As aplicações do ZrO2 dependem das suas fases cristalinas e muitos estudos têm sido realizados sobre suas transições e os aditivos empregados no seu controle. No entanto, os mecanismos atuantes em tais processos são explicados com base exclusivamente cinética desconsiderando a contribuição termodinâmica que os aditivos exercem sobre as energias dos polimorfos e suas superfícies. Neste trabalho, o efeito termodinâmico do MgO sobre as transformações de fases é estudado para pós de ZrO2 preparados por uma rota química derivada do método Pechini. Análises de picnometria, área de superfície específica, difração de raios X, espectroscopias de infravermelho, Raman e de fotoelétrons excitados por raios X, além de amplitude sônica eletrocinética foram empregadas para caracterizar a evolução das fases formadas. Verifica-se que quantidades crescentes de MgO desestabilizam a fase monoclínica e tornam a fase tetragonal estável. A fase cúbica é encontrada para grandes quantidades de MgO. As transformações de fases marcam descontinuidades em características como área de superfície específica devido a alteração de simetria cristalina. O MgO, na forma de periclásio, não foi observado para quantidades inferiores a 40 % molar. Levando-se em conta a baixa solubilidade do MgO no ZrO2 conclui-se que o controle das fases observadas possui pouca contribuição de processos cinéticos associados à formação de defeitos puntiformes. Resultados de XPS mostram que o íon Mg2+ localiza-se tanto na rede cristalina quanto na superfície do ZrO2. A sua segregação é atribuída a um efeito termodinâmico que resulta na diminuição da energia de superfície do ZrO2 promovendo o desenvolvimento de um excesso de superfície, confirmado pelas medidas de área de superfície específica, com a conseqüente diminuição do tamanho de partícula. Tais conclusões implicam que ambos os efeitos termodinâmicos e cinéticos devem ser considerados no controle do polimorfismo do ZrO2. / The applications of ZrO2 depend on its cristalline phases and several studies have been carried out about its transitions and the additives used to control it. However, the active mechanisms in such processes are explained with an exclusively kinetic basis disregarding the thermodynamic contribution that the additives exert over the polimorphs and surface energies. In this work, the thermodynamic effect of MgO on phase transformation is reported for ZrO2 powders prepared by a chemical route derived from Pechini\'s method. Picnometric, specific surface area, X-ray diffraction, infrared, Raman and X-ray photoelectron spectroscopies, besides electrokinetic sonic amplitude experiments were performed to characterize the evolution of the formed phases. It is verified that crescent amounts of MgO desestabilize the monoclinic phase and make stable the tetragonal. The cubic phase is found for large amounts of MgO. The phase transformations appoint descontinuities as the specific surface area due to crystalline simmetry change. The MgO, in the periclase form, wasn?t observed for amounts lower than 40 molar %. Taking into account the low solubility of MgO into ZrO2 it is concluded that the control of the observed phases has a low contribution to kinetic processes associated to point defects formation. XPS data show that Mg2+ ion is located onto the bulk as far as the ZrO2 surface. Its segregation is assigned to a thermodynamic effect resulting in a decrease of ZrO2 surface energy, which promotes the development of a surface excess, upholded by specific surface area measurements, with the consequent decrease of particle size. Such conclusions impose that both thermodynamic and kinetic effects must be considered on the control of ZrO2 polimorphism.

Foram realizadas análises por espectros absorção, fluorescência e excitação para anilina e orto-toluidina em água, com e sem a adição de HCl. Os resultados indicam que as propriedades do meio dependem das concentrações de amina e de HCl, sendo observado principalmente pelos espectros de excitação de fluorescência. Espectros de 1H RMN parecem indicar um efeito de agregação destas moléculas pelas mudanças observadas na forma e na posição dos sinais dos prótons. Foi realizada a síntese de polianilina e de poli-o-toluidina, sendo o acompanhamento efetuado por espectroscopia ultravioleta-visível e pela técnica de perfil de potencial, indicando similaridades entre os dois métodos. As sínteses de polianilina e de poli-o-toluidina também foram realizadas via fotoquímica, sendo os produtos de reação caracterizados por espectroscopia ultravioleta visível e por infravermelho. / The aim this work was to study aniline and orto-toluidine in aqueous solution with or without HCl addition. The analyses were realized by absorption and fluorescence spectrum. The results show that the proprieties are relation on amines and chloridric acid concentrations, especially it was observed by fluorescence excitation spectrum. Changes in protons sign position and in the form can be indicating an effect of aggregation with these molecules though 1H RMN spectrum. UV-Vis spectroscopy and open circuit potential measurements were used for monitor the synthesis of polyaniline and the poly-o-toluidine. Theses methods show similar results. Also, the synthesis of polyaniline and the poly-o-toluidine were realized by photochemistry via, which the reaction products were characterized by UV-Vis spectroscopy and FTIR.

Hydroxyapatite (HAP) coatings are used in orthopaedic surgery for bone regeneration. Current methods of phase quantification of HAP coatings suffer from drawbacks. A novel methodology of quantitative phase analysis of HAP coatings has been devised and validated. This method, based on whole pattern fitting with a fundamental parameters approach, incorporates amorphous calcium phosphate (ACP) and apatite phases into structural refinements. A comparison of the structural and chemical properties of plasma sprayed (PS) and novel electrodeposited (ED) HAP coatings has been conducted. ED coatings contained less ACP and more preferred orientation than the PS coatings, although the stoichiometry was similar. In vitro investigations of PS and ED coatings in simulated body fluid and foetal calf serum revealed that both are bioactive. A carbonated apatite layer produced on the ED coatings was -0.7μm thick with a stoichiometry and chemical constituents similar to that of natural bone apatite. PS coatings produced a nanocrystalline carbonated apatite layer (-4μm). For the first time it has been possible to model crystalline HAP and nanocrystalline apatite as independent phases and obtain accurate lattice parameters for each. A positive linear correlation has been made between microstrain and the solubility of HAP and carbonated apatites. Dissolution studies have shown that the behaviour of HAP and carbonated apatite is dominated by crystallite size at low undersaturation and by crystallite size and microstrain at high undersaturation for crystallites between -30OA- 1000A. Metastable equilibrium occurred for crystallites <_400A at low undersaturation. Carbonate content did not affect the solubility or dissolution behaviour. A novel technology for coating polymeric tape with HAP for potential use in anterior cruciate ligament reconstruction has been devised. Mechanical tests have demonstrated that no adverse properties are induced by the coating technology. Cell culture studies have shown that the HAP layer is capable of enhanced attachment, proliferation and differentiation of osteoblast cells compared to uncoated tape.

L'acide ascorbique (AA) a longtemps été décrit comme un agent antiprolifératif, mais la molécule doit être utilisée à très fortes doses, nécessitant des injections intraveineuses. La régulation stricte et complexe des concentrations sanguines et cellulaires rendent impossible le maintien des concentrations élevées sur une longue période.Avec la société KaïronKem, nous avons créé une chimiothèque de dérivés de l'AA. Le but de ce travail thèse était d'identifier des molécules dérivées dont l'action antiproliférative est supérieure à celle de l'AA. Parmi elles, nous avons sélectionné la plus prometteuse, K873, qui a montré des effets cytotoxiques et antiprolifératifs sur différentes cellules tumorales humaines à une dizaine de micromolaires, tout en étant non-toxique pour les cellules saines. Nous avons ensuite testé son efficacité in vivo grâce à des injections quotidiennes chez des souris immunodéficientes xénogreffées avec des cellules cancéreuses humaines. K873 a montré une action antiproliférative sur la progression tumorale équivalente à l'AA à des doses 100 à 200 fois inférieures.Nous avons étudié le mécanisme d'action de K873. Tout comme l'AA, il diminue l'expression de deux familles de gènes impliqués dans la progression du cycle cellulaire : facteurs d'initiation de la traduction et ARNt synthétases. Nos résultats montrent que le transporteur intracellulaire de l'AA (SVCT2) n'est pas utilisé pour l'entrée de K873 dans la cellule, bypassant ainsi sa saturation. De la même façon que l'AA, K873 diminue le niveau intracellulaire d'AMPc mais en n'ayant aucune activité antioxydante. Les dérivés de l'AA pourraient être une nouvelle classe de médicaments anticancéreux. / Ascorbic acid (AA) was long described as an antiproliferative agent. However, the molecule has to be used at very high concentrations, which necessitates intravenous injections. In addition, the tight regulation of in-blood and in-cell AA concentrations makes it impossible to hold very high concentrations for any substantial length of time.In collaboration with KaironKem, we undertook the creation of a focused chemical library of AA derivatives. The aim of this work was therefore to identify derivatives molecules with antiproliferative action higher than AA. Among these new molecules, we selected K873 that has cytotoxic and antiproliferative effects on different human tumor cells at tenth micromolar concentration, without being toxic for normal cells. We then tested in vivo the effect of treatment with K873's daily injections in xenografted immunodeficient mice with human cancer cells. K873 showed an antiproliferative effect on tumor growth similar to AA but at doses 100 to 200 times lower.Finally we studied the mechanism of action of K873. As AA, it decreases the expression of two genes families involved in cell cycle progression, i.e. initiation factor of translation and tRNA synthetases. Our results also showed that the specific intracellular transporter of AA (SVCT2) is not used for K873 entry in cells, thus bypassing saturation. Finally, as AA, K873 reduced cAMP intracellular level but without antioxidant activity. Our findings suggest that AA derivatives could be a promising new class of anti-cancer drugs.

Decytospolides A and B are natural products isolated from Cytospora sp. No ZW02 that show mild anticancer properties. The interest in synthesizing these compound lies not in their activities, but rather the simplicity of the structure which could easily be modified to provide more potent derivatives. Previous syntheses of these compounds relied on transition metals to install the tetrahydropyran core or extensive use of protecting groups. Our first generation synthesis made use of the Achmatowicz rearrangement to synthesize the tetrahydropyran moiety. Based on this, a concise, protecting group free synthesis has been accomplished utilizing the Achmatowicz rearrangement of an optically active furanyl alcohol followed by diastereoselective Kishi reduction of the resulting dihydropyranone hemiacetal. <br><br>Carambolaflavone A is a natural product isolated from A. carambola with antidiabetic properties. Notably, these compound promote both insulin secretion and glucose uptake by muscle cells in hyperglycemic rats. A previous synthesis has been reported by Wang and coworkers, however this synthesis does not offer much potential for the formation of derivatives and relies on a C-glycosylation that requires heating for regio- and diastereoselectivity. Progress towards a concise synthesis has been made featuring a Lewis acid promoted highly diastereoselective substrate controlled C-glycosylation that does not require heating and a one pot oxidation of chroman to chromone utilizing DDQ. Further research is underway to complete the synthesis of this molecule by an oxidative addition to the chromone and subsequent removal of protecting groups.

<p>  </p> <p>Biosynthesis of fatty acids and specialized metabolites, such as polyketides, is dependent on the C-C bond forming enzymatic activity of carboxylases and <u>k</u>eto<u>s</u>ynthases (KS). Carboxylases and KS perform complex carbon-carbon bond forming reactions via a ping-pong mechanism; the catalytic interactions of which are still unclear. The KS reaction involves the Claisen condensation of an acylated enzyme with a malonyl-thioester, driven forward by the energy of the malonyl-thioester decarboxylation. Similarly, the carboxylase proceeds via a carboxyl-biotin-enzyme intermediate, and a subsequent C-C bond forming reaction. Engineering the substrate specificity of these enzyme involved in producing polyketides is sought after for the purpose of producing novel, derivative polyketides. These derivative polyketides may have serve as effective new antibiotics, of which discovery has waned. Unfortunately, incomplete understanding of protein-protein interactions, conformational changes, and substrate orientation in catalysis leads to not well informed engineering attempts. A challenge in deducing the catalytic details of enzymes acting on malonyl-thioesters in general is the hyper-reactivity of their β-ketoacid and thioester substrates, which are prone to hydrolysis and decarboxylation. Many structures of malonyl-CoA bound enzymes feature hydrolysis of the thioester, preventing determination of enzyme:substrate interactions in structure-function studies. To work around this problem of innate reactivity, groups have synthesized a variety of acyl-thioester analogs for probing the details of enzyme catalysis with mixed success. The success of these enzyme:analog mechanistic studies appears to hinge upon the similarity of the analog to the natural substrate. Here, we demonstrate the synthesis of near-natural, acyl-thioester analogs, featuring single atom substitutions. Using a novel UV-vis assay, we have determined <em>K</em>i values of our analogs with paradigmatic KSs <em>E. coli</em> FabH. These <em>K</em>i values are marginally higher than the substrate <em>K</em>m values, suggesting the KSs bind the analogs as they would natural substrates. Using this information, we have conducted preliminary X-ray crystallography experiments to determine the carboxylase:analog and KS:analog catalytic interactions, which will allow for new insight into debated C-C bond forming catalytic details. The information presented in this thesis and additional studies on protein-protein interactions can be leveraged into informed engineering studies of PKS enzymes.</p>

<p>  </p> <p>Plastics play crucial rules in almost every aspect of life. Unique properties of plastics like chemical and light resistant, strong, moldable, and low cost make plastic materials useful in many aspects of our global society. However, largely relying on feedstock resources like fossil fuels, plastics production is not sustainable. Thus, plastic recycling could be an efficient alternative to save feedstock resources as well as to reduce production cost.</p> <p>Recently, a series of polymer materials synthesized via topochemical polymerization are considered as strong candidates for next generation recyclable plastics. It is well-known that topochemical polymerization has high efficiency and environment-friendly features, such as solvent-free and catalyst-free reaction conditions, high reaction yield without side reactions, and atom economy. Yet, there exist few studies on depolymerizing and recycling those polymers. A unique topochemically polymerizable polyindenedione derivative [2,2'-Bi-1H-indene]-1,1'-dione-3,3'-diyl dialkylcarboxylate (polyBIT) with rapid and quantitative depolymerization was discovered via breakage of elongated carbon-carbon (C-C) bonds with bond length of 1.57∼1.63 Å. The elongated C-C bonds have been proven theoretically and experimentally to have significantly lower bond dissociation energies than normal C-C bonds, and it is the major driving force to depolymerize polyBIT polymer single crystals. </p> <p>Different from most traditional polymers that can be dissolved or melt processed, topochemical polymer single crystals are not soluble in most common solvents due to their highly crystalline and ordered nature. This unique feature inhibited topochemical polymer crystals from practical applications. To convert needle-like polyBIT crystals into useful forms, I developed an ultrasonication method to break large polymer crystals into small fibers that can be uniformly suspended in organic solvents. Followed by vacuum filtration and heat press, polyBIT crystals can be processed into robust and freestanding polymer thin films. The processed thin films presented reasonable mechanical properties with Young’s modulus of over 600MPa and are stable under harsh conditions.</p> <p>Topochemical polymerization reactions require specific monomer packings before applying external stimuli, and a small change in monomer structure may completely alter the reactivity. Therefore, functionalizing monomer structures for topochemical reactions is quite challenging. In the polyBIT system, we attempted to functionalize BIT monomer with several linear and branched side chains. After preparing monomer crystals, only needle-like 1D monomers can be photopolymerized, while plate-like 2D monomer crystals became photostable. Introducing heteroatoms (such as oxygen, sulfur, bromine, chlorine) can induce different non-bonding interactions and interactions, which combined can push monomers away from one another to make them unreactive. Introducing branched side chains will also change the distances between two BIT monomers and leads to unreactive crystals when the branched side chain is too bulky (such as when tertbutyl group is on the end of side chain). Functionalizing side chains for polyBIT crystals can further tune the mechanical properties of the crystals: swapping end methyl group with a simple bromine atom can induce multiple intermolecular and interchain interaction including weak hydrogen bonding and C−H···Br interactions. These interactions bind all the polymer chains together to provide a strong 1D polymer fiber with elastic modulus over 10.6 GPa. These results suggest that the crystalline polymers synthesized from simple photochemistry and without expensive catalysts are promising for practical applications with complete materials circularity and wide range of structural and mechanical turnabilities.</p>

<p>  </p> <p>The access of ring junction functionalized 5,6-hydrindanone systems has been elusive in the realm of synthetic methodology, and the functionalization of a pre-built ring system rarely explored. These 5,6-hydridanone systems are prevalent in a variety of terpenoid ring systems, especially that of steroidal molecules. Previous synthetic methods to reach these systems using a Diels-Alder cycloaddition proved to be difficult and lacked labile functional groups that would be useful for substitution after the cycloaddition. The design of the α-nitrile cyclopentenone dienophile allows for both post-cyclization adduct functionalization, as well as lowering the energy barrier of the cycloaddition itself. In this work, it is shown that the Lewis acid promoted Diels-Alder reaction with α-nitrile β-methyl cyclopentenone dienophile can be performed under standard temperatures and pressures unlike previously established methods.1 This reaction can generate four chiral centers in a single synthetic step when the starting materials are prochiral. After the generation of 5,6-hydrindanone systems, radical cleavage of the nitrile functionality also allowed for electrophile trapping at the ring junction. This radical cleavage and electrophile trapping pathway allows for functionalization of a quaternary carbon at the ring junction, a method that should be fruitful in the generation of difficult to synthesize steroidal and other terpenoid molecules.</p> <p>In the work on synthetic cell penetrating peptides, camptothecin whilst a notably effective topoisomerase I inhibitor, has never quite reached it’s potential as a therapeutic due to its poor solubility in living systems. Previously, cationic amphiphilic polyproline helices (CAPH) molecules from the Chmielewski lab have been hydrophobically functionalized through O-alkylation of hydroxyprolines at specific regions within the peptide to generate a hydrophobic face. The combination of the cationic faces and the hydrophobic face have made the CAPH molecules notably cell penetrant and tunable. With camptothecin’s notable insolubility in water, it may serve as valuable surrogate to the hydrophobic groups on CAPH molecules and allowing it to be delivered intracellularly. Using an endogenously cleavable linker, we have worked towards a CPP that acts as a drug delivery vehicle. Acting as a replacement of the hydrophobic residue of a CAPH molecule, camptothecin will be chaperoned into the cell and should be released through the action of intracellular esterases.</p>

<p>Total synthesis of massarinolin A, purpurlides B, D, E, 2,3-deoxypurpurolide C, phleghenrines A and B were finished. A halogen bond promoted michael addiation was discovered during mechanism study toward diamination of allenes. Computational chemsitry study conducted toward the selectivity of 2+2 reaction supported the proposed key reaction during total synthesis of gibberellic acid 18.</p>

<p> 2-Tetrazens are often used as high energy-density materials. Only a few synthetic methods  exist for making them. Further, their structure-property relationships remain largely unexplored.  Asphaltenes are usually a complex mixture found in the heaviest fraction of heavy crude oil. Their structural characterization and understanding have become a pertinent task for petroleum industry  around the world. Mass spectrometry is a powerful analytical tool for the detection and  characterization of unknown compounds even in complex mixtures. It features high sensitivity and  speed and can provide a variety of valuable information for different types of analytes. This thesis  focuses on the development of an effective synthetic method for 2-tetrazenes and the mass  spectrometry study of the ionized 2-tetrazenes. In addition, the mass spectrometric behavior of  ionized asphaltene model compounds are also discussed in this thesis. Chapter 2 describes the instrumentation and fundamental aspects of the mass spectrometers used in the research discussed in this thesis. Chapter3 introduces an effective synthetic method for  2-tetrazens based on iodine-mediated oxidative N-N coupling reaction of hydrazines. Chapter 4  presents the fragmentation behavior of ionized 2-tetrazenes in tandem mass spectrometry experiments. Upon collision-activated dissociation (CAD), ionized alkyl-substituted linear 2- tetrazenes underwent simpler fragmentation reactions than the ionized aromatic 2-tetrazenes or a  cyclic 2-tetrazene. The observations were rationalized by using quantum chemical calculations.  Chapter 5 presents the fragmentation behavior of ionized asphaltene model compounds under  medium-energy collision-activated dissociation (MCAD). The comparison between the different  behaviors of the molecular radical cations of these compounds provided useful information for the  identification of related unknown compound </p>