Diverse dendrimer peripheries are often produced through convergent synthesis with multiple protection-deprotection steps. Achieving such diversity while maintaining monodispersity, has previously proven problematic. Interception of an electrophilic poly(monochlorotriazine) dendrimer with a molecule of interest bearing a reactive, nucleophilic group presents an efficient method to achieve large quantities of dendrimers with biologically relevant peripheries. Kilogram-scale synthesis of a triazine-based dendrimer relies on reaction of the dichlorotriazine monomer with the amine terminated dendrimer to afford a poly(monochlorotriazine) dendrimer. Normally, the dendrimer is then reacted with piperidine, an inexpensive “cap” due to its chemically inert nature after reaction. The dendrimer then undergoes a global deprotection to afford an amine-terminated dendrimer. Subsequent iterations with the dichlorotriazine monomer affords higher generation architectures. Intercepting the poly(monochlorotriazine) dendrimer with biologically relevant molecules containing reactive amines enables the development of a drug delivery vehicle. Desferrioxamine B, an iron chelate, and camptothecin, and anticancer drug, are two clinically approved drugs of interest investigated for macromolecular drug delivery. Upon acylation of each drug with BOC-isonipecotic acid, substitution on the dendrimer may occur with varying levels of success depending on the drug in question. Upon successful substitution to afford the desired product,biological studies may be performed. Each synthetic approach will be discussed along with alternative routes leading to this general strategy.

Dendrimers are a unique class of macromolecules that present perfect branching on a molecular scale. The pattern of branching at the atomic scale is compared to the branching of trees, from whence dendrimers get their name. Dendrimers have been attractive synthetic targets for the past twenty years. The methods and building blocks used in the synthesis of dendrimers vary, but molecules of this class of polymeric materials all possess symmetrical branching emanating from the core. At each branch point the number of groups increases exponentially. Efforts directed toward the synthesis of dendrimers presenting multiple functional groups at the surface and within the dendrimer structure are described. Methods are described which provide access to dendrimers in a one-pot per generation fashion, with triazines as the common moiety. Chemoselective routes utilize the temperature dependant substitution of cyanuric chloride to construct dendrimers, obviating the use of protected monomers or the need to manipulate functional groups during the synthesis. These methods are atom economical, as the only by-products are HCl and a base to scavenge it. The methods are efficient, with typical isolated yields of product in the middle to high ninety percent range, often on a multi-gram scale. Methods are described for conducting three separate reactions in a single pot. Specific emphasis is placed on structural control of the interior and surface groups of the dendrimers. The synthesis of a G3 dendrimer of layered composition is described. The use of a different difunctional linkage group for each generation of dendrimer growth produced a G3 dendrimer with layered composition without the use of protecting groups or functional group interconversions. A G3 dendrimer was synthesized presenting five different functionalities at the periphery on a 10 gram scale, resulting in approximately 70% overall yield. The peripheral groups are composed of orthogonal functionality, which can be independently and selectively unmasked or manipulated in the presence of the other functionality. The syntheses of dendrimers incorporating the short linker hydrazine produce materials with interesting physical properties as well as a low ratio of carbon to nitrogen. The use of dendrimers in the construction of novel macromolecular constructs is also described.

Previous monitoring studies by federal agencies such as the United States Geological Survey have shown that environmental contaminants rarely occur as single compounds but, rather, as mixtures. In aquatic ecosystems, mixtures of these compounds are often complex, sometimes containing dozens of compounds across a number of different chemical classes. Non-target aquatic organisms are frequently exposed to varying levels of contaminants based upon the physical properties of the chemicals, such as water solubility, and life-cycle habits of the individual organisms. In addition to this, past research has indicated that the presence of one class of contaminant may have an influence on the toxicities of other chemical classes. Water-only toxicity testing has historically provided a means by which researchers can rapidly determine the toxic effects of water-soluble compounds such as triazine herbicides and organophosphate insecticides. However, many legacy pesticides, such as organochlorine, and some current-use pesticides, such as pyrethroids, are strongly hydrophobic, and suspended or bedded sediments, rather than water, would generally be more appropriate matrices for monitoring. Yet sampling of sediments and quantification of residues of these pesticides is often lacking. Similarly, there have been few studies examining the toxicity of mixtures of these compounds in sediment. The first goal of this research was to examine the effects of select triazine herbicides on organophosphate insecticide toxicity utilizing water-only toxicity test with the aquatic amphipod Hyalella azteca. The second goal was to analyze an existing database of chemical concentrations using a toxicity-based screening approach in order to estimate the environmental hazard posed by mixtures of pyrethroid, organochlorine, and organophosphate insecticides in sediment to H. azteca. The third goal of this research was to examine the toxic effects of mixtures of different pyrethroid insecticides to H. azteca using compounds identified as most relevant from the screening phase of the study. The fourth goal of this research was to examine how pyrethroid and organochlorine insecticides partition between different size fractions within sediment and detritus, as well as between sediments with differing organic carbon content, and the resulting effects to compound toxicity and bioavailability. The final goal of this research was to examine potential modifications to bifenthrin sediment partitioning, toxicity, and bioaccessibility resulting from various dissolved salt concentrations in overlying water using H. azteca and Chironomus dilutus as reference organisms. Together, the individual objectives of this study provide a thorough and multi-tiered approach to determining the occurrence, environmental fate, biological effects, and bioavailability of frequently detected and co-occurring environmental contaminants in both agricultural and urban landscapes.

Made available in DSpace on 2014-06-11T19:32:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-07-06Bitstream added on 2014-06-13T19:21:44Z : No. of bitstreams: 1 vieira_vc_dr_jabo.pdf: 991037 bytes, checksum: 6e39ae9e1779bebf699c04fe2aa8cca6 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / As plantas daninhas da família Poaceae são as principais plantas que infestam a cultura de cana-de-açúcar. As espécies de gramíneas conhecidas por capim-colchão, estão entre as de maior ocorrência nas lavouras de cana-de-açúcar no Brasil. Atualmente o uso do controle químico está sendo o mais empregado para controle de Digitaria, porém há alguns relatos de falha no controle, principalmente com referência a herbicidas pertencentes ao grupo das triazinas, que bloqueiam a cadeia fotossintética, no fotossistema. As técnicas moleculares estão sendo bem recomendadas para análise da diversidade genética em plantas daninhas. Para a caracterização molecular vinte iniciadores foram utilizados para o RAPO e, para o PCR¬RFLP utilizou-se de dois iniciadores específicos P1 e P2 e a enzima de restrição Mael. O seqüenciamento foi realizado com o amplicom produzido com os iniciadores P1 e P2. Para o tratamento químico utilizou-se a ametrina. Com isso, esse trabalho teve como objetivos: caracterizar dez acessos de Digitaria spp. por marcadores RAPO e PCR¬RFLP, sequenciar uma região conservada do gene psbA e verificar possíveis associações entre o polimorfismo desse gene e a resposta fenotípica à ametrina. Pela análise molecular não houve variabilidade genética entre os acessos e todos apresentaram a mesma resposta fenotípica ao herbicida utilizado. Com esses resultados, concluiu-se que o capim-colchão dos dez acessos estudados pertence à espécie Digitaria nuda e não foi observada relação entre a ocorrência de polimorfismo e a suscetibilidade à ametrina, provavelmente porque todos os acessos estudados foram controlados na dose recomendada do herbicida. / The weed of family Peaceae are the most important infesting sugarcane crop plants. The gramineous species known as crabgrass are among the ones with high occurrence in Brazil sugarcane crop. Presently the use of chemical control is being the most common way used for the control of Digitaria, but with few controlling occurrences fails, with emphasis for those herbicides belonging to triazine group which block the photosynthetic chain at the photosystem II leveI. Molecular techniques are being recommended for the analysis of the genetic diversity such weed. For the molecular characterization twenty primers were used for RAPO and for the PCR¬RFLP a set of two specific primers P1 and P2 were used together with restriction enzyme Mael. The ONA sequencing was performed with an amplicon sample produced with the primers P1 and P2. For the chemical treatment control ametryn was selected. Thus this work had objectives as follows: to characterize ten accessions of Digitaria spp. by RAPO and PCR-RFLP markers, and to sequence a conserved region of the psbA gene so as to investigate the possible polymorphic associations of this gene in response to the phenotypic response to ametryn. For the molecular analysis it did not have genetic variability among the accessions and all had presented the same phenotypic response to the used herbicide. Based on the obtained results, it is concluded the crabgrass that ten collected accessions belong to the species Digitaria nuda, and it was not observed any relation among the polymorphism and susceptibility to ametryn probably because all the studied accessions had been controlled in the recommended dose of the herbicide.

Techn. Universiẗat, Diss., 2003--Darmstadt.

La nouvelle technologie innovatrice OLEDs (diodes organiques électroluminescentes) ne cesse de susciter l'engouement des scientifiques ainsi que les recherches à leurs égards. Ces dispositifs à base de matériaux organiques s'appliquent dans quasiment tous les domaines tels que l'éclairage, l'affichage...Une découverte récente vient d'apporter sa pierre à l'édifice en mettant au point une nouvelle troisième génération d'OLEDs. Cette révélation consiste en la réduction du coût des matériaux des OLEDs en utilisant des matériaux peu onéreux dits à fluorescence retardée. C'est dans cette optique que s'inscrit ce travail de thèse qui porte sur l'étude de ce type de matériaux pour les applications dans les OLEDs. Cette thèse est décomposée en deux principales parties. Dans un premier temps, nous avons étudié et synthétisé des matériaux pour cette nouvelle génération d'OLED en se basant sur un modèle de molécules existant. Ce dernier représente des dérivés de triazine-carbazole connus pour leurs propriétés adéquates aux OLEDs. Cette étude a démontré pour la première fois le caractère de fluorescence retardée de ces molécules. Nous avons par la suite caractérisé ces molécules au sein des OLEDs. Les résultats montrent l'efficacité de ces molécules. Dans un deuxième temps nous nous sommes intéressés à l'étude de molécules innovantes. Ainsi, des molécules dotées de fluorescences retardées et innovantes ont été synthétisées. Cette synthèse a été effectuée par une méthode très avantageuse. Par ailleurs, la structure et propriétés de ces molécules indiquent qu'elles sont dotées de fluorescences retardées. Ainsi, il est important de poursuivre ce travail, en évaluant les propriétés de ces molécules synthétisées, ainsi que de les caractériser au sein des OLEDs. / Recently, the synthesis of free metal materials for organic LEDs by Uoyama et al adds a third kind of luminescence, named thermally activated delayed fluorescence (TADF). The added value of this discovery is to lower significantly OLED cost thanks to the metal-free structure of these so-called hyper-fluorescent molecules. This work reports on this recent discovery in OLED's. We first studied the thermally activated delayed fluorescence from an existing molecular model. The latter, fulfil the condition of the delayed fluorescence and are based from triazine-carbazole derivatives. The results revealed for thefirst time the exhibition of the delayed fluorescence from this existing model. In a second part, a novel hyperfluorescent molecule have been synthesized following the design rules for the delayed fluorescence molecules. The synthesis was done by a method based on an attractive process. Furthermore, the structure and properties of these new materials indicate that these molecules are expected to exhibit delayed fluorescent. Thus, it is important to continue this work by evaluating the properties of these molecules and the OLEDs made from these materials.

Parmi tous les neurotransmetteurs identifiés à ce jour, la sérotonine (5-hydroxytryptamine, 5-HT) est impliquée dans le système le plus complexe de récepteurs. Parmi eux, les récepteurs 5-HT7 qui sont les derniers découverts (1993) semblent avoir des implications multiples tant au niveau central que périphérique. Le potentiel thérapeutique représenté par la découverte de ligands 5-HT7 sélectifs vis-à-vis d’autres RCPGs a motivé notre projet de recherche. Nos études sont orientées vers la conception de trois classes distinctes de ligands. Une première famille à été conçue sur une charpente benzimidazolone. Diverses pharmacomodulations ont permis un changement du profil d’activité de 5-HT1A vers 5-HT7. Une deuxième famille de composés à structure furo- ou pyrano[2,3-b] pyridinique constitue des analogues azotés d’un des plus intéressants agonistes sélectifs 5-HT7 actuels. La synthèse de ces dérivés a été conduite via la mise en oeuvre d’une étape clé de cycloaddition intramoléculaire de Diels-Alder à partir de 1,2,4-triazines judicieusement fonctionnalisées en 3 par une chaine aminoalkynol. Cette méthodologie nous a permis de faire varier les substituants alkyle de l’amine, la nature et la position du motif aryle sur le noyau pyridinique, ainsi que la taille du cycle non-aromatique. La synthèse d’une dernière famille de dérivés bisaryliques a enrichi les études de relation structure-activité, connues dans la littérature, associées à ce type de ligands 5-HT7. La variation du cycle aromatique central (phényle, 1,3-diazine et 1,2,4- triazine) a révélé d’importantes conséquences sur l’affinité des molécules. / Among all the neurotransmitters identified up-to-date, serotonin (5-Hydroxytryptamine, 5-HT) is mediated by the most complex system of receptors. The 5-HT7 receptors are the latest discovered (1993) and have many implications both in the central nervous system and in peripheral tissues. The therapeutic potential of new 5- HT7 ligands, selective over the other GPCRs, motivated our research project. Our studies were focused on the design of three different classes of 5-HT7 ligands. The first class was built on a benzimidazolone scaffold. Various modulations afforded a shift of the affinity profile from the 5-HT1ARs to the 5-HT7Rs. A second class of 3-aminofuro- or pyrano[2,3-b]pyridines are in fact the heteroanalogues of one of the most interesting current 5-HT7 selective agonists: the 3-aminochromans. Their synthesis involved an intramolecular Diels-Alder cycloaddition key step starting from a 1,2,4-triazine judiciously substituted in 3 with a convenient aminoalkynol. The developed methodology afforded the variation of the substituents on the amine moiety, of the aromatic substituent and its position on the pyridinic core and of the non-aromatic ring size. A last class of bisarylic derivatives further explored the SAR tendencies of this type of 5-HT7 ligands by modulating the main aromatic scaffold in the benzene, pyrimidine and 1,2,4-triazine series.

La presenza di pesticidi nelle acque di falda è emersa come un importante problema ambientale negli ultimi decenni. In base a “Rapporto nazionale pesticidi nelle acque - Dati 2015-2016” (ISPRA, 2018), in Italia, gli erbicidi triazinici e i loro metaboliti sono tra le sostanze identificate con più frequenza nelle acque, sebbene l’atrazina sia stata bandita nel 1992 e l’utilizzo di terbutilazina sia sottoposto a severe restrizioni. Lo scopo di questo progetto è valutare e quantificare la presenza di atrazina, terbutilazina e dei loro metaboliti nelle acque di falda in aree maidicole italiane. I risultati dimostrano come le molecole oggetto di studio siano state frequentemente individuate nei campioni di acqua di falda, anche se a concentrazioni inferiori al limite stabilito dalla Commissione Europea. Considerando che l’utilizzo di questi erbicidi è proibito o fortemente regolamentato, è interessante valutare il loro comportamento in una scala temporale pluriennale al fine di mettere in evidenza la contaminazione delle acque di falda dovute all’uso diffuso e alla persistenza ambientale di tali molecole. / The presence of pesticides in groundwater has emerged as an important environmental issue in the last decades. According to “Rapporto nazionale pesticidi nelle acque - Dati 2015-2016” (ISPRA, 2018), in Italy triazine herbicides and their metabolites are among the substances most frequently detected in water. While terbuthylazine is still used under restriction, atrazine was banned in 1992. The aim of research project is to investigate the presence of atrazine, terbuthylazine and their metabolites in groundwater in Italian maize-growing areas in order to supply data and information on the groundwater quality. The results show that atrazine, terbuthylazine and their metabolites were often detected in groundwater, even if their concentrations were below the limit established by European Commission. Considering these molecules are banned or heavily regulated, it is interesting to evaluate their behavior on a multiannual time scale in order to highlight the groundwater contamination due to the widespread use and to the environmental persistence of these substances.

Le cancer constitue l’une des principales causes de mortalité, et représente, de ce fait aujourd’hui un problème de santé publique majeur. Depuis quelques années, les alcaloïdes marins représentent une source d’inspiration importante pour les chimistes en vue d’obtenir de nouveaux médicaments anticancéreux. Dans cette optique, des recherches effectuées au sein de notre laboratoire ont fait état de la synthèse d’analogues de ces alcaloïdes possédant une structure tris aromatique. Nous avons développé des molécules originale analogues de ces alcaloïdes disposant d’un hétérocycle central (1,2,4-triazine et imidazo[1,2-b][1,2,4,5]tétrazine) sur lequel sont greffés deux noyaux phényles diversement substitués. L’obtention de ces composés a également été l’occasion de développer de nouvelles méthodologies de synthèse. Ainsi une nouvelle réaction de type Buchwald-Hartwig sur des méthylsulfanyl-1,2,4-triazines a pu être mise au point ainsi qu’une méthode de CH arylation palladocatalysée sur le noyau imidazo[1,2-b][1,2,4,5]tétrazine. Une partie est aussi consacrée aux réactions multicomposants de type Groebke-Blackburn. Différentes évaluations pharmacologiques ont été réalisées, notamment des tests d’inhibition sur différentes kinases et de cytotoxicité sur diverses lignées cellulaires cancéreuses humaines. / Cancer, one of the leading causes of death, represents today a major public health problem. Over the last few years, marine alkaloids represent a source of inspiration for chemists in order to obtain new anticancer drugs. For this purpose, as a part of our laboratory researches, analogues of marine alkaloids were synthesized possessing a tris-aromatic structure. We developed originals analogs of these alacaloïds formed by a central heterocycle core (1,2,4-triazine et imidazo[1,2-b][1,2,4,5]tetrazine) on wich is graft two arylic moiety variously substituted. Obtaining these compounds was also an opportunity to develop news synthetic methodologies. So a new Buchwald-Hartwig reaction type based on methylsulfanyl-1,2,4-triazines has been perfect, as palladocatalyzed CH arylation pathway on imidazo[1,2-b][1,2,4,5]tetrazine. A part is devoted to Groebke-Blackburn multicomponant reaction. Various pharmacological analyses were carried out in particular with inhibition of various kinases and cytotoxicity evaluation on various human cancer cell lines.

Les travaux réalisés dans le cadre de la thèse avaient pour but la synthèse de nouveaux fluorophores basés sur les unités BODIPYs et hydroxyphényl-s-triazines. Pour être utilisées comme sondes efficaces dans des applications en chimie et en biologie, les chromophores doivent présenter une forte brillance et des rendements quantiques de fluorescence élevés, une modulation aisée de ses propriétés optiques ainsi qu’une bonne stabilité chimique et photochimique. Une stratégie originale et efficace a été développée pour l’obtention de dérivés d’o-hydroxyphényl-s-triazine. Ces derniers présentent des déplacements de Stokes anormalement élevés ayant pour origine un transfert de proton intramoléculaire ultrarapide à l’état excité (ESIPT). L’extension du système π-conjugué sur les différentes plateformes de départ a été réalisée par couplages pallado-catalysés et/ou condensation de Knoevenagel, permettant ainsi d’accéder à une large gamme spectrale en absorption et en émission. Le développement d’une nouvelle voie de synthèse à permis l’obtention d’oligo-BODIPYs par couplage oxydant réalisé en associant PIFA et un acide de Lewis. Toutes les propriétés photophysiques des nouvelles sondes ont été étudiées et ont fait l’objet de discussions détaillées. / The study undertaken in this thesis was the engeneering of new fluorescent dyes based on BODIPY and o-hydroxyphenyl-s-triazine units. The focus has been on the development of dyes displaying large absorption cross sections, emission wavelength tunability, high photostability and fluorescent quantum yields by using original synthetic strategies. As a part of our research program on the design of novel fluorescent dyes exhibiting large Stokes shifts, we developped an efficient method for the synthesis of o-hydroxyphenyl-s-trazine for which an anormalous emission was observed due to an intramolecular proton transfert in the excited state (ESIPT process). The fine tuning of the absorption and emission wavelength for both plateforms were achieved by extension of the π-conjugated system with aryl and alkyl moieties using palladium cross coupling or via a styryl linkage using Knoevenagel condensation. Another strategy to enhance the fluorescence performances consists in the rigidization of the plateforms. Various oligo-BODIPYs have been obtained by an unprecedented oxydative coupling reaction using Phenyliodine(III)bis(trifluoroacetate) (PIFA) in conjunction with a Lewis acid. All compounds spectral characteristics were investigated and their photophysical properties discussed.