis que ceux qui sont dérivés de prolinamides sont des organocatalyseurs chiraux efficaces pour les aldolisations asymétriques (recyclage possible jusqu'à 5 fois). Enfin, on a contrôlé les propriétés morphologiques et texturales des silsesquioxanes pontées en ajustant les conditions de synthèse lors de l'hydrolyse-polycondensation de sels d'imidazolium silylés contenant des fonctions urée. / The recovery and recycling of catalytic systems in carbon – carbon bond forming reactions remains a scientific challenge of economical and environmental relevance. Their immobilization onto insoluble polymers allows a simple separation of the final compounds by filtration and an easy purification. Organosilicas are silica gels modified with organic moieties, which have been applied as versatile supports for a great variety of catalysts. In the present work, several organosilicas have been prepared by sol-gel procedures and post-functionalization methods. Some materials containing ruthenium alkylidenes were successfully tested in olefin metathesis reactions, whereas silica-supported prolinamides resulted in efficient chiral organocatalysts in asymmetric aldolizations (recycling up to 5 runs possible). Finally, the control of the morphologic and textural properties of self-assembled bridged silsesquioxanes was possible by adjusting the synthetic conditions in the hydrolytic polycondensation of silylated imidazolium salts containing urea functions.

Orientador: Marcos Nogueira Eberlin / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-14T14:25:38Z (GMT). No. of bitstreams: 1 Nachtigall_FabianeManke_D.pdf: 3920782 bytes, checksum: 88d49f1c9eaf6b17b3567019b6df9444 (MD5) Previous issue date: 2009 / Resumo: Com o objetivo de entender as propriedades intrínsecas dos líquidos iônicos imidazólios, foram desenvolvidos trabalhos de investigação dos mecanismos de dissociação e destilação, força intrínseca de ligações de hidrogênio e formação e caracterização de carbenos a partir destes compostos. Tais estudos foram realizados através da espectrometria de massas com técnicas API (Atmospheric Pressure Ionization) como ESI-MS(/MS) (Eletrospray Ionization Mass Spectrometry) e APCI-MS(/MS) (Atmospheric Pressure Chemical Ionization Mass Spectrometry) que são técincas de ionização branda que permitem a análise dos compostos por infusão direta da solução de interesse. Para estes estudos foram escolhidos cátions imidazólios com diferentes substituintes nas posições N-1, N-3 e C-2, além de diferentes ânions como contra-íons. O objetivo do trabalho foi testar como essas modificações na cadeia iriam afetar as porpriedades intrínsecas estudadas. A partir dos resultados obtidos nos trabalhos realizados foi possível propor mecanismos de fragmentação para uma vasta gama de líquidos iônicos imidazólios, e propor um mecanismo de destilação para alguns destes compostos. Foram realizadas medidas onde foi possível ordenar e medir a magnitude intrínseca das ligações de hidrogênio para diferentes cátions. Além disso foram obtidas informações a respeito da formação e caracterização de carbenos a partir de líquidos iônicos di, tri e tetraimidazólios. / Abstract: In order to understand the intrinsic properties of imidazolium ionic liquids, studies of dissociation and distillation mechanisms were developed. The intrinsic strength of hydrogen bonds and formation and characterization of carbenes from these compounds were also investigated. Such studies were conducted by API (Atmospheric Pressure Ionization) mass spectrometry techniques such as ESI-MS(/MS) (Electrospray Ionization Mass Spectrometry) and APCI-MS(/MS) (Atmospheric Pressure Chemical Ionization Mass Spectrometry) which are soft ionization techniques allowing the analysis of compounds by direct infusion of the solution of interest. For these studies, imidazolium cations with different substituent at positions N-1, N-3 and C-2 and different anions as counter ions were selected. The objective was to test how these changes in the chains would affect the intrinsic properties studied. From the results of the work fragmentation mechanisms for a wide range of imidazolium ionic liquids were proposed, as well as a mechanism for the distillation of some of these compounds. Measurements were made to order the intrinsic strength of hydrogen bonding for different cations. Further information was obtained about the formation and characterization of carbenes from di-, tri-and tetra-imidazolium ionic liquids. / Doutorado / Quimica Organica / Doutor em Ciências

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.

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