A Cubebina (CB) é uma lignana da classe das dibenzilbutirolactonas presente em uma ampla variedade de espécies vegetais espalhadas pelo mundo. Nos últimos anos, vários estudos têm demonstrado seu potencial para o tratamento de doenças como Leishmaniose e Doença de Chagas, além de possuir ação antiinflamatória e analgésica. Entretanto, apesar da CB apresentar diversas potencialidades terapêuticas, sua utilização ainda é limitada devido à sua baixa solubilidade em água, que compromete sua biodisponibilidade. Os dendrímeros são estruturas quase esféricas, de dimensão nanométrica, com grande número de subgrupos funcionais reativos e espaços interiores protegidos. São capazes de complexar com moléculas e, dessa forma, aumentar a solubilidade do fármaco. De forma semelhante, as ciclodextrinas (CDs) são oligossacarídeos cíclicos que possuem a capacidade de interagir com moléculas hidrofóbicas através de sua cavidade que também é hidrofóbica. Isso as torna capazes de aumentar a solubilidade de fármacos pouco solúveis aumentando sua biodisponibilidade. Nesse trabalho foram obtidos complexos dessas macromoléculas com a CB por diferentes métodos. Metodologias de quantificação da CB, nas formas livre e complexada, foram desenvolvidas utilizando técnicas de espectrofotometria e de cromatografia líquida de alta eficiência. Esses sistemas foram caracterizados utilizando técnicas apropriadas como estudos de solubilidade de fase, espectroscopia no IV, difração de raios X, RMN H1 e simulações de modelagem e dinâmica molecular. Os resultados demonstraram que tanto os dendrímeros quanto as ciclodextrinas são capazes de gerar complexos solúveis com a CB sendo os melhores resultados obtidos com a HP--CD. Os resultados desse trabalho permitiram concluir que tanto dendrímeros quanto CDs são estruturas adequadas e promissoras para a veiculação da CB, aumentando assim o seu potencial para aplicações biológicas, visando o tratamento de diversas patologias. / Cubebin (CB) is a lignan from the class of dibenzylbutyrolactones present in a wide variety of plant species around the world. Its known for its anti-inflammatory and analgesic effects. In recent years, several studies have demonstrated its potential to treat diseases such as leishmaniasis and Chagas. Although the CB shows several potential therapeutics, its use is still limited due to its low water solubility which compromises its bioavailability. The dendrimers are nearly spherical structures, nanometer-sized, with large number of reactive functional groups and protected inner. They are capable of complexing with molecules and thereby increase the solubility of the drug. Similarly, cyclodextrins (CDs) are cyclic oligosaccharides that have the ability to interact with hydrophobic molecules through the cavity which is also hydrophobic. This makes them capable of increasing the solubility of poorly soluble drugs by increasing their bioavailability. In this work, complexes of macromolecules with CB were obtained by different processes. Methodologies for quantification of free and complexed CB were developed by spectrophotometry and high performance liquid chromatography. Moreover, these systems were characterized by techniques such Phase Solubility Studies, IR spectroscopy, X-ray diffraction, NMRH1, modeling and molecular dynamics simulation. The results showed that both dendrimers and cyclodextrins are capable to form soluble complexes with CB. Best results were obtained with HP--CD. The findings of this study indicate that both dendrimers and CDs are appropriated structures to release the CB and also increase its potential for biological applications, focusing on the treatment of various diseases.

D.Phil. (Chemistry) / The application of dendritic-based materials has attracted great interest. For the first time this research has investigated the feasibility of poly (propyleneimine) (PPI) dendrimers and hyperbranched polyethyleneimine (HPEI) in combination with beta-cyclodextrin (β-CD) embedded in polysulfone (PSf) membrane for water treatment. The advantage of embedding these conjugates (β-CD-PPI and β-CD-HPEI) in PSf membranes is the presence of numerous nanocavities which can act as water channels allowing easy water passage through the membrane improving water permeability. Secondly, the presence of functional groups such as –OH and –NH greatly improves hydrophilicity of membranes. Commercial polysulfone (PSf) ultrafiltration membranes were crosslinked with β-cyclodextrin-poly (propyleneimine) (β-CD-PPI) and β-cyclodextrin-hyperbranched polyethyleneimine (β-CD-HPEI) using trimesoyl chloride (TMC) by interfacial polymerisation. These membranes were used in the rejection of Aldrich humic acid (molecular weight: 4.1 kDa) from synthetic water samples prepared in the laboratory. Moreover, β-cyclodextrin-poly (propyleneimine) (β-CD-PPI) was used as a host for the preparation of Fe/Ni nanoparticles. The new membranes were synthesised by crosslinking β-CD-PPI with trimesoyl chloride and subsequently loading Fe/Ni nanoparticles and this was supported on a commercial polysulphone (PSf) layer for the degradation of 2,4,6-trichlorophenol (2,4,6-TCP). The membrane surfaces were characterised using Fourier transform infrared/attenuated total reflectance (FT-IR/ATR) spectroscopy , scanning electron microscopy (SEM), atomic force microscopy (AFM), high resolution transmission electron microscopy (HR-TEM), water-contact angle, and water-intake capacity...

Depuis plusieurs années, notre équipe de recherche s'intéresse au développement de nouvelles familles de dendrimères utilisant des dérivés bio sourcés (pentoses, glycérol ou dérivés correspondants) dont la valorisation est un sujet de recherche d'intérêt de notre région. Ainsi, certains glyco- ou glycérodendrimères dérivés de PPIs (polypropylène imines) ont déjà été obtenus et valorisés dans plusieurs domaines. Cette thèse présente la synthèse et la caractérisation de nouveaux dendrimères dérivés du glycérol. Leur efficacité dans des processus catalytiques et d'encapsulation de molécules d'intérêt a également été démontrée.Dans un premier temps, deux nouvelles familles de dendrimères directement constitués de glycérol en tant que brique élémentaire ont été synthétisées : l'une via des réactions de « click chemistry » pour obtenir des glycéroclickdendrimères, et l'autre via des réactions successives d'allylation et d'oxydation pour obtenir des glycéroladendrimères.Dans un second temps, la fonctionnalisation de dendrimères PAMAMs par du carbonate de glycérol a été effectuée par synthèse « classique » ou assistée par micro-ondes. L'efficacité de ces glycérodendrimères ainsi obtenus (en comparaison avec des glycérodendrimères dérivés de PPIs) a été évaluée : tout d'abord, pour la stabilisation de nanoparticules de platine utilisées en catalyse d'hydrogénation de cétones α,β-insaturées en milieu aqueux, puis, pour l'encapsulation de molécules organiques d'intérêt. Pour finir, une première approche de dynamique moléculaire a été réalisée afin de déterminer les propriétés structurales de deux glycérodendrimères issus de la réaction de couplage entre le carbonate de glycérol et un PAMAM ou un PPI. / Since a few years, our team is interested in developing dendrimers using different biosourced derivatives (pentoses, glycerol or derivatives) whose valuation is a prime research topic within our region. Some glyco- or glycerodendrimers derivate from PPIs (polypropylenimines) were already obtained and valued in several domains. This thesis presents the synthesis and the characterization of new glycerol-based dendrimers. Their efficiency in catalytic processes or for the encapsulation of molecules of interest was also demonstrated. First, two new families of dendrimers directly constituted of glycerol as building block, were synthesized: one via click chemistry reactions to obtain glyceroclickdendrimers, and the other, via successive reactions of allylation and oxidation to obtain glyceroladendrimers. Secondly, the functionalization of PAMAM's dendrimers with glycerol carbonate was carried out either by “classical” or microwave assisted synthesis. The efficiency of these glycerodendrimers (in comparison with PPI-based glycerodendrimers) was evaluated: firstly, for the stabilization of platinum nanoparticles used for the catalysis of hydrogenation of α,β-unsaturated ketones in aqueous media, and then, for the encapsulation of organic molecules of interest. Finally, a first molecular dynamics approach was realized to determine the structural properties of two glycerodendrimers from the coupling reaction between the glycerol carbonate and PAMAM or PPI.

Les dendrimères et polymères contenant des métaux de transition comme le fer, lecobalt et le rhodium peuvent servir à la fabrication des nanomatériaux utiles à lacatalyse, la reconnaissance moléculaire et l’électronique moléculaire. Pour leurconstruction, des liaisons ioniques, de la chimie click : CuAAC et hydroamination, lapolymérisation ROMP et la polymérisation radicalaire ont été utilisés et ont permis laformation de nouveaux types de polyélectrolytes metallocéniques. La synthèse denouvelles nanoparticules d’or, d’argent et de palladium à partir de cesmétallopolymères et métallodendrimères ont été mises au point, conduisant à desréseaux à architecture spécifique bien définie. Ces assemblages supramoléculaireset ingénierie moléculaire ouvrent la voie vers l’application de la chimieorganométallique dans la conception de nouveaux nanomatériaux nanoparticulairesstructurés à l’aide des propriétés rédox des métallomacromolécules. / Dendrimers and polymers containing transition metals such as iron, cobalt andrhodium can serve in the fabrication of useful nanomaterials for catalysis, molecularrecognition and molecular electronics. For their construction, ionic bonds, clickchemistry: CuAAC and hydroamination, ROMP and radical polymerization were usedand allowed the formation of new types of metallocenyl polyélectrolytes. Thesynthesis of new gold, silver and palladium nanoparticles from these metallopolymersand metallodendrimers has been developed, leading to specific and well-definedarchitectures. These supramolecular assemblies and molecular engineering opensthe way towards the application of organometallic chemistry in the design of newstructured nanoparticle-containing nanomaterials using the redox properties ofmetallomacromolecules.

No description available.

Flat dendrimers, consisting of a hexavalent aromatic core and rigid ethynyl units locked in place by ether connections were developed based upon the divergent synthetic method. Alternating functional groups were adopted on each site of the hexa-substituted benzene, in order to avoid undesired cyclization pathways. The flat structures of conjugated dendrimers would allow investigation on the discotic liquid crystal properties. In addition, these ethylnyl dendrimers are expected to show directed energy and electron transfer with a highly conjugated system, and thus are effective in the preparation of photoreactive materials such as electronic sensors or light harvesting materials. Conjugated polycyclic aromatic hydrocarbons, consisting of naphthalene, anthracene, pyrene, and phenanthrene groups connected via 1,3,5-triethynylbenzene cores, were synthesized. These molecules exhibited luminescence properties and the π-complexation with a mercury trifunctional lewis acid are expected to enhance the phosphorescence in the presence of the heavy metal due to the spin-orbit coupling. Besides, owing to the presence of heavy metal atom in the Au (I) complexes linked by s-bonded triethynyltriphenylene luminophore, the phosphorescence occurs from a metal-centered emission. The conjugated organic luminophores have been developed to produce excellent quantum efficiencies, brightness, and long lifetimes.

The objectives of this research were to identify the individual ionization constants (pKa values) of lipopeptide (daptomycin), evaluate the factors of pH, concentration, temperature, and calcium ions on daptomycin aggregation in aqueous solutions, and elucidate the effects of conformation and aggregation on ionization and the interaction mechanism between polyamidoamine (PAMAM) dendrimers and daptomycin. Daptomycin is a cyclic anionic lipopeptide antibiotic. It is composed of 13 amino acids with six ionizable groups, four side-chain carboxylic acids and two side-chain amine residues. The pKa values for individual daptomycin residues have not been elucidated. The sequence-specific pKa values for the four acidic residues and one aromatic amine (Kyn-13) in daptomycin were determined in the monomeric state by TOCSY 2D 1H NMR. From the NMR pH titration, the estimated pKa values for Asp-3, Asp-9, and mGlu-12 were determined to be 4.15, 3.85, and 4.55 in the absence of salt, and 4.07, 3.83, and 4.39 in the presence of 150 mM NaCl, respectively. The pKa value for Asp-7 is estimated to be ~1.01 in the absence of salt and 1.31 in the presence of salt. The estimated Hill coefficients for Asp-7 were 0.72 and 1.31 in the absence and presence of salt, respectively. The increase in Hill coefficients from 0.72 to 1.31 with increasing salt concentration is consistent with the estimated lower pKa in the absence of salt and suggests that a salt bridge is formed in solution possibly between Asp-7 acidic group and the neighboring Orn-6 basic group. The pKa value of the aromatic amine (Kyn-13) was confirmed using UV and fluorescence spectroscopic titrations. Aggregation behavior and critical aggregation concentration (CAC) values of daptomycin were evaluated in the different pH aqueous solutions by using the complementary analytical techniques, fluorescence, dynamic and static light scattering, and NMR spectroscopy. Based on fluorescence resonance energy transfer (FRET) from donor Trp-1 to acceptor Kyn-13, the CAC values were determined by an upward inflection of the intrinsic fluorescence emission from Kyn-13 at 460 nm as a function of increasing daptomycin concentration. The pH-dependent CAC values were determined to be 0.14 mM at pH 3.0, 0.12 mM 4.0, and 0.20 mM at pH 2.5 and 5.0. The CAC values obtained by fluorescence spectroscopy were confirmed by dynamic light scattering and NMR spectroscopy. The effects of temperature and calcium ion on daptomycin aggregation were also discussed. The interaction mechanism between daptomycin and PAMAM dendrimers generation 5 and 6 was studied using fluorescence spectroscopy. The shapes of binding isotherms daptomycin were quantitatively described by one- and two-site binding models to estimate binding capacity and dissociation constants. Both solvent pH values and PAMAM generation size were shown to affect the binding model and parameters. The interaction between daptomycin and PAMAM dendrimer was proposed wherein the ionized Asp-3 and Asp-9 residues of daptomycin interact with PAMAM cationic surface amine.

With their three-dimensional macromolecular structure and shape, and with their tuneable properties in both the inner and outer spheres, dendrimers are ideal model compounds in the nanometre range between 1 and 10 nm. The possibility to combine different properties within one macromolecule destines them for use in various high-end research fields such as medicine, pharmacy, biology, supramolecular chemistry, nanotechnology and material sciences. On the basis of their high end-group density and a compact, highly branched molecular structure, dendrimers are successfully investigated as carrier systems for active substances and metal ions (e.g. contrast agents for the visualisation of blood vessels), as templates for metal nanoparticles, as artificial enzymes with defined functions, and as materials for catalysis. / Dendrimere sind aufgrund ihrer dreidimensionalen Makromolekülstruktur und -form und ihrer steuerbaren Eigenschaften sowohl an der Oberfläche als auch im Molekülinneren ideale Modellverbindungen im Nanometerbereich – sie sind zwischen 1 und 10 nm groß –, die vorzugsweise in der Medizin, Pharmazie, Biologie, Supramolekularen Chemie, Nanotechnologie und den Materialwissenschaften eingesetzt werden. Aufgrund ihrer hohen Endgruppendichte und der kompakten, stark verzweigten Molekülform werden Dendrimere unter anderem als Trägermaterialien und Transportsysteme für Wirkstoffe und Metallionen, zum Beispiel als Kontrastmittel zur Visualisierung von Organen und Blutgefäßen, als Template für metallische Nanopartikel, zur Erzeugung künstlicher Enzymfunktionen und in der Katalyse erfolgreich untersucht.

No description available.

No description available.