Conception, synthèse et études structurales de foldamères aromatiques repliés en feuillet

Ce travail a pour objectif d augmenter la diversité des foldamères par le développement d une nouvelle classe d architectures abiotiques mimant le repliement des feuillets b protéiques. La stratégie employée repose sur des processus de structuration qui diffèrent de ceux observés au sein du vivant. Les deux éléments essentiels des systèmes naturels, à savoir la boucle courte et flexible d acides aminés et les brins b liés entre eux par des liaisons hydrogènes, sont ici substitués respectivement par un coude rigide formé de noyaux aromatiques et par des oligoarylamides plans interagissant par empilement aromatique.Ces objets ont été conçus pour adopter des structures repliées caractérisables en solution par spectroscopie RMN et à l état solide par diffraction des rayons X. Dans une première partie, l optimisation du pseudo-coude b et de la séquence des brins, ainsi que l exploration des premières architectures en feuillet seront étudiées à travers la conception, la synthèse et les études structurales de ces oligoamides et oligoamines aromatiques. Dans une seconde partie, le concept mis en oeuvre sera étendu à la synthèse de foldamères plus élaborés à brins courbés, ouvrant ainsi des perspectives intéressantes vers l obtention d architectures toujours plus complexes.The purpose of this work is to expand foldamer diversity by developing a novel class of abiotic b-sheet-like architectures. Our strategy uses inter-strand p-p aromatic stacking between sequences of aromatic oligoamides and oligoamines to mimic the natural stabilization of b-strands, which occurs through a network of regularly spaced hydrogen bonds. These oligamide and oligoamine sequences are connected by a rigid U-shaped moiety that creates a turn and initiates strand formation.These molecules have been designed to adopt compact folded structures that can be studied in solution by NMR spectroscopy and in the solid state by X-ray crystallography. In the first part of this dissertation, we report our stepwise approach in the development of b-sheet-like aromatic amide-based foldamers: from the optimization of the design elements and the use of macrocycles, to the synthesis of multi-turn structures. In the second part, the concept will be extented to the synthesis of more elaborate curving strand b-sheet-like foldamers, opening up new perspectives for more complex architectures.BORDEAUX1-Bib.electronique (335229901) / SudocSudocFranceF

Bureaucracy and the challenges of coordination in service delivery : a comparative study of Kabulonga and Kamanga primary schools in Lusaka City, 2010- 2014

Masters in Public Administration - MPAThe study Bureaucracy and the challenges of coordination in service delivery: A comparative study of Kamanga and Kabulonga Primary Schools in Lusaka City 2010- 2014 had the main aim of finding out the challenges encountered in the coordination of primary education within Lusaka City. The study was attempting to draw lessons and understand why schools within the same district and level (primary) were performing differently. There are many reasons as to why the study is important. To begin with, the information derived from this study is important in the post MDG implementation period after the end of the implementation period in 2015. Second, no research has been done on organizational design and development in the context of Africa and Zambia. While some scholars have published on education management, the aspect of bureaucratic coordination has not been adequately addressed. The study took a comparative approach to research. Qualitative research was deployed as means of carrying out the study. Both primary and secondary data were used. Primary data was collected from two schools which were sampled purposively. The researcher approached the District education office to recommend two schools (one performing well and another underperforming one). The two schools recommended are Kabulonga Primary and Kamanga Primary respectively. A sample of seven experts was then extracted including two teachers from each school, a school manager for each school and the district planning officer at district level. Data was collected using semi structured interview guides between December 2015 and January 2016. Data was collected through a recorder, transcribed and analyzed using thematic analysis. On the other hand, secondary data was obtained from policy, legal, government and internal documents. Among the major findings was that the school's locations or environments have a major impact on how they function. For instance Kabulonga performed better than Kamanga because the latter is in an area where majority are low earning poor households. Further, internally, the ability of Kabulonga to plan in a long term manner enabled the school to match resources with specific priorities, something Kamanga did not do. Furthermore, the avenues used for communication in the district have got poor information feedback mechanisms. The study thus recommended that the government should distribute resources to schools with a connotation of giving an extra financial bell out to those schools operating in poverty stricken areas since such schools cannot find other means of survival

Design, synthesis and structural studies of ß-sheet-like aromatic amide-based foldamers

Ce travail a pour objectif d’augmenter la diversité des foldamères par le développement d’une nouvelle classe d’architectures abiotiques mimant le repliement des feuillets β protéiques. La stratégie employée repose sur des processus de structuration qui diffèrent de ceux observés au sein du vivant. Les deux éléments essentiels des systèmes naturels, à savoir la boucle courte et flexible d’acides aminés et les brins β liés entre eux par des liaisons hydrogènes, sont ici substitués respectivement par un coude rigide formé de noyaux aromatiques et par des oligoarylamides plans interagissant par empilement aromatique.Ces objets ont été conçus pour adopter des structures repliées caractérisables en solution par spectroscopie RMN et à l’état solide par diffraction des rayons X. Dans une première partie, l’optimisation du pseudo-coude β et de la séquence des brins, ainsi que l’exploration des premières architectures en feuillet seront étudiées à travers la conception, la synthèse et les études structurales de ces oligoamides et oligoamines aromatiques. Dans une seconde partie, le concept mis en oeuvre sera étendu à la synthèse de foldamères plus élaborés à brins courbés, ouvrant ainsi des perspectives intéressantes vers l’obtention d’architectures toujours plus complexes.The purpose of this work is to expand foldamer diversity by developing a novel class of abiotic β-sheet-like architectures. Our strategy uses inter-strand π-π aromatic stacking between sequences of aromatic oligoamides and oligoamines to mimic the natural stabilization of β-strands, which occurs through a network of regularly spaced hydrogen bonds. These oligamide and oligoamine sequences are connected by a rigid U-shaped moiety that creates a turn and initiates strand formation.These molecules have been designed to adopt compact folded structures that can be studied in solution by NMR spectroscopy and in the solid state by X-ray crystallography. In the first part of this dissertation, we report our stepwise approach in the development of β-sheet-like aromatic amide-based foldamers: from the optimization of the design elements and the use of macrocycles, to the synthesis of multi-turn structures. In the second part, the concept will be extented to the synthesis of more elaborate curving strand β-sheet-like foldamers, opening up new perspectives for more complex architectures

Design, synthesis and structural studies of ß-sheet-like aromatic amide-based foldamers

Ce travail a pour objectif d’augmenter la diversité des foldamères par le développement d’une nouvelle classe d’architectures abiotiques mimant le repliement des feuillets β protéiques. La stratégie employée repose sur des processus de structuration qui diffèrent de ceux observés au sein du vivant. Les deux éléments essentiels des systèmes naturels, à savoir la boucle courte et flexible d’acides aminés et les brins β liés entre eux par des liaisons hydrogènes, sont ici substitués respectivement par un coude rigide formé de noyaux aromatiques et par des oligoarylamides plans interagissant par empilement aromatique.Ces objets ont été conçus pour adopter des structures repliées caractérisables en solution par spectroscopie RMN et à l’état solide par diffraction des rayons X. Dans une première partie, l’optimisation du pseudo-coude β et de la séquence des brins, ainsi que l’exploration des premières architectures en feuillet seront étudiées à travers la conception, la synthèse et les études structurales de ces oligoamides et oligoamines aromatiques. Dans une seconde partie, le concept mis en oeuvre sera étendu à la synthèse de foldamères plus élaborés à brins courbés, ouvrant ainsi des perspectives intéressantes vers l’obtention d’architectures toujours plus complexes.The purpose of this work is to expand foldamer diversity by developing a novel class of abiotic β-sheet-like architectures. Our strategy uses inter-strand π-π aromatic stacking between sequences of aromatic oligoamides and oligoamines to mimic the natural stabilization of β-strands, which occurs through a network of regularly spaced hydrogen bonds. These oligamide and oligoamine sequences are connected by a rigid U-shaped moiety that creates a turn and initiates strand formation.These molecules have been designed to adopt compact folded structures that can be studied in solution by NMR spectroscopy and in the solid state by X-ray crystallography. In the first part of this dissertation, we report our stepwise approach in the development of β-sheet-like aromatic amide-based foldamers: from the optimization of the design elements and the use of macrocycles, to the synthesis of multi-turn structures. In the second part, the concept will be extented to the synthesis of more elaborate curving strand β-sheet-like foldamers, opening up new perspectives for more complex architectures

Conception, synthèse et études structurales de foldamères aromatiques repliés en feuillet

The purpose of this work is to expand foldamer diversity by developing a novel class of abiotic β-sheet-like architectures. Our strategy uses inter-strand π-π aromatic stacking between sequences of aromatic oligoamides and oligoamines to mimic the natural stabilization of β-strands, which occurs through a network of regularly spaced hydrogen bonds. These oligamide and oligoamine sequences are connected by a rigid U-shaped moiety that creates a turn and initiates strand formation.These molecules have been designed to adopt compact folded structures that can be studied in solution by NMR spectroscopy and in the solid state by X-ray crystallography. In the first part of this dissertation, we report our stepwise approach in the development of β-sheet-like aromatic amide-based foldamers: from the optimization of the design elements and the use of macrocycles, to the synthesis of multi-turn structures. In the second part, the concept will be extented to the synthesis of more elaborate curving strand β-sheet-like foldamers, opening up new perspectives for more complex architectures.Ce travail a pour objectif d’augmenter la diversité des foldamères par le développement d’une nouvelle classe d’architectures abiotiques mimant le repliement des feuillets β protéiques. La stratégie employée repose sur des processus de structuration qui diffèrent de ceux observés au sein du vivant. Les deux éléments essentiels des systèmes naturels, à savoir la boucle courte et flexible d’acides aminés et les brins β liés entre eux par des liaisons hydrogènes, sont ici substitués respectivement par un coude rigide formé de noyaux aromatiques et par des oligoarylamides plans interagissant par empilement aromatique.Ces objets ont été conçus pour adopter des structures repliées caractérisables en solution par spectroscopie RMN et à l’état solide par diffraction des rayons X. Dans une première partie, l’optimisation du pseudo-coude β et de la séquence des brins, ainsi que l’exploration des premières architectures en feuillet seront étudiées à travers la conception, la synthèse et les études structurales de ces oligoamides et oligoamines aromatiques. Dans une seconde partie, le concept mis en oeuvre sera étendu à la synthèse de foldamères plus élaborés à brins courbés, ouvrant ainsi des perspectives intéressantes vers l’obtention d’architectures toujours plus complexes

Conception et synthèse de nouveaux ligands des récepteurs alpha7 nicotiniques de structure pyridinique

CAEN-BU Médecine pharmacie (141182102) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

Aromatic Oligoamide beta-Sheet Foldamers

International audienceA rational approach for the construction of multistranded artificial beta-sheets based not on hydrogen bonding, but on pi-pi aromatic stacking is presented. Using 4,6-dinitro,3,5-phenylenediamine units, rigid turns were designed that allow face-to-face pi-pi interactions between appended linear aromatic segments to be strong enough for folding in an organic solvent, but weak enough to prevent aggregation and precipitation. Solution and solid state studies on a series of turn units showed that the desired degree of rigidity, resulting from hindered bond rotation, could be fine tuned by the inclusion of additional methyl substituents on the aromatic rings. The high degree of preorganization afforded by these qualities further allowed the facile preparation of macrocyclic sheet structures from their non cyclic precursors. These macrocycles were shown to have slow internal dynamics and defined conforma-tional preferences. Using this background three and five-stranded artificial beta-sheets were synthesized and their folded conformations extensively characterized in solution by NMR. The solid state structures of the three and five-stranded sheets were also elucidated in the solid state by x-ray crystallography and confirmed intramolecular pi-pi aromatic stacking

Assessing Stabilization through pi-pi Interactions in Aromatic Oligoamide beta-Sheet Foldamers

International audienceWe have recently introduced aromatic oligoamide beta-sheet foldamers based on rigid turn units and short linear strands that undergo intramolecular pi-pi stacking. 1 We now report that conformational stability in these structures can be reached using less rigid turn units and more extensive pi-pi interactions between longer linear strands. For this study, two-stranded sheets of variable length were prepared. Their conformation was assessed in solution by 1 H NMR and in the solid state by x-ray crystallography

Aromatic Oligoamide β‑Sheet Foldamers

A rational approach for the construction of multi-stranded artificial β-sheets based not on hydrogen bonding, but rather on π–π aromatic stacking, is presented. Using 4,6-dinitro-1,3-phenylenediamine units, rigid turns were designed that allow face-to-face π–π interactions between appended linear aromatic segments to be strong enough for folding in an organic solvent, but weak enough to prevent aggregation and precipitation. Solution and solid-state studies on a series of turn units showed that the desired degree of rigidity, resulting from hindered bond rotation, could be fine-tuned by the inclusion of additional methyl substituents on the aromatic rings. The high degree of preorganization afforded by these qualities further allowed the facile preparation of macrocyclic sheet structures from their noncyclic precursors. These macrocycles were shown to have slow internal dynamics and defined conformational preferences. Using this background, three- and five-stranded artificial β-sheets were synthesized and their folded conformations extensively characterized in solution by NMR. The solid-state structures of the three- and five-stranded sheets were also elucidated in the solid state by X-ray crystallography and confirmed intramolecular π–π aromatic stacking

Assessing Stabilization through π–π Interactions in Aromatic Oligoamide β‑Sheet Foldamers

We have recently introduced aromatic oligoamide β-sheet foldamers based on rigid turn units and short linear strands that undergo intramolecular π–π stacking (Sebaoun, L.; Maurizot, V.; Granier, T.; Kauffmann, B.; Huc, I. <i>J. Am. Chem. Soc.</i> <b>2014</b>, <i>136</i>, 2168). We now report that conformational stability in these structures can be reached using less rigid turn units and more extensive π–π interactions between longer linear strands. For this study, two-stranded sheets of variable length were prepared. Their conformation was assessed in solution by ¹H NMR and in the solid state by X-ray crystallography