Doctor of Philosophy / Department of Chemistry / Duy H. Hua / The discovery of new methodologies to advance the fields of synthetic organic, nanoclusters, and polymer chemistry is critical in the asymmetric synthesis of organic compounds. Particularly, catalytic asymmetric oxidation reactions are economic. The oxidation reactions provide chiral molecules and additional functionality onto the molecules for functional group manipulation. New kinds of polymers, namely chiral-substituted poly-N-vinylpyrrolidinones (CSPVPs), stabilize the bimetallic nanoclusters such as Pd/Au or Cu/Au and induce chirality. These chiral polymers wrap around the nanometer-sized (~3 nm) bimetallic nanoclusters and catalyze a number of enantioselective oxidation reactions using oxygen or hydrogen peroxide as the oxidant. Cycloalkanediols were asymmetrically oxidized by 1 atm of oxygen gas to yield the corresponding hydroxyl ketone under the catalysis of Pd/Au (3:1) – CSPVP nanoclusters. Alkenes were oxidized by Pd/Au (3:1)-CSPVP nanoclusters under 2 atmospheric of oxygen in water to give the syn-dihydroxylated products in high chemical and excellent optical yields. Various cycloalkanes underwent regio- and enantio-selective C-H oxidation with Cu/Au (3:1)-CSPVP and 30% hydrogen peroxide to produce the corresponding chiral oxo-molecules in very good to excellent chemical and optical yields. We further discovered an enantioselective desymmetrization of , -dialkenyl-alkanols and , -dialkenyl-amino acid ethyl esters to give chiral disubstituted lactones and lactams, respectively. A number of medium-sized natural products and drugs were also oxidized regioselectively to give the corresponding mono-oxygenated products. A broad-spectrum predictive C-H oxidation of complex molecules is possible. Chapter 1 mainly discussed the synthesis and characterization of the new classes of chiral substituted PVP and bimetallic nanoclusters. Chapter 2 focus on various kind of oxidation reactions by the catalysis of CSPVP stabilized bimetallic nanoclusters. Among various bioluminescence assays, firefly luciferase based bioluminescence assays are popular due to their high specific activity, low background noise and ease of use. However, it has been found that some aromatic carboxylic acid substantially inhibited the firefly luciferase reporter enzyme’s activity. In order to study firefly luciferase inhibition and the proteins associated with inhibition mechanism, we designed two 6-(dimethylamino)-2-phenylisoindolin-1-one derivatives as probe molecules. The synthesis of one probe molecule is discussed in Chapter 3 and the further investigation of its inhibitory activity on firefly luciferase is being conducted by our collaborate.

Nanoscale particles based on the nature of building blocks often self-assemble into superstructures with distinctive spatial arrangements which can be used as functional materials for different application. Micro-phase separated hairy nanoparticle with helical hair can self-assemble to form supramolecular material which may mimic the properties and functions of the natural polymers such as protein and cellulose. Beside this hairy/core-shell nanoparticles also may find many applications such as in asymmetric catalysis, nano-fillers in tire and rubbers, model systems for biology, lithography and as sensors. In this work, we have successfully synthesized two hairy nanoparticles both of which has cross-linked polystyrene core with helical poly (3- methyl 4- vinyl pyridine) and poly (2- methoxystyrene) brushes respectively by living anionic polymerization via one-pot synthesis. NMR spectroscopy was used to determine that polymerization was successful and compositions of HNPs have the agreement with the targeted HNPs structure. By tailoring the architecture (functionalization of polymer chains, the degree of polymerization, grafting density) of HNPs, it is possible to control the final properties of the system. Differential Scanning Calorimetry was used to demonstrate the thermal properties of the synthesized HNPs which corresponds to polymer composition. Dynamic light scattering, SEM and AFM images were recorded to measure the particle size and morphology of the particles. Circular dichroism spectroscopy was used to determine the induced chirality of helical polymer brushes by complexing it with the small chiral molecule. SEM and AFM imaging were recorded to find out the morphology and hierarchically self-assembly of the hairy nanoparticle system. The synthesized particles may have great potential to successfully generate self-assembled suprastructures which can further solve the chiral resolution problem and can also find different applications.

Depuis une quinzaine d’années, les polymères chiraux sont utilisés dans de nombreuses applications, comme phases stationnaires pour la séparation d’énantiomères ou encore en tant que catalyseurs en synthèse asymétrique. Aux vues de ces intérêts grandissants, de nombreuses méthodes ont émergé afin de les synthétiser. Nous nous sommes concentrés sur des méthodes organocatalytiques originales de synthèse de polymères chiraux par réaction de polyaldolisation et par désymétrisation de bis-anhydrides. Nous avons ainsi développé des processus de désymétrisation itératifs et ainsi généré une chiralité C-centrée sur la chaine polymérique. Des polyesters chiraux ont ainsi été obtenus avec de très bonnes séléctivités. / Chiral polymers are used in many applications such as stationary phases for chiral HPLC and catalysts in asymetric synthesis. The synthesis of chiral polymers traditionally deals with metal catalysts-based methodologies and often involved sensitive substrates. On the other hand, only a limited number of publications has been reported through environmentally-friendly organocatalytic pathways.The goal of this Ph.D. studies was devoted to the design of new routes toward chiral polymers under organocatalysis. We chose polyaldolisations and anhydride desymmetrizations with alcohols as key reactions to obtain original polymers with a C-centered chirality in the main polymer chain.