New methodologies for the efficient syntheses of 4,4-difluoro-4-bora-3a,4adiaza- s-indacenes (BODIPYs) and rosamines were developed. A serendipitous discovery led to a new reaction which afforded BODIPYs in high yields. Systematic studies of the kinetics and mechanisms of the new reaction were performed. A series of BODIPYs were successfully prepared using the new approach. A simple and efficient synthesis of rosamines with cyclic-amine substituents was devised. These new rosamines showed interesting anti-tumor activities. Several types of novel fluorescent compounds were prepared. Highly fluorescent GFP-chromophore analogs were designed and synthesized. The correlation between the optical properties and the structures was investigated. New pyronin dyes with mesoheteroatom substituents were efficiently prepared. The fluorescence properties of these compounds were highly dependent on the nature of the meso-substituents. A set of BODIPY dyes that fluoresce brightly above 600 nm were made. They were then used as acceptors to prepare water-soluble through-bond energy transfer cassettes. All the cassettes had complete energy transfer and high quantum yields in MeOH. A few also had good fluorescence properties in aqueous media and even on proteins. The through-bond energy transfer cassettes were used to monitor protein-protein interactions. In order to test our hypothesis, an artificial protein interaction system was built by utilizing the biotin/(strept)avidin interactions. Thus Atto425-BSA-biotin, streptavidin-cassette1 and avidin-cassette2 were prepared. The interactions between Atto425-BSA-biotin and cassette labeled (strept)avidin were successfully detected in vitro and in living cells by fluorescence techniques.

O consumo de produtos da reação de Maillard (PRM) formados em alimentos contribui para o aumento dos níveis séricos de produtos finais de glicação avançada, que, por sua vez, estão associados à fisiopatologia e progressão do diabetes, de doenças cardiovasculares e neurodegenerativas. A formação de PRM em alimentos e sistemas modelo-alimento está bem documentada, mas informações sobre os efeitos de diferentes métodos de cocção e uso de receitas são escassas, especialmente para carne vermelha. É importante avaliar se o controle das condições de cocção domésticas pode afetar a formação de PRM em carne, um alimento amplamente consumido. O objetivo deste trabalho foi estudar a formação dos PRM: furosina, carboximetillisina, acrilamida e compostos fluorescentes em carne bovina submetida a técnicas de cocção por calor úmido e calor seco. Hambúrgueres com 50 g de coxão mole (Semimembranosus) moído e 1% de sal de cozinha foram grelhados e empanados e fritos até atingir as temperaturas internas: 60°, 70°, 80°, 90° e 100°C; cozidos por fervura em água até 60°, 70°, e 80°C; e assados a 180°, 240° e 300°C por 30 min. Os produtos da fase inicial da RM predominaram nas carnes grelhadas e empanadas e fritas em temperatura menor que 90 °C, acima de 90 °C ocorreu a degradação de furosina, associada à formação acentuada de compostos fluorescentes e a etapa intermediária da RM está em curso, predominantemente; a formação do marcador da fase avançada da RM (CML) ocorreu apenas na condição térmica mais severa, a carne assada a 300 °C por 30 minutos. Condições de cocção que resultaram em grande aceitação da cor e baixa formação de PRM de fase avançada foram encontradas para carne bovina e podem ser utilizadas em orientações para pacientes com diabetes em ensaios clínicos futuros. / The ingestion of Maillard reaction products (MRP) from foods seems to be correlated with serum advanced glycation end products (AGEs) levels in humans. AGEs are associated with pathological effects in vivo, specifically diabetes complications, cardiovascular and neurodegenerative diseases. Substantial amount of data about MRP content in individual food products and model systems can be found, but there is a lack of information regarding the MRP generation during home cooking, especially for red meat. It is of interest to evaluate whether the control of home cooking conditions can effectively affect MRP content in beef, a food consumed worldwide. The influence of home cooking methods employing dry-heat and boiling on the generation of furosine, carboxymethyllysine, acrylamide and fluorescent compounds in beef was investigated in this study. Fifty grams of raw ground meat (Semimembranosus) with 1.0% of NaCl was made into a hamburger shape and grilled or breaded and fried: meat was cooked to an internal temperature of 60°, 70°, 80°, 90° and 100°C; boiled: meat was cooked to 60°, 70°, and 80°C. For baking, the oven was set at 180°, 240° and 300°C for 30 minutes. Grilling and frying hamburgers to an internal temperature below 90 °C mainly generated furosine. When the temperature reached 90 °C and 100 °C, furosine content decreased and fluorescent compounds increased exponentially. Baking meat at 300 °C, the most severe heat treatment studied, resulted in the formation of carboxymethyllysine. Home cooking conditions leading to low MRP generation and pleasant colors were obtained and could be used to guide diabetic patients in clinical studies.

O consumo de produtos da reação de Maillard (PRM) formados em alimentos contribui para o aumento dos níveis séricos de produtos finais de glicação avançada, que, por sua vez, estão associados à fisiopatologia e progressão do diabetes, de doenças cardiovasculares e neurodegenerativas. A formação de PRM em alimentos e sistemas modelo-alimento está bem documentada, mas informações sobre os efeitos de diferentes métodos de cocção e uso de receitas são escassas, especialmente para carne vermelha. É importante avaliar se o controle das condições de cocção domésticas pode afetar a formação de PRM em carne, um alimento amplamente consumido. O objetivo deste trabalho foi estudar a formação dos PRM: furosina, carboximetillisina, acrilamida e compostos fluorescentes em carne bovina submetida a técnicas de cocção por calor úmido e calor seco. Hambúrgueres com 50 g de coxão mole (Semimembranosus) moído e 1% de sal de cozinha foram grelhados e empanados e fritos até atingir as temperaturas internas: 60°, 70°, 80°, 90° e 100°C; cozidos por fervura em água até 60°, 70°, e 80°C; e assados a 180°, 240° e 300°C por 30 min. Os produtos da fase inicial da RM predominaram nas carnes grelhadas e empanadas e fritas em temperatura menor que 90 °C, acima de 90 °C ocorreu a degradação de furosina, associada à formação acentuada de compostos fluorescentes e a etapa intermediária da RM está em curso, predominantemente; a formação do marcador da fase avançada da RM (CML) ocorreu apenas na condição térmica mais severa, a carne assada a 300 °C por 30 minutos. Condições de cocção que resultaram em grande aceitação da cor e baixa formação de PRM de fase avançada foram encontradas para carne bovina e podem ser utilizadas em orientações para pacientes com diabetes em ensaios clínicos futuros. / The ingestion of Maillard reaction products (MRP) from foods seems to be correlated with serum advanced glycation end products (AGEs) levels in humans. AGEs are associated with pathological effects in vivo, specifically diabetes complications, cardiovascular and neurodegenerative diseases. Substantial amount of data about MRP content in individual food products and model systems can be found, but there is a lack of information regarding the MRP generation during home cooking, especially for red meat. It is of interest to evaluate whether the control of home cooking conditions can effectively affect MRP content in beef, a food consumed worldwide. The influence of home cooking methods employing dry-heat and boiling on the generation of furosine, carboxymethyllysine, acrylamide and fluorescent compounds in beef was investigated in this study. Fifty grams of raw ground meat (Semimembranosus) with 1.0% of NaCl was made into a hamburger shape and grilled or breaded and fried: meat was cooked to an internal temperature of 60°, 70°, 80°, 90° and 100°C; boiled: meat was cooked to 60°, 70°, and 80°C. For baking, the oven was set at 180°, 240° and 300°C for 30 minutes. Grilling and frying hamburgers to an internal temperature below 90 °C mainly generated furosine. When the temperature reached 90 °C and 100 °C, furosine content decreased and fluorescent compounds increased exponentially. Baking meat at 300 °C, the most severe heat treatment studied, resulted in the formation of carboxymethyllysine. Home cooking conditions leading to low MRP generation and pleasant colors were obtained and could be used to guide diabetic patients in clinical studies.

L'objet de ce travail de thèse concerne la synthèse par réaction cascade pallado-catalysé d'une nouvelle famille de chromophores pentacycliques azotés dont les propriétés de fluorescence peuvent être modulées en fonction des groupements fonctionnels présents dans la molécule. Ces chromophores sont obtenus par réaction one-pot entre des acides 2-formyl boroniques et des 2,5-dihalopyridines. Le processus cascade est initié par un couplage de Suzuki suivi par deux cyclisations successives. La première se fait sur l'azote de la pyridine et la seconde se produit de façon régio-sélective sur le carbone adjacent à l'azote. Les structures cristallines et le calcul théorique DFT ont montré la régio et la stéréo-sélectivité de la réaction. De plus, des études préliminaires ont montré que ces composés polycycliques possèdent d'excellentes propriétés de fluorescence ainsi qu'une activité biologique qui devraient nous permettre d'étendre le champ d'application de ces nouveaux chromophores vers le domaine médical et l'électronique moléculaire / The aim of this work concerns the synthesis of a new family of aza-pentacyclic chromophore whose fluorescence properties can be modulated according to the functional groups present in the molecule. These chromophores were obtained through a cascade process between 2-formylbenzene boronic acid and 2,5-dihalopyridines. The cascade process is initiated by a palladium-catalyzed cross-coupling reaction and is followed by two successive nucleophilic cyclizations; the first cyclization performed on the pyridine nitrogen and the second occurred regioselectively on the adjacent carbon atom. This new cascade reaction allowed the formation of a pentacycle as a single regioisomer with four new bonds and two contiguous stereocenters with trans relationships. In addition, preliminary studies have shown that these polycyclic compounds have excellent fluorescence properties as well as biological properties that should enable us to extend the scope of these new chromophores to the medical field and molecular electronics