The presence of cholesterol is critical in defining a dynamic lateral structure in pulmonary surfactant membranes, including the segregation of fluid-ordered and fluid-disordered phases. However, an excess of cholesterol has been associated with impaired surface activity both in surfactant models and in surfactant from injured lungs. It has also been reported that surfactant protein SP-C interacts with cholesterol in lipid/protein interfacial films. In the present study, we have analyzed the effect of SP-C on the thermodynamic properties of phospholipid membranes containing cholesterol and on the ability of lipid/protein complexes containing surfactant proteins and cholesterol to form and re-spread interfacial films capable of producing very low surface tensions upon repetitive compression-expansion cycling. We have also analyzed the effect of cholesterol on the structure, orientation and dynamic properties of SP-C embedded in physiologically relevant model membranes.

The presence of cholesterol is critical in defining a dynamic lateral structure in pulmonary <p>surfactant membranes, including the segregation of fluid-ordered and fluid-disordered phases. <p>However, an excess of cholesterol has been associated with impaired surface activity both in <p>surfactant models and in surfactant from injured lungs. It has also been reported that surfactant <p>protein SP-C interacts with cholesterol in lipid/protein interfacial films. In the present study, we <p>have analyzed the effect of SP-C on the thermodynamic properties of phospholipid membranes <p>containing cholesterol and on the ability of lipid/protein complexes containing surfactant <p>proteins and cholesterol to form and re-spread interfacial films capable of producing very low <p>surface tensions upon repetitive compression-expansion cycling. We have also analyzed the effect of cholesterol on the <p>structure, orientation and dynamic properties of SP-C embedded in physiologically relevant <p>model membranes. <p><p> / Doctorat en Sciences / info:eu-repo/semantics/nonPublished

Au cours de cette thèse, nous nous sommes intéressés à l'activation de liaisons C-H catalysée par des catalyseurs au palladium pour la préparation de biaryles portant un groupement SO₂R. De très nombreux composés biologiques possèdent une fonction SO₂R. Nous avons donc choisi d'étudier activation de liaisons C-H de ce type de substrat. L'activation de liaisons C-H est considérée comme attractive pour l'environnement par rapport à d'autres types de couplages tels que Suzuki, Stille, ou Negishi. D'abord, nous avons démontré qu'il est possible d'appliquer la méthode d'activation de liaisons C-H pour l'arylation directe de thiophènes portant un substituant SO₂R. Nous avons ensuite établi un système catalysé au palladium pour l'arylation sélective en C2 de dérivés N-tosylpyrrole. Nous avons constaté que le N-tosylpyrrole est plus réactif comparé au pyrrole non protégé. Nous avons également étudié l'arylation directe d'hétéroarènes par des bromobenzènes possédant un substituant SO₂R soit en C2 ou C4 par catalyse au palladium. Cette méthode fournit un accès simple à des dérivés de ArSO₂R. Enfin, nous avons développé la première méthode de déshydrogénation de liaisons sp³ C-H catalysée au palladium de N-alkyl-benzènesulfonamides pour produire des N-alcényle benzènesulfonamides. / During this Ph.D. period, we were interested in the C-H bonds activation catalysed by palladium catalysts for the preparation of biaryls units bearing SO₂R group. Many biological compounds present a SO₂R function and thus we chose to activate this family of substrates. This method is considered as cost effective and environmentally attractive compared to other types of couplings such as Suzuki, Stille, or Negishi. First, we demonstrated that it is possible to apply C-H bond activation method for the direct arylation of thiophene derivatives bearing a SO₂R substituent. We then established palladium-catalysed system for the selective C2 arylation of N-tosylpyrrole derivatives. We found that N-tosylpyrrole is more reactive than free NH-pyrrole. We also studied the direct arylation of heteroarenes using bromobenzenes bearing SO₂R substituents either at C2 or C4 via palladium-catalysed C-H activation. This method provides a simpler access to substituted SO₂R derivatives. Finally we developed the first palladium-catalysed dehydrogenative sp³ C-H bond functionalization/activation of N-alkyl-benzenesulfonamides to produce N-alkenyl-benzenesulfonamides. The reaction proceeds with easily accessible ligand-free Pd(OAc)₂ catalyst for aryl bromides bearing electron-withdrawing groups or PdCl(C₃H₅)(dppb) catalyst for aryl bromides with electron-donating substituents. We found that the reaction tolerates a variety of substituents both on nitrogen and on the bromobenzene moiety.