The Effective Field Theory formalism is applied to the study of problems in hadronic and nuclear physics. We develop a framework to study the exclusive two-body decays of bottomonium into two charmed mesons and apply it to study the decays of the C-even bottomonia. Using a sequence of effective field theories, we take advantage of the separation between the scales contributing to the decay processes, 2m(b) ≫ m(c) ≫∧(QCD). We prove that, at leading order in the EFT power counting, the decay rate factorizes into the convolution of two perturbative matching coefficients and three non-perturbative matrix elements, one for each hadron. We calculate the relations between the decay rate and non-perturbative bottomonium and D-meson matrix elements at leading order, with next-to-leading log resummation. The phenomenological implications of these relations are discussed. At lower energies, we use Chiral Perturbation Theory and nuclear EFTs to set up a framework for the study of time reversal (T) symmetry in one- and few-nucleon problems. We consider T violation from the QCD θ term and from all the possible dimension 6 operators, expressed in terms of light quarks, gluons and photons, that can be added to the Standard Model Lagrangian. We construct the low energy chiral Lagrangian stemming from different TV sources, and derive the implications for the nucleon Electric Dipole Form Factor and the deuteron T violating electromagnetic Form Factors. Finally, with an eye to applications to nuclei with A ≥ 2, we construct the T violating nucleon-nucleon potential from different sources of T violation.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Submitted in fulfillment of the requirements for the Doctor of Philosophy degree in Chemistry, Durban University of Technology, Durban, South Africa, 2016. / In drug discovery and development projects, metabolism of new chemical entities (NCEs) is a major contributing factor for the withdrawal of drug candidates, a major concern for other chemical industries where chemical-biological interactions are involved. NCEs interact with a target macro-molecule to stimulate a pharmacological or toxic response, known as pharmacodynamics (PD) effect or through the Adsorption, Distribution, Metabolism, and Excretion (ADME) process, triggered when a bio-macromolecule interacts with a therapeutic drug. Therefore, the drug discovery process is important because 75% of diseases known to human kind are not all cured by therapeutics currently available in the market. This is attributed to the lack of knowledge of the function of targets and their therapeutic use in order to design therapeutics that would trigger their pharmacological responses. Accordingly, the focus of this work is to develop cost saving strategies for medicinal chemists involved with drug discovery projects. Therefore, studying the synergy between in silico and in vitro approaches maybe useful in the discovery of novel therapeutic compounds and their biological activities. In this work, in silico methods such as structure-based and ligand-based approaches were used in the design of the pharmacophore model, database screening and flexible docking methods. Specifically, this work is presented by the following case studies: The first involved molecular docking studies to predict the binding modes of catechin enantiomer to human serum albumin (HSA) interaction; the second involved the use of docking methods to predict the binding affinities and enantioselectivity of the interaction of warfarin enantiomers to HSA. the third case study involved a combined computational strategy in order to generate information on a diverse set of steroidal and non-steroidal CYP17A1 inhibitors obtained from literature with known experimental IC50 values. Finally, the fourth case study involved the prediction of the site of metabolisms (SOMs) of probe substrates to Cytochrome P450 metabolic enzymes CYP 3A4, 2D6, and 2C9 making use of P450 module from Schrödinger suite for ADME/Tox prediction. The results of case study I were promising as they were able to provide clues to the factors that drive the synergy between experimental kinetic parameters and computational thermodynamics parameters to explain the interaction between drug enantiomers and thetarget protein. These parameters were correlated/converted and used to estimate the pseudo enantioselectivity of catechin enantiomer to HSA. This approach of combining docking methodology with docking post-processing methods such as MM-GBSA proved to be vital in estimating the correct pseudo binding affinities of a protein-ligand complexes. The enantioselectivity for enantiomers of catechin to HSA were 1,60 and 1,25 for site I and site II respectively. The results of case study II validates and verifies the preparation of ligands and accounting for tautomers at physiological pH, as well as conformational changes prior to and during docking with a flexible protein. The log KS = 5.43 and log KR = 5.34 for warfarin enantiomer-HSA interaction and the enantioselectivity (ES = KS/KR) of 1.23 were close to the experimental results and hence referred to as experimental-like affinity constants which validated and verified their applicability to predict protein-ligand binding affinities. In case study III, a 3D-QSAR pharmacophore model was developed by using 98 known CYP17A1 inhibitors from the literature with known experimental IC50 values. The starting compounds were diverse which included steroidal and non-steroidal inhibitors. The resulting pharmacophore models were trained with 69 molecules and 19 test set ligands. The best pharmacophore models were selected based on the regression coefficient for a best fit model with R2 (ranging from 0.85-0.99) & Q2 (ranging from 0.80-0.99) for both the training and test sets respectively, using Partial Least Squares (PLS) regression. On the other hand, the best pharmacophore model selected was further used for a database screening of novel inhibitors and the prediction of their CYP17A1 inhibition. The hits obtained from the database searches were further subjected to a virtual screening workflow docked to CYP17A1 enzyme in order to predict the binding mode and their binding affinities. The resulting poses from the virtual screening workflow were subjected to Induced Fit Docking workflow to account for protein flexibility during docking. The resulting docking poses were examined and ranked ordered according to the docking scores (a measure of affinity). Finally, the resulting hits designed from an updated model from case study III were further synthesized in an external organic chemistry laboratory and the synthetic protocols as well as spectroscopic data for structure elucidation forms part of the provisional patent specification. A provisional patent specification has been filed (RSA Pat. Appln. 2015/ 07849). The case studies performed in this thesis have enabled the discovery of non-steroidal CYP17A1 inhibitors. / D

Catalysis plays a key role in chemical conversions by making them faster and more selective. Despite its widespread use and decades of academic and industrial research, limited catalyst selectivity and stability still call for major improvements in catalyst performance to meet the demands of a sustainable society. Phosphine ligands are ubiquitous in transition metal chemistry and lead to extremely reactive and versatile homogeneous catalysts. Fast development of tailor-made catalysts and catalyst recovery are key issues in (asymmetric) homogeneous catalysis. Therefore libraries of ligands have to be synthesised and screened in an efficient way, which could be facilitated by Solid Phase Synthesis (SPS). Currently, most polymer bound ligands are anchored to the support after the synthesis in solution. However, the main advantages of synthesising the ligands directly on the polymeric support are not only easy catalyst recycling and product separation, but also the ease of purification during the synthesis steps, namely by simple washing and filtration. The use of SPS is very efficient for high throughput synthesis and screening of ligand libraries, however applications of SPS towards libraries of phosphorus ligands are rare, because the synthetic methodologies are still lacking. Here we present the development of methodologies towards novel immobilised bis(phosphine) ligands synthesised on polystyrene and JandaJel™ resin. By performing the synthesis steps on a solid support, the advantages of SPS are fully utilised. Successful routes have been developed towards immobilised secondary phosphine-boranes, which were versatile synthons to prepare a variety of new polymer-supported (C-chiral) bis(phosphine) ligands. These ligands were then tested for their catalytic activity in rhodium catalysed hydrogenation reactions.

La synthèse d'amines chirales par catalyse asymétrique à l'aide de complexes de métaux de transition suscite un grand intérêt, puisque cela conduit à la production de molécules à haute valeur ajoutée. La voie catalytique offre une alternative avantageuse par rapport aux voies de synthèses conventionnelles, dont les inconvénients sont d'une part des produits de départ coûteux et d'autre part un grand nombre de produits secondaires, sans parler des étapes de synthèse souvent nombreuses. Dans le cadre d'un projet industriel visant à développer des outils catalytiques performants pour la synthèse d'amines chirales, nous nous sommes orientés vers le développement d'un système qui permettrait de réaliser l'hydroaminométhylation d'alcènes de façon énantiosélective. L'hydroaminométhylation est une réaction tandem combinant deux réactions catalytiques, l'hydroformylation et l'hydrogénation. A partir de molécules modèles, nous avons développé une approche permettant de rationnaliser la création de centres asymétriques en fonction du type de substrat utilisé, soit au cours de l'hydroformylation, soit au cours de l'hydrogénation de l'énamine intermédiaire. La réaction a été étudiée en version intermoléculaire et intramoléculaire. Le cycle catalytique de l'hydroformylation et celui de l'hydrogénation possèdent chacun des exigences différentes au niveau de la sphère de coordination du métal. De plus, les conditions de la réaction tandem ont une influence sur les espèces catalytiques formées et les sélectivités de la réaction. Grâce à des études de RMN sous pression, confirmées par des calculs théoriques, nous nous sommes attachés à étudier le comportement des complexes du rhodium mis en jeu, sous pression et dans les conditions d'hydroaminométhylation. Ces études nous ont permis d'approfondir la connaissance des espèces catalytiques impliquées dans cette réaction tandem. L'ensemble du travail de recherche a été mené en combinant les approches fondamentale et appliquée, nous permettant ainsi de proposer un outil catalytique adapté au substrat de départ considéré, dans la perspective d'une application industrielle de la réaction. / Amines are of great importance as building blocks or reactants in the chemical industry. The development of catalytic processes for their synthesis is thus of particular interest from an industrial point of viewsince they can afford an alternative to conventional synthetic pathways. In the context of an industrial project aiming to synthesize chiral amines, we focused on the development of a catalytic system adapted to the asymmetric hydroaminomethylation of alkenes. This tandem reaction includes two transition metal catalyzed reactions under CO and H2 pressure: the hydroformylation and the hydrogenation reactions. Starting from model molecules, we proposed an approach to carefully study the creation of asymmetric centers during the reaction sequence, either in the hydroformylation step or in the enamine intermediary hydrogenation step. The reaction was studied in its inter- and intramolecular version.Rhodium is often used for the hydroaminomethylation reaction, since it is able to complete both catalytic cycles of hydroformylation and hydrogenation. However, requirements in the coordination sphere of the metal center and species involved in each catalytic cycle are presumed to be different. Thanks to high pressure NMR experiments, combined with DFT calculations, the behaviour of rhodium complexes involved in the catalysis was investigated under conditions close to those of hydroaminomethylation. The knowledge of the rhodium species involved in the reaction was also improved thanks to these spectroscopic and catalytic experiments. The fundamental and applied approaches result in a deeper understanding of the tandem reaction sequence and allow us to design a catalytic system adapted to the starting substrate, in the purpose of an industrial application of the reaction.

Este trabalho é resultado de uma série de estudos feitos com o objetivo de investigar a influ- ência de uma álgebra fermiônica deformada nos mecanismos de quebra e restauração da si- metria quiral no modelo de Nambu-Jona-Lasinio. Esse modelo foi escolhido pois é um modelo efetivo para a QCD que mostra com razoável facilidade uma de suas principais características, a quebra dinâmica da simetria quiral e a geração de uma massa dinâmica para os quarks. O trabalho pode ser dividido essencialmente em três partes. A primeira consiste em um estudo inicial onde a deformação foi implementada diretamente na equação de gap do modelo NJL através de um cálculo deformado do condensado. Na segunda parte, o mesmo procedimento de deformação foi aplicado na Hamiltoniana do modelo permitindo que seus efeitos se propagem nos cálculos até uma nova equação de gap. Uma extensão natural do trabalho e um estudo do modelo deformado a temperatura finita, onde a coexistência da temperatura e da deformação algébrica pode ser investigada. Esse estudo e a terceira parte do trabalho / This work is a result of a serie of studies where the aim is to investigate the influence of a de- formed fermionic algebra in the mechanisms of breaking and restoration of chiral symmetry in the Nambu-Jona-Lasinio model. This model was chosen because it is an effective model for QCD which shows with reasonable facility one of its main features, the dynamical breaking of chiral symmetry and the generation of a dynamical mass for the quarks. The work can be divided essentialy in three parts. The first consists in a initial study where the deformation was implemented directly in the gap equation of the NJL model through a defor- med calculation of the condensates. In second part, the same deformation procedure was applied in the Hamiltonian of the model allowing their effects to be propagated in the calcula- tions till a new gap equation. A natural extension of the work is a study of the deformed model at finite temperature, where the coexistence of temperature and algebric deformation can be investigated. This study is the third part of the work.

No presente trabalho construímos o potencial nucleon-nucleon devido à troca de dois píons dentro do contexto relativístico da teoria de perturbação quiral, formulada por Becher e Leutwyler. No estudo do espalhamento píon-nucleon, eles desenvolveram um método que exibe a regra de contagem de potências, mantendo a invariância relativística. Os autores também chamam a atenção para um problema presente na formulação de bário pesado, de que sua série quiral não converge na região de baixa energia em torno de t=4µ2, onde µ é a massa do píon. Nós mostramos que este problema é bastante relevante para o potencial nucleon-nucleon, principalmente pelo fato dessa região de energia determinar suas características assintóticas. A dinâmica da troca de dois píons na interação nucleon-nucleon é determinada pelas sub-amplitudes píon-nucleon. Partindo da sub-amplitude de Becher e Leutwyler, obtemos diagramas classificados em três famílias, de acordo com sua topologia e constantes de acoplamento envolvidas. Na definição do potencial subtraímos, da amplitude relativéstica, a iteração da troca de um píon, seguindo a prescrição de Blankenbecler e Sugar. O nosso potencial até a ordem q4 é expresso em termos de seis funções básicas, associadas a integrais de loop, calculadas relativisticamente. Ele mantém as propriedades assintóticas corretas, desde que as integrais básicas não sejam expandidas. Forçando tal expansão, com o objetivo de comparar com os resultados de Entem e Machleidt, observamos concordância na maioria dos termos. Algumas diferenças estão associadas à discrepância na relação de Goldberger-Treiman, indicadas por GT, e dois termos, a contribuições de dois loops. As demais, muito provavelmente estão relacionadas à iteração da troca de um píon. No espaço de configuração, comparamos os nossos resultados com a parte de médio alcance de duas versões do potencial de Argonne, AV14 e AV18. Observamso uma boa concordância apenas para o potencial central isoescalar, o canal mais importante para a fenomenologia. Para as demais componentes, temos discrepâncias inclusive entre as versões AV14 e Av18. Com base na classificação da dinâmica em três famílias e analisando suas contribuições para cada componente, apresentamos uma proposta de como evitar ambiguidades desse tipo na construção de potenciais fenomenológicos. / This work is devoted to the construction of a two-pion Exchange nucleon-nucleon potential in the framework of the relativist chiral perturbation theory, formulated by Becher and Leutwyler. In their study of pion-nucleon scattering they developed a method to regain the Power counting rules while keeping Lorentz invariance. These authors also Drew attention to a problem present in the heavy baryon formulation, that is chiral serie does not converge in the low-energy region around t=4µ2, where µ is the pions mass. We have shown that this problem is rather relevant to nucleon-nucleon potential, mainly due to the fact that this range of energy determines its asymptotic properties. The dynamics of the two-pion Exchange nucleon-nucleon interaction is determined by pion-nucleon sub-amplitudes. Starting from Becher and Letwylers sub-amplitude, we obtain diagrams classified in three families, according to their topology and the coupling constants involved. In the definition of the potential we substract, from the relativist amplitude, the iteration o fone-pion Exchange, following the prescription of Blankenbecler and Sugar. Our potential up to order q4 is expressed in terms of six basic functions associated to relativistic loop integrals. It keeps the correct asymptotic properties, as long as we do not expand the basic integrals. Forcing such na expansio, in order to compare it with the results from Entem and Machleidt, we observe na agreement in the majority o terms. Some differrences are associated to the Goldberg-Treiman discrepancy, indicated by GT, and two terms come from two loop calculations. The remaining ones are probably related to the prescription adopted for the iteration o fone-pion exchange. In configuration space we compare our results with the médium-range component of two versions of the Argonne potential, AV14 and AV18. We obtain agreement only for the central isoscalar potential, the most important to phenomenology. Regarding other channels, we observe discrepancies even between AV14 and AV18. Based on the classification of the dynamics in three families and analysing their contributions to each component, we propose a way to overcome such ambiguities in the construction of phenomenological potentials.

O capítulo 1 descreve o estudo da biorredução do grupo carbonílico de cetoazidas e β-ceto-1,2,3-triazois para a produção de β-hidroxi-1,2,3-triazois enantiomericamente puros ou enriquecidos. Cinco linhagens de fungos de origem marinha foram avaliadas para a redução da 2-azido-1-feniletanona 1 e duas linhagens, A. sydowii CBMAI 935 e M. racemosus CBMAI 847, foram selecionadas também para a biorredução das 2-azido-1-feniletanonas 2-4 para a produção dos (R)- e (S)-2-azido-1-feniletanois 2a-4a. Os azidoálcoois enantiomericamente enriquecidos obtidos 1a-4a das reações biocatalíticas foram empregados como material de partida para a síntese dos β-hidroxi-1,2,3-triazois 7a-10a enantiomericamente enriquecidos através da click reaction entre a azida terminal e o alcino, fenilacetileno. Uma segunda abordagem para a obtenção de β-hidroxi-1,2,3-triazois enantiomericamente enriquecidos foi o estudo da biorredução de β-ceto-1,2,3-triazois, que são cetonas contendo dois substituintes volumosos. Uma triagem inicial para a biorredução do β-ceto-1,2,3-triazol 7 foi realizada com seis linhagens de fungos de origem marinha, na qual a linhagem do fungo P. citrinum CBMAI 1186 foi selecionada para estudos de otimização da reação biocatalítica. Estudos com variação do meio reacional, utilização de co-solvente e efeito do pH mostraram que as condições ótimas de reação foram utilizando-se tampão fosfato (Na2HPO4/KH2PO4, 0,07 M) em pH 5 e metanol 5% (v/v) como co-solvente. O fungo P. citrinum CBMAI 1186 foi empregado na biorredução dos β-ceto-1,2,3-triazois 8-12 com excelentes resultados de rendimento e seletividade para a produção dos (S)-β-hidroxi-1,2,3-triazois 8a-12a. O Capítulo 2 apresenta a síntese multienzimática da diidropinidina, um alcaloide de origem natural. A nonano-2,6-diona utilizada como material de partida foi obtida através da descarboxilação do dicetoéster, 2-butiril-5-oxo-hexanoato de etila. Estudos para a otimização tanto da síntese do dicetoéster quanto da etapa de descarboxilação foram realizados. Condições ótimas de produção do 2-butiril-5-oxo-hexanoato de etila foram obtidas através da reação da but-3-em-2-ona com o 3-oxo-hexanoato de metila catalisada por CeCl3/NaI. A descarboxilação do dicetoéster foi avaliada através do método de Krapcho empregando-se sais de cloro e água em altas temperaturas, entretanto, a elevada formação de subprodutos estimulou a busca por uma diferente metodologia para a obtenção da nonano-2,6-diona. Foram avaliadas diferentes lipases e esterases para a hidrólise enzimática do dicetoéster seguida por descarboxilação por HCl, na qual a esterase de fígado de porco foi selecionada e promoveu a hidrólise de até 1,6 M de dicetoéster para a produção da nonano-2,6-diona. Diferentes transaminases (TAs) foram estudadas para a aminação redutiva assimétrica da nonano-2,6-diona e duas linhagens foram selecionadas para a produção da (R)- e (S)-2-metil-6-propil-2,3,4,5-tetra-hidropiridina, as TAs de Arthrobacter sp. e Arthrobacter citreus, respectivamente empregando-se isopropilamina como amino doador. As (R)- e (S)-2-metil-6-propil-2,3,4,5-tetra-hidropiridina foram avaliadas pela redução assimétrica para a síntese da diidropinidina por imina redutases (IREDs) e duas linhagens foram selecionadas, a IRED de Mesorhizobium sp. e Norcardiopsis alba, respectivamente. TAs e IREDs foram acopladas em um sistema one-pot multienzimático utilizando como material de partida a nonano2,6-diona (100 mM) para a obtenção dos isômeros cis da diidropinidina com excelentes excessos diastereoisoméricos. / The Chapter 1 describes the bioreduction of the carbonyl group of ketoazides and β-keto-1,2,3-triazoles to produce enantiomerically pure or enriched β-hydroxy-1,2,3-triazoles. Five marine-derived fungi strains were screened to perform the reduction of 2-azido-1-phenylethanone 1. The strains from A.sydowii CBMAI 935 and M. racemosus CBMAI 847 were selected for the bioreduction of the 2-azido-1-phenylethanones 2-4 to yield the (R)- and (S)-2-azido-1-phenylethanols 2a-4a. The enantiomerically enriched azidoalcohols 1a-4a obtained from biocatalytical reactions were used as starting materials for the synthesis of enantiomerically enriched β-hydroxy-1,2,3-triazoles 7a-10a through the click reaction between the terminal azide and phenylacetylene. A second approach for obtaining enantiomerically enriched β-hydroxy-1,2,3-triazoles was the bioreduction of β-keto-1,2,3-triazoles, which are ketones with two bulky substituents. The screening for the bioreduction of the β-keto-1,2,3-triazol 7 was performed with six marine-derived fungi strains and P. citrinum CBMAI 1186 was selected for the optimization studies for the biocatalytic reduction of β-keto-1,2,3-triazoles 8-12.Studies about the composition of reaction medium, use of cosolvent and pH effect showed that the optimal conditions was in phosphate buffer (Na2HPO4/KH2PO4, 0.07 M) at pH 5 and methanol 5% (v/v) as cosolvent. P. citrinum CBMAI 1186 was applied to the bioreduction of β-keto-1,2,3-triazoles 8-12 and good yields and selectivities were obtained for the (S)-β-hydroxy-1,2,3-triazoles 8a-12a. The Chapter 2 describes the multienzymatic synthesis of dihydropinidine, a natural alkaloid. The nonane-2,6-dione used as starting material was obtained through the reduction of the diketoester, methyl butyryl-5-oxohexanoate, and the optimization studies for both diketoester synthesis and decarboxylation reaction were performed. Optimal conditions for the synthesis of methyl butyryl-5-oxohexanoate were obtained by the reaction between but-3-en-2-one and 3-oxohexanoate catalyzed by CeCl3/NaI. The diketoester decarboxylation step was evaluated by the Krapcho method using chlorine and water at high temperatures. However, because of the production of side products by this method, a different procedure for the synthesis of nonane-2,6-dione was studied. Different enzymes (lipases and esterases) were evaluated for the diketoester hydrolysis followed by decarboxylation by HCl. The porcine liver esterase was selected to promote the diketoester hydrolysis up to 1.6 M, yielding nonane-2,6-dione. Different transaminases (TAs) were applied to the asymmetric reductive amination of the nonane-2,6-dione and TAs from Arthrobacter sp. e Arthrobacter citreus were selected for the production of (R)- and (S)-2-methyl-6-propyl-2,3,4,5-tetrahydropyridine, respectively, using isopropylamine as the amine donor. The asymmetric reduction of (R)- and (S)-2-methyl-6-propyl-2,3,4,5-tetrahydropyridine by imine reductases (IREDs) was evaluated and the IREDs from Mesorhizobium sp. and Norcardiopsis alba were selected. TAs and IREDs were coupled in multienzymatic one-pot system using nonane-2,6-dione (100 mM) as starting material for the syntheses of cis isomers of dihydropinidine in excellent diastereoisomeric excess.

Neste trabalho, avaliou-se o potencial do uso de oxidantes quirais em oxidações enantiosseletivas de compostos orgânicos de boro. É de conhecimento geral que compostos orgânicos de boro, especialmente ésteres e ácidos borônicos são facilmente oxidados por hidroperóxidos em meio básico. No entanto, são escassos na literatura exemplos destas reações de modo enantiosseletivo. A fim de realizar as reações mencionadas, sintetizou-se os hidroperóxidos quirais TADOOH ({(4R,5R)-5-[(hidroperoxidifenil)metil]-2,2-dimetil-1,3-dioxolan-4il}difenilmetanol) e o hidroperóxido quiral derivado de carboidrato, 2,3-dideoxi1-O-oxidanil-4,6-di-O-pivaloil-α-D-eritro-hex-2-enopiranose (di-O-PivOOH). Estes compostos apresentaram resultados interessantes na literatura em oxidações enantiosseletiva de sulfetos orgânicos, em epoxidações de alcenos e em oxidações de Baeyer-Villiger. Inicialmente o potencial oxidativo de ambos hidroperóxidos, bem como a seletividade destes, foi avaliado frente a diversos ésteres borônicos, sendo que somente o TADOOH apresentou resultados promissores. (Ver esquema no PDF) Observou-se uma melhor seletividade do TADOOH frente a ésteres borônicos que possuíam grupos carbonílicos em sua estrutura. Ao submeter o β-boronil-éster, 3-fenil-3-(4,4,5,5-tetrametil-1,3,2-dioxaborolan-2-il)propanoato de etila, à oxidação com o TADOOH em THF utilizando NaOH como base, a -30°C por 1 hora, obteve-se o respectivo álcool com 40% de e.e. Cálculos de DFT para o estado de transição na oxidação dos ésteres borônicos com o TADOOH foram realizados em colaboração com o grupo do Prof. Dr. Ataualpa Albert Carmo Braga. Estes cálculos demonstraram que o estado de transição é estabilizado por uma ligação de hidrogênio não clássica entre o oxigênio da carbonila e umas das ligações C-H dos grupos fenila do TADOOH. Além dos estudos relatados, a reconhecida metodologia de Sharpless na epoxidação assimétrica de alcoóis alílicos foi adaptada para a oxidação enantiosseletiva de ésteres borônicos. Ao trocar o ligante derivado de éster tártarico, normalmente utilizado nas epoxidações de Sharpless, por (-)-efedrina observou-se uma moderada seletividade deste sistema frente ao pinacol l-fenietilboronato. Investigações mais detalhadas demonstraram que a presença do Ti(IV) não era necessária, sendo que a (-)efedrina era a responsável pela ativação e indução quiral nesta reação. / In this work, it was investigated the potential use of chiral oxidants in organic boron compound oxidation. It is known in the literature, that organic boron compounds can be easily oxidized by hydroperoxides. However, an enantioselective approach in literature is scarce. In order to perform these reactions, hydroperoxide TADOOH ({(4R,5R)-5[(hydroperoxydiphenyl)methyl]-2,2-dimethyl-l,3-dioxolan-4-yl}diphenylmethanol) and carbohydrate derived hydroperoxide, 2,3-dideoxy-1-O-oxidanyl-4,6-di-O-pivaloyl-α-D-erythro-hex-2-enopyranose (di-O-PivOOH), have been synthesized. These compounds showed interesting results in several enantioselective oxidations, as like, organic sulfides oxidation, alkenes epoxidation and Baeyer-Villiger oxidations. The oxidative potential of both hydroperoxides, as well as their selectivity, were evaluated against several boronic esters. Only TADOOH has shown promissing results for further studies. (See Scheme on PDF). Boronic esters containing a carbonyl moiety showed better selectivities with TADOOH, for example, the reaction of β-boronyl-ester, ethyl 3-phenyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)propanoate, gave the correponding alcohol with 40% e.e. DFT calculations for the transition state in the oxidation of the boronic esters with TADOOH were carried out in collaboration with the group of Prof. Dr. Ataualpa Albert Carmo Braga. These calculations have shown that the transition state is stabilized by a non-classical hydrogen bond between the carbonyl oxygen and one of the C-H bonds of the TADOOH phenyl groups. In addition to the studies, the well-known Sharpless protocol for asymmetric epoxidation of allylic alcohols was adapted in the enantioselective oxidation of boronic esters. By replacing the tartaric ester-derived, commonly used in the Sharpless experiments, for (-)-ephedrine moderate selectivity was observed with pinacol 1-phenylethyl boronate. Further investigations showed that the presence of Ti (IV) was not necessary, and (-)-ephedrine was responsible for the activation and chiral induction in this reaction.

A teoria de perturba ca o quiral (ChPT) e aceita, atualmente, como a teoria efetiva da cromodinamica quantica (QCD) para baixas energias. Ela foi colocada na sua versa o moderna com os artigos de Gasser e Leutwyler, na primeira metade da d ecada de 80 e, durante os 25 anos que se seguiram, ocorreu um aumento considera vel da variedade de fenomenos por ela descritos, sempre acompanhando a precisa o cres- cente dos resultados experimentais. Os trabalhos que apresentamos nesta tese de doutorado se inserem neste contexto e envolvem duas partes, ambas relacionadas a` determina c ao de alguns dos parametros que compo em a lagrangiana da ChPT. Por ser uma teoria efetiva, tais constantes s o podem ser fixadas por experimentos, modelos ou por c alculos da QCD na rede. Em um dos trabalhos, discutimos a cons- tante de decaimento do p on, F, e os efeitos decorrentes do acr escimo de intera co es eletromagn eticas a` ChPT. N os argumentamos que as incertezas estimadas para o valor mais aceito de F podem estar subestimadas. Mostramos, tamb em, que na o se pode determinar esta constante na presen ca das intera co es eletromagn eticas, pois a grandeza de onde ela e extra da adquire uma dependencia no calibre utilizado no ca lculo e tem suas propriedades alteradas drasticamente. No outro trabalho, abor- damos os fatores de forma escalares dos m esons pseudoescalares em tres sabores. A partir dos resultados obtidos com a ChPT e do uso de um modelo que trata dos fatores de forma no espa co das posi co es, conseguimos escreve-los em termos ape- nas das constantes presentes na lagrangiana em ordem dominante da ChPT, F e as massas dos m esons pseudoescalares. No s determinamos, tamb em, os respectivos raios quadra ticos m edios e, comparando-os com os calculados com a ChPT, obtive- mos as LECs L4(mu) = -0,26 · 10^-3 e L5(mu) = 0,85 · 10^-3, para mu = 770 MeV. Esses valores sa o compat veis com as principais estimativas vindas da ChPT. / At present, chiral perturbation theory (ChPT) is considered the effective theory of quantum chromodynamics (QCD) at low energies. It was established in its modern version by the papers of Gasser and Leutwyler written in the first half of the 80s. For the last 25 years, there has been considerable increase in the number of phe- nomena described by ChPT, always following the growing precision of experiments. The two works we present in this Ph.D. thesis are related to ChPT and discuss the determination of some of the parameters that appear in the ChPT lagrangian. As ChPT is an effective theory, such constants can only be fixed by experiments, models or calculations in the lattice. In the first presented work, we discuss the pion decay constant, F, and how it is changed by the inclusion of electromagne- tic interactions. We argue that the uncertainty of the most accepted value of F might be underestimated. We also show that we cannot determine this constant in the presence of electromagnetic interactions because the function from which it is extracted acquires a gauge dependence and the functions properties drastically change. In the other work, we deal with pseudoscalar meson scalar form factor in three flavors. We manage to write the form factors only in terms of constants present in ChPT lagrangian at leading order, F and masses of pseudoscalar mesons, using ChPT results and the model that deals with form factors in coordinate space. We also determine the respective square radii and, comparing these to those calculated using ChPT, we have obtained L4(mu) = -0.26 · 10^-3 and L5(mu) = 0.85 · 10^-3, for mu = 770 MeV. These values are compatible with the main estimates evaluated with ChPT.