Acquisition of X-ray crystallographic data is always accompanied by structural degradation owing to the absorption of energy. The application of high-fluency X-ray sources to large biomolecules has increased the importance of finding ways to curtail the onset of X-ray-induced damage. A significant effort has been under way with the aim of identifying strategies for protecting protein structure. A comprehensive model is presented that has the potential to explain, both qualitatively and quantitatively, the structural changes induced in crystalline protein at 100 K. The first step is to consider the qualitative question: what are the radiation-induced intermediates and expected end products? The aim of this paper is to assist in optimizing these strategies through a fundamental understanding of radiation physics and chemistry, with additional insight provided by theoretical calculations performed on the many schemes presented.

No description available.

The development of chiral organometallics for asymmetric synthesis is a topic of significant research in the recent past. The most studied in this class are the chiral organolithium reagents with many reported examples. The primary focus of our research is the development of C_α-chiral Grignard reagents, where the metal bearing α-carbon is the sole source of chirality. Examples of such Grignard reagents are rare owing to the problems associated with their synthesis, and their low configurational stability. We have studied these problems in three different modules of this project. Reactions of 1-magnesio-2,2-diphenyl-cyclopropylcarbonitrile with carbon electrophiles are first attempted in order to expand the utility of this configurationally stable C_α-chiral Grignard reagent in asymmetric synthesis. This reagent has been shown to be non-reactive towards carbon electrophiles at low temperatures. Consequently, we attempt to enhance the reactivity of this compound through two different approaches, Lewis-base activation and the "ate-complex" generation. The Magnesium/Halogen (Mg/X) exchange reactions have been shown to be extremely useful in the synthesis of complex Aryl, alkenyl (sp²) and alkynyl (sp) Grignard reagents. Examples of Mg/X exchange reactions of Alkyl (sp³) halides are, however, rare. Even more rare are such examples with secondary and tertiary alkyl halides, justifying the relative paucity of chiral Grignard reagents. In this module of our project, we study the Mg/X exchange reactions on secondary alkyl halides possessing a γ-hydroxyl group, as an internal activator for such Mg/X exchange reactions. Enantiomerization pathways of chiral organolithium compounds have been widely studied. However, few such studies have been performed on chiral Grignard reagents. In this module of the project, we studied the solvent assisted enantiomerization mechanism of the C_α-chiral 1-magnesio-2,2-diphenyl-cyclopropylcarbonitrile. Rate constant for the enantiomerization of this compound was measured in three different ethereal solvents to study the effect of solvent on the configurational stability. Finally, the order of the enantiomerization process with respect to [Et₂O] was studied in order to predict the mechanism of this process in Et₂O solvent. Our kinetic studies on the enantiomerization process provided us with a definitive picture for the enantiomerization of the C_α-chiral 1-magnesio-2,2-diphenyl-cyclopropylcarbonitrile, where solvation of the Grignard reagent preceded an ion-pair separation step which eventually lead to enantiomerization of the Grignard species. However, the precise structure of all the involved solvated intermediates could not be determined as kinetics was not able to distinguish between these intermediates. We next performed computational calculations to study the effect of solvation on the analogous 1-magnesio-cyclopropylcarbonitrile in order to address the unanswered questions from our kinetic studies. / Ph. D.

Com o aumento da consciência global sobre os riscos do Aquecimento do Planeta e de suas possíveis causas ficou claro que é necessário desenvolver ou adaptar processos industriais de maneira a aproveitar dejetos como o CO2. Dentre as formas de se aproveitar o CO2, destaca-se a ciclo-adição aos epóxidos, com a formação de ciclocarbonatos. A reação é tecnologicamente interessante, pois ciclocarbonatos possuem diversas aplicações como solventes polares apróticos, eletrólitos e matéria prima para compostos como purinas, carbamatos, glicóis, policarbonato e outros. Para que a reação ocorra em tempo e condições viáveis, há a necessidade de se trabalhar com catalisadores. Foram reportados muitos catalisadores ao longo dos anos. Dentre os catalisadores mais comumente utilizados, destacam-se os sais orgânicos. Porém o estudo sobre modelos cinéticos e mecanismo de reação ainda carecem de mais atenção. Desta forma este trabalho propõe-se a estudar esta parte, através de experimentos cinéticos, modelos teóricos e cálculos de química quântica. Para isto escolheu-se estudar a ação catalítica do brometo de 1-propil-4-azo-1-azôniobiciclo[2,2,2]octano (P-DABCO) frente a um catalisador bem descrito na literatura, o brometo de tetrapropilamônio (TPA). / Nowadays mankind are becoming more aware about Global Warming risks and its possible causes. With that in mind, it is necessary to develop or to adapt industrial processes to use some wastes like CO2. One of the best strategies to utilize CO2 is to convert it to cyclic carbonate through cyclic addition reaction to epoxides. This reaction is important because cyclic carbonates have other useful applications. For example, they can be used as polar aprotic solvents, electrolytes and as starting material for other compounds like purine, carbamates, glycols, polycarbonate, among others. However, the cyclic addition reaction must be catalyzed so as to get the desired product in short possible time and under soft conditions. Many catalysts have been reported in the literature that can be used for the cyclic addition reaction, with the organic salts being very common ones. Most of these reports focus on the efficiency of the catalyst and little attention has been paid to the reaction kinetics models and reaction mechanisms. Thus, we intend to study this part. For this purpose, we will do kinetics experiments, theoretical models and quantum chemistry calculation. The 1-alkyl-4-aza-1-azaniabicyclo[2.2.2]octyl bromide was chosen to this work and will be compared with tetrapropylammonium bromide that is known in the literature.

Com o aumento da consciência global sobre os riscos do Aquecimento do Planeta e de suas possíveis causas ficou claro que é necessário desenvolver ou adaptar processos industriais de maneira a aproveitar dejetos como o CO2. Dentre as formas de se aproveitar o CO2, destaca-se a ciclo-adição aos epóxidos, com a formação de ciclocarbonatos. A reação é tecnologicamente interessante, pois ciclocarbonatos possuem diversas aplicações como solventes polares apróticos, eletrólitos e matéria prima para compostos como purinas, carbamatos, glicóis, policarbonato e outros. Para que a reação ocorra em tempo e condições viáveis, há a necessidade de se trabalhar com catalisadores. Foram reportados muitos catalisadores ao longo dos anos. Dentre os catalisadores mais comumente utilizados, destacam-se os sais orgânicos. Porém o estudo sobre modelos cinéticos e mecanismo de reação ainda carecem de mais atenção. Desta forma este trabalho propõe-se a estudar esta parte, através de experimentos cinéticos, modelos teóricos e cálculos de química quântica. Para isto escolheu-se estudar a ação catalítica do brometo de 1-propil-4-azo-1-azôniobiciclo[2,2,2]octano (P-DABCO) frente a um catalisador bem descrito na literatura, o brometo de tetrapropilamônio (TPA). / Nowadays mankind are becoming more aware about Global Warming risks and its possible causes. With that in mind, it is necessary to develop or to adapt industrial processes to use some wastes like CO2. One of the best strategies to utilize CO2 is to convert it to cyclic carbonate through cyclic addition reaction to epoxides. This reaction is important because cyclic carbonates have other useful applications. For example, they can be used as polar aprotic solvents, electrolytes and as starting material for other compounds like purine, carbamates, glycols, polycarbonate, among others. However, the cyclic addition reaction must be catalyzed so as to get the desired product in short possible time and under soft conditions. Many catalysts have been reported in the literature that can be used for the cyclic addition reaction, with the organic salts being very common ones. Most of these reports focus on the efficiency of the catalyst and little attention has been paid to the reaction kinetics models and reaction mechanisms. Thus, we intend to study this part. For this purpose, we will do kinetics experiments, theoretical models and quantum chemistry calculation. The 1-alkyl-4-aza-1-azaniabicyclo[2.2.2]octyl bromide was chosen to this work and will be compared with tetrapropylammonium bromide that is known in the literature.

The thesis describes the realization of an asymmetric [2,3]-sigmatropic rearrangement of achiral allylic amines. It is divided into two parts; the first part deals with the development of a Lewis acid-mediated [2,3]-sigmatropic rearrangement and the second the asymmetric version thereof. Quaternization of an -amino amide with various Lewis acids established BBr3 and BF3 to be the most appropriate ones. Various allylic amines were subsequently rearranged into the corresponding homoallylic amines in good to excellent syn-diastereoselectivities, revealing the endo-transition state to be the preferred pathway. The structures of the intermediate Lewis acid-amine complexes were confirmed by NMR spectroscopy studies and DFT calculations. Based on this investigation a chiral diazaborolidine was chosen as Lewis acid and was shown to efficiently promote the asymmetric [2,3]-sigmatropic rearrangement furnishing homoallylic amines in good yields and excellent enantiomeric excesses. In contrast to the achiral rearrangement mediated by BBr3 and BF3, the asymmetric version gave the opposite major diastereomer, revealing a preference for the exo-transition state in the asymmetric rearrangement. To account for the observed selectivities, a kinetic and thermodynamic pathway was presented. On the basis of a deuterium exchange experiment on a rearranged Lewis acid-amine complex and an NMR spectroscopic investigation, the kinetic pathway was shown to be favored. / QC 20100927

In the recent studies thiocyanate-containing metal complexes are considered to be the most investigated systems. Such complexes exhibit specific properties which could be applied in various fields such as catalysis, photochemistry, biochemistry, pharmacology and etc. The complexes of mercury(II) and iron(III) thiocyanates are of interest since they are widely applied for analysis in the clinical or industrial laboratories. As a result these complexes received great attention, due to the fascinating properties in designing new materials with inorganic and organic ligands. Dealing with such complex system, accurate prediction of the synthesized compound properties is challenging. For this reason, researchers analyze how the replacement of certain group, modification, molar ratio of the mixed ligands and etc. may influence the structure and properties of the obtained complex. Molecular structure, vibrational and electronic spectra of aqueous mercury(II) thiocyanate and iron(III) monoisothiocyanate solutions (at the pH ~ 2) were analyzed in the dissertation by means of Raman and UV-VIS spectroscopies and quantum chemical calculations. The structure, coordination number and vibrational assignments of the titled complexes were determined. The influence of different solvation models upon spectral properties was estimated. The excited state analysis of iron(III) monoisothiocyanate was performed. / Metalų tiocianatų chemija yra ypatingai sparčiai besivystanti tyrimų kryptis. Dėl specifinių metalų tiocianatų savybių šie junginiai plačiai taikomi katalizinėje chemijoje, biochemijoje, farmakologijoje, fotochemijoje ir pan. Vieni iš plačiausiai nagrinėjamų pereinamųjų metalų tiocianatų kompleksų yra geležies ir gyvsidabrio tiocianatai. Pastaruoju metu mokslininkai bando susintetinti kompleksinius geležies ir gyvsidabrio tiocianatų junginius, turinčius neorganinį ir organinį ligandus, kurie pasižymi specifinėmis savybėmis tokiomis kaip: liuminescencija, magnetizmas, katalizinis aktyvumas ir pan. Tačiau, siekiant susintetinti junginius su norimomis fizikinėmis ir cheminėmis savybėmis, reikalingos žinios apie kompleksų struktūras, kompleksavimo ypatybes ir visą tai įtakojančius veiksnius molekuliniame lygmenyje. Disertacijoje analizuota tirpių gyvsidabrio(II) tiocianatų ir geležies(III) monoizotiocianato kompleksų (esant pH ~ 2) molekulinė struktūra, virpesiniai ir elektroniniai spektrai taikant Ramano ir UV-RŠ spektroskopines analizes bei kvantinius skaičiavimus. Nustatyti kompleksų koordinacijos skaičiai ir struktūros, atlikti funkcinių grupių signalų priskyrimai, įvertinta solvatacijos įtaka kompleksų spektrinėms savybėms ir išanalizuoti geležies(III) monoizotiocianato komplekso elektroniniai perėjimai sužadintoje būsenoje.

Polymorphism, defined as the ability of a molecule (or a set of molecules) to adopt several packing arrangements, became, in the last decades, a field of research on its own. Among other advantages of studying polymorphic systems, one can cite the study of the influence of molecular packing on solid-state properties, a better understanding of nucleation and crystal growth mechanisms. These advantages became relevant due to their impacts on the control of bioavailability and processes in pharmaceutical industry. In the present work we study the polymorphism of a pharmaceutical substance, the modafinil, which is the active pharmaceutical ingredient (API) of the ProvigilÂ. Modafinil, whose chemical name and structural formula are, respectively, 2-[(diphenylmethyl)sulfinyl]acetamide and C15H15NO2S, is indicated in the treatment of narcolepsy, specifically the excessive daytime sleepiness (EDS), which is a narcolepsy side effect. Up to now, seven polymorphic forms of modafinil have been observed and the polymorphic forms I and III are the most stable ones. The determination of the crystalline structures of the forms I and III showed that there are two independent molecules, which are enantiomers, in each one of these polymorphs. Besides, modafinil has been crystallized in the forms R and S obtained after the separation of the enantiomers. DFT calculations were performed to investigate the conformational stability of the molecules of modafinil. The main torsions of the molecules were scanned in order to identify the stable conformations, which were compared with independent ones obtained from the crystalline structures determined experimentally. For each calculated conformation, we also calculated the vibrational spectra. These theoretical results were compared with the Raman spectra of the polymorph III of modafinil. In such a way, the main features of the vibrational spectra that allow the polymorph discrimination were correlated with molecular groups associated to these vibrational modes providing an insight into the intra- and intermolecular interaction associated to the polymorphism of modafinil. / O polimorfismo, definido como a habilidade de uma molÃcula (ou um conjunto de molÃculas) de adotar diferentes arranjos estruturais, tornou-se, nas Ãltimas dÃcadas, um campo de pesquisa bastante intenso. Dentre outras vantagens de estudar sistemas polimÃrficos, podemos destacar o estudo da influÃncia do empacotamento molecular nas propriedades de estado sÃlido, um melhor entendimento dos mecanismos de crescimento dos cristais. Estas caracterÃsticas ganharam relevÃncia devido a seu impacto no controle da biodisponibilidade e dos processos da indÃstria farmacÃutica. Neste trabalho, focamos nosso estudo no polimorfismo de uma substÃncia farmacÃutica, o modafinil, que à o ingrediente ativo no ProvigilÂ. O modafinil, cuja nomenclatura quÃmica e fÃrmula molecular sÃo, respectivamente, 2-[(difenilmetil)sulfinil]acetamida e C15H15NO2S, à indicado para o tratamento da narcolepsia, mais especificamente o "excesso de sono diurno", que à uma das conseqÃÃncias desta doenÃa. Atà agora, sete formas polimÃrficas do modafinil foram observadas, sendo as formas I e III as mais estÃveis. A determinaÃÃo da estrutura cristalina das formas I e III mostra que existem duas molÃculas independentes em cada um desses polimorfos, as quais sÃo enantiÃmeras. AlÃm disso, o modafinil tambÃm foi cristalizado nas formas R e S obtidas apÃs a separaÃÃo dos enantiÃmeros. Neste trabalho usamos cÃlculos de DFT para investigar a estabilidade conformacional do modafinil. As principais torÃÃes das molÃculas foram varridas com o objetivo de identificar as conformaÃÃes estÃveis, que foram entÃo comparadas com as molÃculas independentes observadas nas estruturas cristalinas determinadas experimentalmente. Para cada conformaÃÃo calculada, tambÃm determinamos o espectro vibracional. Esses resultados teÃricos foram comparados com o espectro Raman do polimorfo III do modafinil. As principais caracterÃsticas do espectro vibracional, que permitem a caracterizaÃÃo do polimorfo, foram relacionadas com os grupos moleculares associados aos modos normais de vibraÃÃo, fornecendo informaÃÃes sobre as interaÃÃes intra- e intermoleculares associadas com o polimorfismo do modafinil.

Les triarylbismuths sont des réactifs organométalliques d’un intérêt croissant en synthèse organique, pour leur aptitude à transférer leurs trois groupements aryles dans les réactions de couplage croisé C-C pallado-catalysées. Ces réactifs essentiellement non toxiques et « économiques en atomes » sont attrayants dans le cadre d’une chimie plus respectueuse de l’environnement, et présentent des applications en chimie pharmaceutique et en science des matériaux. Cependant, leur développement est ralenti par le manque de connaissances théoriques à leur sujet. Cette thèse vise alors à comprendre la réactivité de ces espèces en confrontant les données expérimentales avec celles obtenues à travers une étude théorique fondamentale (propriétés structurelles, spectroscopiques, thermodynamiques et cinétiques) résultant de calculs DFT. Le but ultime est de prévoir de nouvelles réactivités et sélectivités. Un premier volet se rapporte à une étude comparative de relation structure-propriétés sur des composés incluant un pnictogène comme atome central, tel que le bismuth, et sur différents organobismuths. Les données expérimentales existantes (cristallographiques, RMN, IR) ont été comparées aux résultats théoriques (structures, énergies, modes de vibration, indices de réactivité, etc.). Une fois les propriétés intrinsèques de ces composés mises en évidence et la méthode DFT validée, une nouvelle étude de relation structure-réactivité a été entreprise. Dans ce deuxième volet, nous avons validé le mécanisme des réactions de couplage croisé impliquant des triarylbismuths catalysées par le palladium. Les trois étapes principales du cycle catalytique ont été examinées, à savoir l'addition oxydante, la transmetallation et l'élimination réductrice, et validées en caractérisant les différents intermédiaires et états de transition. La deuxième étape de transmetallation impliquant les triarylbismuths a également fait l'objet d'une étude approfondie. En particulier, la transférabilité des trois groupements aryles et l'influence des substituants (effets électroniques et stériques) sur les barrières de transfert ont été évaluées. Enfin, la réactivité des triarylbismuths a été comparée avec celle d’autres organométalliques afin de développer de nouvelles voies de synthèse / Triarylbismuths are organometallic reagents of growing interest for organic synthesis, for their ability to transfer the three aryl moieties in C-C Pd-catalysed cross-coupling reactions. These essentially non-toxic, atom efficient reactants are attractive in the context of environment-friendly chemistry and have applications in pharmaceutical chemistry and in material science. However, their development is hampered by lack of theoretical understanding. This thesis aims to explore the reactivity of these species by comparing the experimental data to fundamental theoretical studies (structural, spectroscopic, thermodynamic and kinetic properties) resulting from DFT calculations. The ultimate goal is to predict new reactivities and selectivities. A first approach consists in a comparative study on the relation between structure and properties in compounds having a pnictogen central atom like bismuth, and in different organobismuths. The existing experimental data (crystallographic, NMR, IR) were compared to the results of theoretical calculations (structures, energies, vibrational modes, reactivity parameters, etc.). After highlighting the intrinsic properties of these compounds and validating the DFT method, a new study was undertaken to elucidate the relations between structure and reactivity. This second investigation enabled us to validate the mechanism of the cross-coupling reaction involving triarylbismuths under palladium catalysis. The three major steps of the catalytic cycle have been examined, i.e. the oxidative addition, transmetallation and reductive elimination, and validated by characterizing the different intermediates and transition states. The second transmetalation step involving the triarylbismuths has also been deeply investigated. The transferability of the three aryl groups and the influence of the electronic and steric effects of the substituents on the energy barrier have been evaluated. Finally, the reactivity of triarylbismuths has been compared with that of other organometallics, to develop new synthetic approaches

The structural, electronic, energetic and optical properties of the compound Li2B4O7 containing the substitutional defects Cu or Ag were investigated by means of calculations of first principles at the Density Functional Theory level using the LAPW method implemented in the computer code Wien2k. The isolated Cu and Ag defects are considered in four charge states (q = -1, 0, +1, +2) with objective to simulate situations of the capture of an electron or a hole. In all cases, the atomic positions are computationally relaxed, Cu – O and Ag – O chemical bonds nature carefully analyzed and local structure around the defects determined. It is found that the defects vastly perturbs its neighborhood and the Cu and Ag themselves exhibit significant off-site dislocation from initial Li position in their Cu1+ and Ag1+ charge states, which becomes especially more pronounced for the Cu0 and Ag0 defects. Only the Cu2+ and Ag2+ centers stabilize at the substitutional Li site. Resulting defect formation energies demonstrate that the Cu1+, Cu0, Ag1+, and Ag0 centers are the most stable ones. Electronic structure calculations reveal that the Cu and Ag ions introduce their d- and s-states within the gap and their energies and occupation depend strongly on the charge state of the defect. Experimental optical absorption spectra are well reproduced by the Cu1+ and Ag1+ defects spectra, leading to the conclusion that in the as-grown material just Cu1+ and Ag1+ centers are formed. In the case of irradiated compound, present study predicts formation of the interstitial Cu0 defects, whose presence should significantly change the optical absorption and emission of the material, as well as demonstrates the presence of new absorption peaks associated with the interstitial Ag0 and substitutional Ag2+ centers, which reasonably describe the experimental spectrum. / As propriedades estruturais, eletrônicas, energéticas e ópticas do composto Li2B4O7 contendo os defeitos substitucionais Cu ou Ag foram investigadas por meio de cálculos de primeiros princípios ao nível da Teoria do Funcional da Densidade, utilizando-se o método LAPW implementado no código computacional Wien2k. Os efeitos de troca-correlação foram considerados usando-se o potencial modificado de Becke-Johnson (mBJ) e a aproximação do gradiente generalizado (GGA) na parametrização PBEsol. As células contendo os defeitos (Cu ou Ag) foram estudadas em quatro estados de carga diferentes (q = -1, 0, +1, +2) com o objetivo de simular situações de captura de elétrons ou de buracos. Em todos os casos, as posições atômicas foram relaxadas, a natureza das ligações Cu – O e Ag – O cuidadosamente analisada e as estruturas locais em torno dos defeitos determinadas. Verificou-se que os defeitos perturbam amplamente suas vizinhanças e que os centros Cu1+ e Ag1+ exibem um deslocamento significativo a partir da posição inicial do Li, que se torna ainda mais acentuado para os centros Cu0 e Ag0. Apenas os defeitos Cu2+ e Ag2+ se estabilizam no sítio substitucional do Li. Os resultados das energias de formação dos defeitos demonstraram que os centros Cu1+, Cu0, Ag1+ e Ag0 são os mais estáveis. Cálculos de estrutura eletrônica revelaram que as impurezas introduzem os estados d e s dentro do gap, cujas energias e ocupações dependem fortemente do estado de carga do defeito. Os espectros ópticos experimentais foram bem reproduzidos pelos espectros dos centros Cu1+ e Ag1+ calculados, levando-se à conclusão de que somente estes centros são formados no material não irradiado. Durante a irradiação do composto, o presente estudo prevê a formação dos centros intersticiais Cu0, fato que deve alterar significativamente a absorção e emissão óptica do material, bem como demonstra a presença de novos picos de absorção associados aos centros intersticiais Ag0 e substitucionais Ag2+, os quais descrevem razoavelmente bem o espectro experimental. / São Cristóvão, SE