Many emerging technologies would greatly benefit from reliable methods for the production of functional materials with well-defined 3D nanoscale structure. Conceptually, approaches to produce such architectures are divided into two broad classes; top down and bottom up manufacture. In the top down approach, nanoscale structure is created through the controlled removal of material from a bulk starting object. Top down methods have a proven record of reliability in the fabrication of extended two dimensional arrays with fine control over nanoscale features. However, such approaches become increasingly cumbersome when attempting to define structure in three dimensions rather than two. Bottom up methods promise a more reliable route to the formation of such materials. Here, molecular scale building units self-assemble to form a desired structure, driven by pre-defined interactions between individual motifs. Due to the highly specific molecular recognition properties of nucleic acids, along with their relatively simple synthesis and wide range of potential chemical modifications, DNA nanotechnology is now regarded as a prime route for the bottom up fabrication of nanostructured materials. However, current approaches to the formation of designed 3D DNA crystals are complicated by the difficulties in designing sub-units able to assemble in a predictable fashion over length-scales orders of magnitude larger than themselves. Amphiphiles are able to self-assemble into a variety of 3D crystalline phases driven by the frustrated micro-phase separation of hydrophobic and hydrophilic domains, with the structural properties reliant primarily on overall topology of the molecules rather than their exact chemical and geometrical features. Although the mechanism underlying amphiphile self-assembly is robust, it inherently limits control over the fine-scale structural details. This thesis reports on a new class of self-assembling DNA motifs; amphiphilic cholesterol-functionalised DNA nanostars, \emph {C-stars}. C-stars combine key advantages of all-DNA motifs and conventional amphiphilic molecules -- allowing for the preparation of expanded crystalline frameworks with tunable properties and embedded functionality.

Cette thèse s’inscrit dans une thématique de recherche visant à synthétiser des moléculesamphiphiles présentant des propriétés bioactives, pouvant être mises à profit dans diversesapplications biomédicales ou encore dans le domaine de l’agrochimie. Les molécules amphiphilessont alors les propres actrices de leur formulation de par leurs propriétés d’auto-association et debioactivité (concept dit « d’économie moléculaire »). Dans ce contexte, la première partie de cetravail a été consacrée à la synthèse de molécules amphiphiles modèles dérivées de D-glucose etde N-acétyl-D-glucosamine. La voie de synthèse choisie pour les obtenir a été une aminationréductrice régiosélective à partir de chaînes alkylamine de différentes longueurs (6, 12 et 16atomes de carbone). Leur caractérisation a été réalisée par RMN et spectrométrie de masse. Ladeuxième partie de ce travail a été orientée vers l’étude du comportement auto-associatif desmolécules à base de D-glucose en solution aqueuse, seules, ou en mélange avec un phospholipidemodèle. Une organisation à différentes échelles de taille a été mise en évidence par les techniquesde diffusion de la lumière, microscopie électronique en transmission et grâce à la modélisation dedonnées expérimentales obtenues en diffusion des rayons X aux petits angles. / This work is part of a research program on the synthesis of amphiphilic molecules havingbioactive properties, which could be used in biomedical applications or in agrochemistry.Amphiphilic molecules could be the own actor of their formulation because of the dual propertyof bioactivity and self-assembly. In this context, the first part of this work concerns the synthesisof model amphiphilic molecules derived from D-glucose and N-acetyl-D-glucosamine. The chosenway to synthesize these molecules was a regioselective reductive amination from alkylaminechains of different lengths (6, 12 and 16 carbon atoms). Compounds were characterized by NMRand Mass Spectrometry. The second part of this work was oriented towards the study of the selfassemblyproperties of molecules derived from D-glucose in an aqueous solution, alone, or mixedwith a model phospholipid. An organization with different sizes was shown with severaltechniques: light diffusion, transmission electronic microscopy, and thanks to the establishment ofa model from experimental small-angle X-ray scattering data. When the amphiphilic moleculewith 12 atoms of carbon on this hydrocarbonated chain is studied alone in a solution, ellipsoidalmicelles seem to be present, mixed with bigger aggregates (~100 nm). However, when this sameamphiphilic molecule is used in a mix with a model phospholipid, a size diminution of theassembly was observed with the increase of amphiphilic molecules in the formulations.

[pt] O coeficiente de partição octanol-água do composto 1,2-dipalmitoilsn-glicero-3-fosfatidilcolina (DPPC) foi investigado utilizando os métodos de integração termodinâmica e amostragem guarda-chuva através de simulações de dinâmica molecular atomística. Os campos de força AMBER/GAFF e CHARMM/CGenFF foram usados com seis modelos de água (SPC, TIP3P, TIP4P, TIP5P, OPC3 e OPC4) amplamente utilizados em simulações de dinâmica molecular. Dentre os modelos utilizados, o modelo de água OPC4 com os dois campos de força em estudo forneceu a melhor concordância com o coeficiente de partição experimental octanol-água do DPPC. No entanto, ainda existe muito espaço para melhorias nos modelos de água que estimam a tensão superficial de forma apropriada. Usando o modelo de água OPC4, a energia livre de Gibbs de transferência do DPPC do octanol para a fase aquosa foi calculada em 19,8(mais ou menos)0,3 e 20,2(mais ou menos)0,3 kcal mol-1 , estimando um coeficiente de partição octanol-água de 14,5(mais ou menos)0,4 e 14,8(mais ou menos)0,3 para os campos de força AMBER/GAFF e CHARMM/CGenFF, respectivamente. A amostragem guarda-chuva apresentou problemas de arrastes de moléculas de uma fase para outra, gerando artefatos e consequentemente subestimando os valores de energia livre e de coeficiente de partição octanol-água. Este estudo mostra a importância do desenvolvimento de novos modelos de água que reproduzam com precisão todas as suas características experimentais. A conciliação entre medições experimentais e cálculos teóricos do coeficiente de partição de moléculas anfifílicas poderia ser resolvida através do ajuste dos parâmetros do modelo de água. Este estudo possui grande importância na simulação de propriedades moleculares de importância em muitas áreas de aplicações científicas e industriais, tais como biofísica, surfactante, coloides, membranas, medicina, nanotecnologia, e indústrias alimentícias e farmacêuticas. / [en] The octanol-water partition coefficient of the compost 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) molecule wasinvestigated using the methods of thermodynamic integration and umbrellasampling through atomistic molecular dynamics simulations. TheAMBER/GAFF and CHARMM/CGenFF force fields were used with sixwater models (SPC, TIP3P, TIP4P, TIP5P, OPC3, and OPC4) widely usedin molecular dynamics simulations. Among the models used, the OPC4water model with the two force fields provided the best agreement with theexperimental octanol-water partition coefficient of the DPPC. However,there is still much room for improvement in water models that correctlyestimate the surface tension. Using the OPC4 water model, the Gibbs freeenergy of transferring DPPC from octanol to the aqueous phase wascalculated to be 19.8(plus minus)0.3 and 20.2(plus minus)0.3 kcal mol-1, estimating an octanolwater partition coefficient of 14.5(plus minus)0.4 and 14.8(plus minus)0.3 for the AMBER/GAFFand CHARMM/CGenFF force fields, respectively. Umbrella samplingpresented issues of molecules being dragged between the two phases,generating artifacts, and consequently underestimating the values of freeenergy and octanol-water partition coefficient. This study shows theimportance of developing new models of water that accurately reproduceall its experimental characteristics. The reconciliation betweenexperimental measurements and theoretical calculations of partitioncoefficients of amphiphilic molecules. This study may have greatimportance in many areas of scientific and industrial applications, such asbiophysics, surfactant, colloids, membranes, medicine, nanotechnology,and food and pharmaceutical industries.