No description available.

No description available.

por fatores químicos e físicos, promovendo infecções hospitalares relacionadas ao uso de cateteres e demais instrumentos hospitalares, elevando os índices de mortalidade e morbidade de pacientes. Portanto, garantir a correta desinfecção capaz de impedir contaminações e infecções em ambientes hospitalares é de extrema importância. Para este fim, neste estudo explorou-se a seleção de uma substância capaz de marcar e ser biocida contra biofilmes fúngicos em superfícies de aço inox, a partir de nove candidatos benzimidazóis fluorescentes, com códigos NB1 a NB9 e oito sais imidazólicos de corantes azóicos, denominados C4MImErioCr, C10MImMO, C16MImMO, (C10)2MImMO, C4MImMO, C10MImORANGEII, C16MImORANGEII e (C10)2MImORANGEII. Desenvolveu-se para este fim um roteiro metodológico para determinar quais destas substancias são capazes de marcar e eliminar biofilmes de forma eficaz e segura. Os métodos utilizados para avaliar as substâncias foram (1) a Concentração Mínima Inibitória (MIC) conforme protocolo do CLSI M27-A3, (2) microscopias verificando capacidade das substâncias em marcar células, (3) ensaios com deposição sobre superfície do corpo de prova (placas de aço inox) com biofilme, (4) verificação da atividade biocida sobre biofilmes utilizando microscopias e (5) ensaios de citotoxicidade. Essas substâncias foram testadas frente a nove cepas de Candida spp., incluindo C. tropicalis, C. albicans e C. parapsilosis Na avaliação das substâncias, SI de corantes azóicos inibiram o crescimento celular de fungos, já o benzimidazol fluorescente NB7 apresentou atividades simultâneas de detecção e ação biocida sobre o biofilme. Todas as cepas testadas foram sensíveis a essa substância. Além disso, os biofilmes formados pelas cepas ATCC 18804 (C. albicans,) ATCC 22019 (C. parapsilosis) e ATCC 750 (C. tropicalis) na superfície de aço inox 304 sofreram ação biocida, quando expostas por 15 segundos a NB7, sendo um potencial sanitizante. / Biofilms provide an environment capable of protecting microbial cells from damage by chemical and physical factors of the immune system, and hinder the penetration of various antimicrobial agents, promoting nosocomial infections related to catheters, increasing mortality and morbidity of patients. Therefore, it is important to ensure proper hygiene to prevent contamination and infections in hospital environments. For this purpose, this study explored the identification of a substance that both detects and have biocide activity against fungal biofilms on stainless steel surfaces. Both nine fluorescent benzimidazole substances, coded NB1 to NB9 and eight imidazolium salts of azo dyes, named denominados C4MImErioCr, C10MImMO, C16MImMO, (C10)2MImMO, C4MImMO, C10MImORANGEII, C16MImORANGEII e (C10)2MImORANGEII were tested as candidates. These substances were tested applying a methodology developed to determine if a substance is able detecting and have biocide activity against fungal biofilms. Overall, this study involved the following methods: (1) Minimum Inhibitory concentration test following the CLSI protocol (M27-A3; the substances were tested against nine fungal strains, including C. tropicalis, C. albicans and C. parapsilosis.), (2) microscopy to determine the marker capacity, (3) spraying tests of the substances on surfaces (stainless steel) with fungal biofilms, (4) tests to verify the capability of the substances to both stain and were biocide against fungal biofilms, applying microscopic techniques and (5) cytotoxicity tests Within the set of seventeen substances, benzimidazole derivative NB7 was identified with the desired capabilities, staining and biocide activity against fungal biofilms at the same time. All tested fungal strains were sensible to this substance. A biocide activity was identified on the biofilms of ATCC 18804 (C. albicans), ATCC 22019 (C. parapsilosis) and ATCC 750 (C .tropicalis), grown on stainless steel 304, when exposed fifteen seconds to substance NB7. Although this substance showed being cytotoxic, it represents a promising candidate for sanitization purposes, including medical tools.

por fatores químicos e físicos, promovendo infecções hospitalares relacionadas ao uso de cateteres e demais instrumentos hospitalares, elevando os índices de mortalidade e morbidade de pacientes. Portanto, garantir a correta desinfecção capaz de impedir contaminações e infecções em ambientes hospitalares é de extrema importância. Para este fim, neste estudo explorou-se a seleção de uma substância capaz de marcar e ser biocida contra biofilmes fúngicos em superfícies de aço inox, a partir de nove candidatos benzimidazóis fluorescentes, com códigos NB1 a NB9 e oito sais imidazólicos de corantes azóicos, denominados C4MImErioCr, C10MImMO, C16MImMO, (C10)2MImMO, C4MImMO, C10MImORANGEII, C16MImORANGEII e (C10)2MImORANGEII. Desenvolveu-se para este fim um roteiro metodológico para determinar quais destas substancias são capazes de marcar e eliminar biofilmes de forma eficaz e segura. Os métodos utilizados para avaliar as substâncias foram (1) a Concentração Mínima Inibitória (MIC) conforme protocolo do CLSI M27-A3, (2) microscopias verificando capacidade das substâncias em marcar células, (3) ensaios com deposição sobre superfície do corpo de prova (placas de aço inox) com biofilme, (4) verificação da atividade biocida sobre biofilmes utilizando microscopias e (5) ensaios de citotoxicidade. Essas substâncias foram testadas frente a nove cepas de Candida spp., incluindo C. tropicalis, C. albicans e C. parapsilosis Na avaliação das substâncias, SI de corantes azóicos inibiram o crescimento celular de fungos, já o benzimidazol fluorescente NB7 apresentou atividades simultâneas de detecção e ação biocida sobre o biofilme. Todas as cepas testadas foram sensíveis a essa substância. Além disso, os biofilmes formados pelas cepas ATCC 18804 (C. albicans,) ATCC 22019 (C. parapsilosis) e ATCC 750 (C. tropicalis) na superfície de aço inox 304 sofreram ação biocida, quando expostas por 15 segundos a NB7, sendo um potencial sanitizante. / Biofilms provide an environment capable of protecting microbial cells from damage by chemical and physical factors of the immune system, and hinder the penetration of various antimicrobial agents, promoting nosocomial infections related to catheters, increasing mortality and morbidity of patients. Therefore, it is important to ensure proper hygiene to prevent contamination and infections in hospital environments. For this purpose, this study explored the identification of a substance that both detects and have biocide activity against fungal biofilms on stainless steel surfaces. Both nine fluorescent benzimidazole substances, coded NB1 to NB9 and eight imidazolium salts of azo dyes, named denominados C4MImErioCr, C10MImMO, C16MImMO, (C10)2MImMO, C4MImMO, C10MImORANGEII, C16MImORANGEII e (C10)2MImORANGEII were tested as candidates. These substances were tested applying a methodology developed to determine if a substance is able detecting and have biocide activity against fungal biofilms. Overall, this study involved the following methods: (1) Minimum Inhibitory concentration test following the CLSI protocol (M27-A3; the substances were tested against nine fungal strains, including C. tropicalis, C. albicans and C. parapsilosis.), (2) microscopy to determine the marker capacity, (3) spraying tests of the substances on surfaces (stainless steel) with fungal biofilms, (4) tests to verify the capability of the substances to both stain and were biocide against fungal biofilms, applying microscopic techniques and (5) cytotoxicity tests Within the set of seventeen substances, benzimidazole derivative NB7 was identified with the desired capabilities, staining and biocide activity against fungal biofilms at the same time. All tested fungal strains were sensible to this substance. A biocide activity was identified on the biofilms of ATCC 18804 (C. albicans), ATCC 22019 (C. parapsilosis) and ATCC 750 (C .tropicalis), grown on stainless steel 304, when exposed fifteen seconds to substance NB7. Although this substance showed being cytotoxic, it represents a promising candidate for sanitization purposes, including medical tools.

por fatores químicos e físicos, promovendo infecções hospitalares relacionadas ao uso de cateteres e demais instrumentos hospitalares, elevando os índices de mortalidade e morbidade de pacientes. Portanto, garantir a correta desinfecção capaz de impedir contaminações e infecções em ambientes hospitalares é de extrema importância. Para este fim, neste estudo explorou-se a seleção de uma substância capaz de marcar e ser biocida contra biofilmes fúngicos em superfícies de aço inox, a partir de nove candidatos benzimidazóis fluorescentes, com códigos NB1 a NB9 e oito sais imidazólicos de corantes azóicos, denominados C4MImErioCr, C10MImMO, C16MImMO, (C10)2MImMO, C4MImMO, C10MImORANGEII, C16MImORANGEII e (C10)2MImORANGEII. Desenvolveu-se para este fim um roteiro metodológico para determinar quais destas substancias são capazes de marcar e eliminar biofilmes de forma eficaz e segura. Os métodos utilizados para avaliar as substâncias foram (1) a Concentração Mínima Inibitória (MIC) conforme protocolo do CLSI M27-A3, (2) microscopias verificando capacidade das substâncias em marcar células, (3) ensaios com deposição sobre superfície do corpo de prova (placas de aço inox) com biofilme, (4) verificação da atividade biocida sobre biofilmes utilizando microscopias e (5) ensaios de citotoxicidade. Essas substâncias foram testadas frente a nove cepas de Candida spp., incluindo C. tropicalis, C. albicans e C. parapsilosis Na avaliação das substâncias, SI de corantes azóicos inibiram o crescimento celular de fungos, já o benzimidazol fluorescente NB7 apresentou atividades simultâneas de detecção e ação biocida sobre o biofilme. Todas as cepas testadas foram sensíveis a essa substância. Além disso, os biofilmes formados pelas cepas ATCC 18804 (C. albicans,) ATCC 22019 (C. parapsilosis) e ATCC 750 (C. tropicalis) na superfície de aço inox 304 sofreram ação biocida, quando expostas por 15 segundos a NB7, sendo um potencial sanitizante. / Biofilms provide an environment capable of protecting microbial cells from damage by chemical and physical factors of the immune system, and hinder the penetration of various antimicrobial agents, promoting nosocomial infections related to catheters, increasing mortality and morbidity of patients. Therefore, it is important to ensure proper hygiene to prevent contamination and infections in hospital environments. For this purpose, this study explored the identification of a substance that both detects and have biocide activity against fungal biofilms on stainless steel surfaces. Both nine fluorescent benzimidazole substances, coded NB1 to NB9 and eight imidazolium salts of azo dyes, named denominados C4MImErioCr, C10MImMO, C16MImMO, (C10)2MImMO, C4MImMO, C10MImORANGEII, C16MImORANGEII e (C10)2MImORANGEII were tested as candidates. These substances were tested applying a methodology developed to determine if a substance is able detecting and have biocide activity against fungal biofilms. Overall, this study involved the following methods: (1) Minimum Inhibitory concentration test following the CLSI protocol (M27-A3; the substances were tested against nine fungal strains, including C. tropicalis, C. albicans and C. parapsilosis.), (2) microscopy to determine the marker capacity, (3) spraying tests of the substances on surfaces (stainless steel) with fungal biofilms, (4) tests to verify the capability of the substances to both stain and were biocide against fungal biofilms, applying microscopic techniques and (5) cytotoxicity tests Within the set of seventeen substances, benzimidazole derivative NB7 was identified with the desired capabilities, staining and biocide activity against fungal biofilms at the same time. All tested fungal strains were sensible to this substance. A biocide activity was identified on the biofilms of ATCC 18804 (C. albicans), ATCC 22019 (C. parapsilosis) and ATCC 750 (C .tropicalis), grown on stainless steel 304, when exposed fifteen seconds to substance NB7. Although this substance showed being cytotoxic, it represents a promising candidate for sanitization purposes, including medical tools.

The convergence of supramolecular and polymer sciences has led to the construction of analogs of traditional covalently-constructed polymeric structures and architectures by supramolecular methods. Host-guest complexations of polymers are also possible through well-defined synthesis of polymeric building blocks, for novel supramolecular polymers. Monotopic polymeric building blocks were synthesized by controlled radical polymerizations with a crown or paraquat initiator. The combinations of terminal and central functionalities of host and guest polymeric building blocks provided chain-extended and tri-armed homopolymers, and diblock and tri-armed copolymers. A supramolecular graft copolymer was formed from a main-chain poly(ester crown ether) and a paraquat terminated polystyrene. This comb-like copolymer was characterized by a large viscosity increase. A four-armed polystyrene-b-poly(n-butyl methacrylate) was synthesized from a pseudorotaxane macroinitiator derived from a complex of a crown-centered polystyrene and a dufunctional paraquat compound. A single peak with higher molecular weight from size exclusion chromatography proved the copolymer formation. Supramolecular interactions enhance the ionic conductivity of semi-crystalline ionic polymers; the ionic conductivity of a C₆-polyviologen and dibenzo-30-crown-10 mixture was 100 times higher than the polyviologen itself. However, ionic conductivities of amorphous polyviologens with polyethers were influenced only by glass transition temperature changes. New imidazolium ionic liquid monomers and imidazolium based polymers were synthesized for potential applications in electroactive devices, such as actuators. Structure-property relationships for pendant imidazolium polyacrylates and main-chain imidazolium polyesters were investigated. Terminal ethyleneoxy moeties enhanced ionic conduction 2~3 times; however, the alkyl chain length effect was negligible. For the imidazoium polyesters, higher ion conductivities result from 1) mono-imidazolium over bis-imidazolium, and 2) bis(trifluoromethanesulfonyl)imide polymers over hexafluorophosphate analogs. A semi-crystalline hexafluorophosphate polyester with C₁₀-sebacate-C₁₀, displayed 400-fold higher ionic conductivity than the amorphous C₆-sebacate-C₆ analogue, suggesting the formation of a biphasic morphology in the former polyester. New dicationic imidazolium salts have interesting features. 1,2-Bis[N-(N'-alkylimidazoilum)]ethane salts stack well in the solid state and possess multiple solid-solid phase transitions. They complex with dibenzo-24-crown-8 and a dibenzo-24-crown-8 based pyridyl cryptand with <i>K_a</i> = ~30 and 360 M¹, respectively. Some of these dicationic imidazolium salts have low entropies of fusion, typical of plastic crystals. These newly discovered imidazolium homopolymers have ionic conductivities up to 10⁴ (S cm⁻¹); however, better properties are still required. Well-designed block copolymers should provide both good electrical and mechanical properties from bicontinuous morphologies, such ion channels. / Ph. D.

Le motif imidazole, un hétérocycle à 5 atomes contenant 2 atomes d’azote et trois atomes de carbone, présente des propriétés physico-chimiques intéressantes qui en font un composé de choix pour plusieurs applications. Parmi ces propriétés, la fonctionnalisation simple des deux atomes d’azote pour former un sel d’imidazolium est très intéressante. Ces sels sont d’excellents précurseurs de carbènes N-hétérocycliques (NHC) et sont couramment utilisés pour synthétiser des ligands en vue d’une utilisation en catalyse organométallique. D’autre part, cette famille de composés possède des propriétés anionophores permettant une utilisation en transport anionique. Le présent travail contient les résultats de travaux concernant ces deux domaines, soit la catalyse et le transport anionique. Dans un premier temps, les propriétés de dérivés de l’imidazole sont exploitées pour former un catalyseur de type palladium-NHC qui est utilisé pour catalyser la réaction de Suzuki-Miyaura en milieu aqueux. L’efficacité de ce catalyseur a été démontrée en utilisant aussi peu que 0,001 mol% pour un rendement quantitatif. Il s’agit de la première occurrence d’un processus hétérogène et recyclable dans l’eau, utilisant un catalyseur de type Pd-NHC et qui ne nécessite aucun additif ou co-solvant. Le recyclage a été prouvé jusqu’à 10 cycles sans diminution apparente de l’activité du catalyseur. Dans un second temps, plusieurs sels d’imidazolium ont été testés en tant que transporteurs transmembranaires d’anions chlorures. Les propriétés intrinsèques des sels utilisés qui en font des transporteurs efficaces ont été élucidées. Ainsi, les paramètres qui semblent affecter le plus le transport anionique sont le changement du contre-anion du sel d’imidazolium de même que la propension de ce dernier à s’auto-assembler via une succession d’empilements-π. De plus, les propriétés du transport ont été élucidées, montrant la formation de canaux transmembranaires qui permettent non-seulement la diffusion d’ions Cl-, mais aussi le transport de protons et d’ions Ca2+. L’intérêt de cette recherche repose d’abord dans le traitement de diverses pathologies voyant leur origine dans le dysfonctionnement du transport anionique. Cependant, les propriétés bactéricides des sels d’imidazolium utilisés ont été identifiées lors des dernières expériences. / The imidazole moiety is a 5-membered heterocyclic ring, containing 2 nitrogen atoms and 3 carbon atoms. It possesses interesting physico-chemical properties that make it an interesting choice for various uses. One of its most interesting properties is structural versatility, accessible by the simple alkylation of the two nitrogen atoms leading to the formation of an imidazolium salt. These salts are excellent N-heterocyclic carbene (NHC) precursors and are frequently used to synthesize ligands used in organometallic catalysis. In addition, imidazolium salts possess anionophoric properties, allowing their use in anion transmembrane transport. The current work contains the results of research in these two fields: catalysis and anion transport. First, the properties of imidazole derivatives were used to synthesize a palladium-NHC catalyst that was used for the Suzuki-Miyaura coupling in neat water. The efficiency of this catalyst was demonstrated by using loading as low as 0,001 mol% to get quantitative yields. It is the first occurrence of a heterogeneous and recyclable process in neat water using a NHC-Pd catalyst without the need to use either a co-solvent or an additive. The recycling was demonstrated by performing 10 consecutive runs of the reaction, without observing any diminishing of the catalyst’s activity. Second, many imidazolium salts were tested as transmembrane chloride anion carriers. The intrinsic properties of these salts that make them potent anion transporters were elucidated. Specifically, small modifications to the structure of these salts turned out to allow better self-association by π-stacking interactions and to increase their activity. Similarly, changing the counter-anion of these salts affected their transport effectiveness. Moreover, the transport properties were studied and showed the formation of transmembrane channels that allow the diffusion of chloride anions, but also of protons and calcium ions. The interest of this research lies in the possible treatment of various pathologies that originate from faulty anion transport. In addition, the bactericidal properties of imidazolium salts were also identified and may prove useful in the future work.

L’éclosion de bactéries résistantes aux antibiotiques constitue un problème sérieux auquel fait face notre système de santé. L’une des stratégies récemment proposées afin de s’attaquer efficacement et irréversiblement à ces microorganismes multi-résistants est de cibler directement leur membrane via l’action de molécules induisant un débalancement électrolytique de part et d’autre de cette dernière. Parallèlement, ces mêmes agents peuvent aussi avoir des applications dans le traitement de maladies originant des dysfonctions du transport ionique, comme la fibrose kystique. À cet égard, nous présentons dans cette thèse différents sels d’imidazolium et benzimidazolium N,N-disubstitués possédant un potentiel à la fois antimicrobien et ionophore. Notre approche se résume d’abord en un volet mécanistique où une série de modifications structurelles ont été apportées à des sels d’imidazolium et benzimidazolium afin d’observer comment ces changements modulent l’efficacité du transport d’anions dans la membrane artificielle d’un liposome. Nous avons à ce titre pu conclure que l’espèce formée de deux bras aromatiques phényléthynylbenzyl, disposées symétriquement de part et d’autre d’un cation imidazolium, induisait le meilleur transport des anions chlorures, au travers d’une membrane de liposomes, à des concentrations de l’ordre du micromolaire. En outre, les monocations imidazolium et benzimidazolium flanqués d’un contre-anion bis(trifluorométhylsulfonyl)amide ont conduit à une activité ionophore plus rapide. Qui plus est, en s’appuyant sur ces résultats, nous avons présenté le premier exemple, à notre connaissance, d’un transporteur d’anions et de cations, contenant le cation benzimidazolium et capable d’agir aussi bien dans des liposomes que dans des bactéries. Dans un second temps, les meilleurs agents ionophores ont été étudiés dans les membranes plus complexes des bactéries et des globules rouges humains pour vérifier leur effet bactéricide et leur innocuité. Le design de nos transporteurs formés d’un espaceur luthidine a ainsi permis d’obtenir un agent antimicrobien efficace dans des bactéries gram positives et négatives (B. thuringiensis et E. coli) avec une toxicité limitée de l’ordre de 10% sur les globules rouges humains à ses concentrations bactéricides. / The emergence of antibiotic resistant bacteria is a serious problem that our health system faces. One recently proposed strategy to effectively and irreversibly kill these multi-resistant microorganisms is to directly target the integrity of their membrane, using small molecules able to induce an electrolyte imbalance. Moreover, the same molecules may find applications in the treatement od diseases originating from the dysfunction of ion transport, such as cystic fibrosis. Herein we present different imidazolium and benzimidazolium salts N,N-disubstituted with both antimicrobial and ionophoric potential. We first performed mechanistic studies where different structural changes have been made to the imidazolium and benzimidazolium salts to observe how these modifications modulate the efficiency of the anion transport in artificial membrane liposomes. We were able to conclude that the species formed of two aromatic arms phenylethynylbenzyl arranged symmetrically on either side of an imidazolium cation, induced a better transport of chloride anions, through a membrane of liposomes at the micromolar range. In addition, monocations imidazolium and benzimidazolium flanked with an bis(trifluorométhylsulfonyl)amide anion led to faster ionophore activity. Moreover, based on these results we presented the first example, to our knowledge, for an anions and cations benzimidazolium-based transporter, acting as well in liposomes as in bacteria. Secondly, the best anionophore agents were analyzed in more complex bacterias and human red blood cells membranes to study their bactericidal potential and innocuity. Among all the benzimidazolium salts studied, we identified one compound, which presents interesting antibacterial properties as a result of its ability to induce an electrolytic imbalance and to disrupt the integrity and the potential of the bacterial membranes. At the same time this antibacterial agent presented a low toxicity to human cells in bacteriostatic range concentrations.

No description available.