No description available.

No description available.

De nouveaux synthons bio-sourcés de structure et de fonctionnalité contrôlées ont été préparés à partir de l’oléate de méthyle issu de l’huile de tournesol. Les synthons de type C18-R-C18 et de nature diol et biscarbonate ont ensuite été utilisés pour la synthèse de polyuréthanes thermoplastiques. Selon la nature de R (aliphatique ou aromatique), les propriétés thermomécaniques et rhéologiques de ces polyuréthanes on été ajustées. Dans le cas où R est hydrophile, les synthons de types diols présentent des propriétés amphiphiles permettant la préparation de polyuréthanes en dispersion aqueuse. Pour s’affranchir del’utilisation d’isocyanates, des polyuréthanes ont été préparés par réaction de diamines avec les synthons biscarbonates. Ces derniers ont été synthétisés par réaction de leurs homologues époxydés avec le CO2. / Abstract

The synthesis or the interaction between two or more molecules is known as supramolecular chemistry. The concept of supramolecular chemistry can be applied to the design of new pharmaceutical materials affording new compositions of matter with desirable composition, structure and properties. The design of a two-molecule, or binary, compound using complementary molecules represents an example of an application of crystal engineering. Crystal engineering is the understanding of intermolecular interactions, in the context of crystal packing, in the design of new solid materials. By identifying reliable connectors through molecular recognition or self-assembly, one can build predictable architectures. The study of supramolecular synthesis was accomplished using known pharmaceutical molecules such as Nifedipine (calcium channel blocker used for cardiovascular diseases) and Phenytoin (used as an anticonvulsant drug) and model compounds containing synthons common in pharmaceutical drugs (Crown ethers and Trimesic acid with ether linkages and carboxylic acid dimers, respectively) with complementary molecular additives. The co-crystals formed were characterized by various techniques (IR, m.p., XPD, single X-ray diffraction) and preliminary results were found to exhibit characteristics different from the parent compounds as a direct result of hydrogen bonding and self-assembly interactions. These crystalline assemblies could afford improved solubility, dissolution rate, stability and bioavailability.

Title from PDF of title page. / Document formatted into pages; contains 80 pages. / Thesis (M.S.)--University of South Florida, 2003. / Includes bibliographical references. / Text (Electronic thesis) in PDF format. / ABSTRACT: The synthesis or the interaction between two or more molecules is known as supramolecular chemistry. The concept of supramolecular chemistry can be applied to the design of new pharmaceutical materials affording new compositions of matter with desirable composition, structure and properties. The design of a two-molecule, or binary, compound using complementary molecules represents an example of an application of crystal engineering. Crystal engineering is the understanding of intermolecular interactions, in the context of crystal packing, in the design of new solid materials. By identifying reliable connectors through molecular recognition or self-assembly, one can build predictable architectures. / ABSTRACT: The study of supramolecular synthesis was accomplished using known pharmaceutical molecules such as Nifedipine (calcium channel blocker used for cardiovascular diseases) and Phenytoin (used as an anticonvulsant drug) and model compounds containing synthons common in pharmaceutical drugs (Crown ethers and Trimesic acid with ether linkages and carboxylic acid dimers, respectively) with complementary molecular additives. The co-crystals formed were characterized by various techniques (IR, m.p., XPD, single X-ray diffraction) and preliminary results were found to exhibit characteristics different from the parent compounds as a direct result of hydrogen bonding and self-assembly interactions. These crystalline assemblies could afford improved solubility, dissolution rate, stability and bioavailability. / System requirements: World Wide Web browser and PDF reader. / Mode of access: World Wide Web.

-- / --

Les sécoiridoïdes sont des monoterpènes hautement fonctionnalisés utilisés comme matières premières chirales renouvelables en hémisynthèse, lorsqu’ils sont abondants au sein des végétaux. Un nouveau procédé vert d’extraction aqueuse et de purification utilisant des résines et la chromatographie de partage centrifuge a permis l’isolement de plus de 100 g d’oleuropéine des feuilles d’Olea europaea et d’une douzaine de grammes de sécologanoside et de sweroside des feuilles de Lonicera tatarica. L’ouverture de la lactone du perpivaloylsweroside a été effectuée en milieu organique apolaire par le TMSONa. Cette réaction a été étendue à 8 lactones commerciales et 5 lactones de sécoiridoïdes. Une approche mécanistique de cette nouvelle réaction a été établie sur la γ-butyrolactone à l’aide d’une étude cinétique. Cette réaction a été utilisée pour la conversion du sweroside en sécologanoside en quatre étapes. Cette approche séquentielle a été appliquée avec succès sur les dérivés du sweroside. Quatre nouveaux analogues du sécologanoside et 9 synthons chiraux originaux ont ainsi été isolés. De plus l’étude de la réactivité de l’oleuropéine a permis l’obtention de 4 nouveaux synthons et un analogue isomérique du sécologanoside. Ces analogues de sécologanoside sont précurseurs de nouveaux alcaloïdes indolo-monoterpèniques. Enfin la double liaison exocyclique du sweroside a pu être sélectivement ozonolysée et épimérisée pour conduire à la formation d’un synthon clé pour la synthèse de diterpènes cytotoxiques marins de types xénicanes. / Secoiridoids are highly functionalized monoterpenes and can be used as renewable raw materials in semi-synthesis when they are abundant in plants. A new green process of water extraction and purification by resins or centrifugal partition chromatography allowed the isolation of more than 100 g of oleuropein from Olea europaea leaves and a dozen of grams of secologanin and sweroside from Lonicera tatarica leaves.The lactone ring opening of perpivaloylsweroside was achieved in apolar solvents by TMSONa. The scope of this reaction was extended to 8 commercial lactones and 5 secoiridoid lactones. A mechanistic approach of this new reaction on γ-butyrolactone was established by kinetic studies. This reaction was used for the conversion of perpivaloylsweroside into secologanin, in four steps. This approach was successfully applied on sweroside derivatives. Four enantiopure secologanin analogs and 9 chiral synthons were isolated. Furthermore the reactivity study of oleuropein afforded 3 new synthons and one isomeric analog of secologanin. These secologanin analogs are synthetic precursors of new indolo-monoterpenic alkaloids. Finally the exocyclic double bond of sweroside was selectively ozonolyzed and epimerized to yield a key synthon for the synthesis of cytotoxic marine diterpenes xenicans.

Les lignines ne sont pas suffisamment considérées dans les procédés de bioraffinerie. Pourtant, elles sont une source abondante de synthons aromatiques, et éléments essentiels de la rentabilité de transformation des lignocelluloses. A ce jour, les perspectives de production de synthons à partir des lignines se heurtent aux réactions de condensations des lignines, limitant leurs conversions en produits de faibles masses. Cette étude nous a permis de cerner les conditions propices à l’hydrolyse et/ou aux condensations grâce à l’étude de différentes lignines modèles soumises aux conditions d’acidolyse. D’une part, les conditions propices à l’hydrolyse des liaisons -O-4 sont l’utilisation d’une catalyse homogène (HCl), pour des températures comprises entre 120 et 140°C et une acidité de l’ordre de 0.05 M. A l’inverse, l’emploi d’une catalyse hétérogène (Montmorillonite K10) est peu efficace car elle doit s’affranchir des phénomènes d’adsorption du substrat tout en lui permettant d’accéder à ses sites actifs. D’autre part, les réactions de condensation secondaires sont exacerbées par l’emploi de l’argile de Montmorillonite, mais aussi par l’augmentation de l’acidité et de la température, elles mêmes nécessaires pour une bonne hydrolyse. La substitution de l’alcool coniférylique par le coniféraldéhyde permet de minimiser ces condensations secondaires du fait de sa forte stabilité dans les conditions d’acidolyse. Toutefois, l’incorporation de ce type de précurseur dans les lignines provoque une diminution de la fréquence des liaisons -O-4. Cette réduction du potentiel d’hydrolyse des lignines est compensée par l’exacerbation des réactions de rétroaldolisation. Pour les condensations primaires, l’acidolyse des lignines pures -O-4 nous permet d’affirmer que celles-ci, constantes face à l’augmentation de la concentration en acide et en nucléophiles aromatiques, seraient plutôt de type intramoléculaire. / Lignins are not sufficiently considered in the biorefinery processes. However, they are a rich source of aromatic building blocks, and essential elements of lignocellulose processing viability. Although the production prospects of building blocks from lignins exist, their strong affinities for condensation reactions limit the conversion into low molecular weight products. This study allowed us to identify hydrolysis or condensation suitable conditions by studying different models lignins subjected to acidolysis conditions. On the one hand, suitable conditions for the -O-4 bonds hydrolysis are the use of homogeneous catalysis (HCl), for temperatures and HCl concentration ranged from 120 to 140 ° C and from 0.05 M to 0.1M. In contrast, the use of heterogeneous catalysis (Montmorillonite K10) is inefficient because it has to overcome the substrate adsorption and allow an access to its active sites. On the other hand, secondary condensation reactions are exacerbated by the use of Montmorillonite clay, but also by acidity and temperature increases, themselves necessary for an efficient hydrolysis.The substitution of coniferyl alcohol by coniferaldehyde minimizes these condensation reactions due to its high stability in acid conditions. However, the incorporation of this precursor in lignin leads to a decrease of -O-4 bond frequency. This reduction of lignin hydrolysis potential is compensated for the exacerbation of retroaldolisation reactions. About primary condensations, pure -O-4 lignins acidolysis allows us to claim that this kind of reactions, unchanged at the hand of acid or aromatic nuclei concentration increase, are intramolecular.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study shows the triazenes ligands and complexes Pd(II), K+ and Au(I) obtained from reactions of the ligands with fragments para-sulfonamidephenyl, comprising triazene ligand 1,3-bis (4 - sulfonamidephenyl) (1) and the complex {trans-Bis[1,3-bis(4-sulfonamidephenyl)triazenide-κN1]bis(pyridine-κN)palladium(II)}{tetra(pyridine-κN)palladium(II)}bis(potssium)·water (2) and for compounds containing orto-halophenyl fragments represented by [1,3-bis(2-fluorophenyl)triazenide-κN1](triphenylphosphine- κP)gold(I) (3), [1,3-bis(2-chlorinephenyl)triazenide-κN1](triphenylphosphine-κP)gold(I) (4), [1,3-bis(2-bromidephenyl)triazenide-κN1](triphenylphosphine-κP)gold(I) (5) and [1,3-bis(2-iodinephenyl)triazenide-κN1](triphenylphosphine - κP)gold(I) (6) complexes. The compounds reported were characterized by X-ray diffraction on single crystal, and their structures in solid state are formed through supramolecular arrangements via classical and non-classical hydrogen bonding, as in the case of the compounds with the sulfonamide grouping, one can observe the formation of supramolecular synthons. In complexes 4, 5 and 6 it is observed to occur interactions halogen···halogen characterized by the formation of dimeric units associated by a center of inversion, besides having geometries classified by the angle of the links formed between the halogen and carbon atoms. Compounds 1, 2, 3, 4, 5 and 6 were subjected to evaluation front of biological activity, such as plasmidial DNA cleavage studies, evaluation of cytotoxicity and antibacterial activity, showing promising results. / Este trabalho apresenta o estudo de ligantes triazenos e complexos de Pd(II), K+ e Au(I) obtidos a partir de reações com os ligantes com fragmentos para-sulfonamidafenila compreendendo o ligante 1,3-bis-(4-sulfonamidafenil)triazeno (1) e o complexo {trans-Bis[1,3-bis(4-sulfonamidafenil)triazenido-κN1]bis(piridina-κN)paládio(II)}{tetra(piridina-κN)paládio(II)}bis(potássio)·água (2) e para compostos contendo fragmentos orto-halofenila representados pelos complexos [1,3-bis(2-fluorofenil)triazenido-κN1](trifenilfosfina- κP)ouro(I) (3), [1,3-bis(2-clorofenil)triazenido-κN1](trifenilfosfina- κP)ouro(I) (4), [1,3-bis(2-bromofenil)triazenido-κN1](trifenilfosfina- κP)ouro(I) (5) e [1,3-bis(2-iodofenil)triazenido-κ-N1](trifenilfosfina- κP)ouro(I) (6). Os compostos relatados foram caracterizados por difração de raios X em monocristal, e suas estruturas no estado sólido são formadas através de arranjos supramoleculares via ligações de hidrogênio clássicas e não clássicas, como no caso dos compostos com o grupamento sulfonamida, pode-se observar a formação de synthons supramoleculares. Nos complexos 4, 5 e 6 é observada a ocorrência de interações halogênio···halogênio caracterizadas pela formação de unidades díméricas associadas por um centro de inversão, além de apresentarem geometrias classificadas pelo ângulo de ligações formado entre os átomos de halogênio e carbono. Os compostos 1, 2, 3, 4, 5 e 6 foram submetidos a avaliação frente a atividade biológica, como estudos na clivagem do DNA plasmidial, avaliação da citotoxicidade e atividade antibacteriana, mostrando resultados promissores.

This dissertation endeavors to delineate practical paradigms for crystal engineering based upon the understanding of supramolecular chemistry and self-assembly, i.e. the design and synthesis of novel functional crystalline materials. Two basic metal-organic building units, Zn(RCO2)2(py)2 and (L2)M2(RCO2)4 (M = Zn, Cu), as well as nano-scaled secondary building units (nSBUs) that are constructed from Cu2(RCO2)4 are researched and discussed. Design strategies have been developed to propagate these metal-organic synthons into predictable coordination polymer networks. A series of crystal structures, as well as their syntheses and characterization, are presented. This work demonstrates that supramolecular structures can be designed from pre-selected molecular precursors with the consideration of chemical functionalities and geometrical arrangements. The design strategy represents a practical paradigm for the construction of porous materials as well as interesting networks with special topologies. The modular nature of these metal-organic building units introduces a broad impact on the discovery of novel coordination compounds with potential useful properties.