Made available in DSpace on 2014-08-20T13:25:38Z (GMT). No. of bitstreams: 1 dissertacao_rosane_guidotti.pdf: 1652873 bytes, checksum: e165e27a1c291c18f1a683f1efc62a01 (MD5) Previous issue date: 2013-09-30 / Teaching and research activities in different areas of knowledge employ various chemicals substances, some of which are considered dangerous, offering potential risk to those who manipulate it or risk to the environment. The estimation of potential acidity (H + Al) in soils, made by SMP method uses two toxic reagents, p-nitrophenol and potassium chromate. To minimize toxic effect of these reagents, a new method called Sikora was proposed and tested in American soils, with positive results, which replaced them, respectively, by imidazole and the MES (2-N-morpholino ethanesulfonic acid monohydrate), not considered harmful. Sikora method has been tested in some Brazilian soils of Rio Grande do Sul State (RS) and from Central Brazil (Cerrado), and did not present a good correlation. For this reason, the Sikora method was modified and calibrated for these same soils and called Santa Maria buffer (TSM). This study aimed to evaluate the effectiveness of the original Sikora method and his version TSM in the estimation of the soil potential acidity in order to replace the SMP method calibrated for RS and Santa Catarina (SC) States, in a large group of soils, from RS and Mato Grosso (MT) States, with contrasting chemical and physical characteristics. The methods were tested using 110 soil samples from MT and 103 from RS, collected at 0-20 cm depth, in cultivated and uncultivated areas. The results were submitted to correlation analysis and descriptive statistics analysis. A second degree polynomial was adjusted to compare the potential acidity titrated with the pH values obtained with the three methods. Among methods, the higher accuracy in predicting the potential acidity was observed in the following order: SMP > TSM > Sikora, for both soils from RS State Southern and Planalto region as well for those of MT state. In RS state, the TSM method showed to be feasible to estimate potential acidity (H + Al) for soils of both regions, allowing the adoption of a single mathematical model. Only the SMP method presented universality in estimating potential acidity (H + Al) for soils of the two states, RS and MT. Sikora and TSM methods reproduced pH values obtained with SMP method for MT soils and therefore can be used for limestone recommendation. For RS State, the TSM method was more efficient than the Sikora method on the reproduction of soils pH values obtained with the SMP method, being the most suitable to replace SMP method in soil analysis laboratories and therefore to be used on limestone recommendation. / As atividades de ensino e pesquisa nas diversas áreas do conhecimento empregam várias substâncias químicas, sendo algumas consideradas perigosas, oferecendo risco potencial aqueles que as manipulam e ao meio ambiente. A estimativa da acidez potencial (H + Al) em solos, feita pelo método SMP, utiliza dois reagentes de caráter tóxico, o p-nitrofenol e o cromato de potássio. Para minimizar o efeito tóxico destes reagentes, foi proposto e testado com resultados positivos em solos americanos um método denominado Sikora, que os substituiu, respectivamente, pelo imidazol e pelo MES (ácido 2-N-morfolino etanosulfonico monohidratado), considerados menos tóxicos. No Brasil, o método Sikora foi testado em alguns solos do Estado do Rio Grande do Sul (RS) e do Cerrado. Como não apresentou uma boa correlação, o método foi modificado, calibrado para estes mesmos solos e denominado Tampão Santa Maria (TSM). O presente trabalho teve como objetivo avaliar a eficácia do método Sikora original e sua versão TSM na estimativa da acidez potencial num amplo grupo de solos, dos Estados do RS e do Mato Grosso (MT), com características químicas e físicas contrastantes, com vistas à substituição do método SMP calibrado para os Estados do RS e Santa Catarina (SC). Os métodos foram testados em 110 amostras de solos do MT e 103 amostras de solos dos RS, coletados na camada de 0-20 cm, em áreas cultivadas e não cultivadas. Os resultados foram submetidos a análises de correlação e estatística descritiva. Ajustou-se um polinômio de segundo grau para a comparação dos valores de pH obtidos com acidez potencial titulada e os três métodos. A maior acurácia na predição da acidez potencial foi observada na seguinte ordem entre os métodos avaliados: SMP>TSM>Sikora, tanto para solos das regiões Sul e Planalto do RS como para o Estado do MT. No RS, o método TSM mostrou-se viável em estimar acidez potencial (H + Al) para os solos das duas regiões do RS, possibilitando a adoção de um modelo matemático único. Apenas o método SMP apresentou universalidade na estimativa da acidez potencial (H + Al) para os dois Estados, RS e MT. O método Sikora e sua versão TSM reproduziram os valores de pH obtidos com o método SMP para os solos do MT e portanto podem ser usados para a recomendação de calcário. Para os solos do RS, o método TSM mostrou-se mais eficiente do que o método Sikora na reprodução dos valores de pH obtidos com o método SMP, sendo o mais indicado para substituí-lo nos laboratórios de análise de solos deste Estado e na recomendação de calcário.

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Orientador: Cecilia Amelia de Carvalho Zavaglia / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecânica / Made available in DSpace on 2018-08-24T20:34:28Z (GMT). No. of bitstreams: 1 Cardoso_HugoAnaniasInacio_D.pdf: 8008219 bytes, checksum: ac8d13454298a5718b0e0051a87eb944 (MD5) Previous issue date: 2014 / Resumo: O fosfato tricálcico (TCP) é um dos fosfatos de cálcio mais importantes dentre os utilizados como biomateriais devido à sua biocompatibilidade, bioatividade, biorreabsorbilidade e osteocondutividade. A fase ? (?-TCP) se destaca, principalmente, devido à sua conversão em hidroxiapatita deficiente em cálcio após implantação. Entretanto, é difícil obter ?-TCP de elevada pureza, o que prejudica sua reatividade e seu desempenho in vivo. O objetivo principal deste trabalho é sintetizar ?-TCP de elevada pureza. Para isso, o pó de ?-TCP foi obtido via reação de estado sólido. Os reagentes precursores foram sintetizados em laboratório a fim de se diminuir o nível de impurezas, principalmente o magnésio. Após analisados e validados, os reagentes foram misturados nas devidas proporções e o pó de ?-TCP calcinado sob diversos protocolos: diferentes temperaturas sob mesmo tempo de patamar; mesma temperatura sob diferentes tempos de patamar; mesmo tempo e temperatura de patamar com condições de resfriamento distintas. Analisou-se a influência de cada variável na cinética da reação: tempo, temperatura, resfriamento. Foi obtido pó de ?-TCP (2g) com 100% de pureza sob temperaturas (1265ºC) e tempos (2h) menores que os registrados em literatura, sem a necessidade de choque térmico. O protocolo foi validado também para grandes quantidades de material (50g), em que o nível de pureza também foi de 100% / Abstract: Tricalcium phosphate (TCP) is one of the most important calcium phosphates used as biomaterials due to their biocompatibility, bioactivity, osteoconductivity and bioresorbability. Among them, ?-TCP goes beyond due to its conversion into calcium deficient hydroxyapatite after implantation. However, it is difficult to obtain high purity ?-TCP, which prejudices its reactivity and its performance in vivo. The main purpose of this work is to synthesize high purity ?-TCP. For this, ?-TCP powder was obtained by solid state reaction. The precursor reagents were synthesized in the laboratory in order to reduce the level of impurities, particularly magnesium. After analyzed and validated, reagents were mixed in the proper proportions and ?-TCP powder calcined under various protocols: variable temperature and constant time; constant temperature and variable time; constant time and temperature with different cooling conditions. The influence of each variable on the reaction kinetics was evaluated: time, temperature and cooling. ?-TCP powder (2g) was obtained with 100 % purity at temperatures (1265 °C) and times (2h) lower than those mentioned in the literature without thermal shock. The protocol was also validated for more material mass (50g), wherein the purity level was also 100% / Doutorado / Materiais e Processos de Fabricação / Doutor em Engenharia Mecânica

Les sulfoximines sont une famille de composés dont les domaines d’applications sont très variés. Elles sont utilisées comme auxiliaires, ou ligands pour la synthèse asymétrique et répertoriées comme groupements à forts potentiels dans des composés biologiquement actifs. Les sulfoximines fluorées sont bien plus rares et difficiles d’accès, mais de par les propriétés spéciales induites par le fluor, ont récemment attirées l’attention. Elles ont notamment été utilisées avec succès en tant que réactifs de (per)-fluoroalkylation ou comme groupements super-électroattracteurs. Cependant, il n’y a que de rares exemples de sulfoximines fluorées dans des composés bioactifs. De plus, à notre connaissance, les S-perfluoroalkyl sulfoximines n’ont encore jamais été utilisées comme ligands de métaux ou organocatalyseurs.La thèse porte sur le développement de la synthèse et la fonctionnalisation des sulfoximines fluorées pour la préparation de ligands et d’organocatalyseurs, notamment en version énantiopures. Elle est divisée en 3 chapitres.Le premier chapitre porte sur la synthèse des sulfoximines et des sulfilimines fluorées énantiopures. Sur différentes étapes de la synthèse de ces composés, plusieurs méthodes ont été utilisées, par exemple, la séparation de diastéréoisomères par l’acide de camphorsulphonique, l’oxydation asymétrique de Kagan, Modena, Uemura et aussi l’imination oxydante asymétrique. La CFS (Chromatographie par Fluide Supercritique) semi-préparative a permis de séparer les différents énantiomères des sulfilimines fluorées. L’oxydation des sulfilimines a permis d’obtenir les sulfoximines énantiopures avec de bons rendements. Ces sulfilimines et sulfoximines ont des configurations absolues stables, leurs caractéristiques optiques ont été mesurées ainsi que leurs structures ont été déterminées par diffraction des rayons-X. Le deuxième chapitre est principalement axé sur la N-fonctionnalisation des sulfoximines et leurs développements comme ligands et organocatalyseurs pour la catalyse. Nous avons pu montrer que l’utilisation des micro-ondes pour activer le couplage entre les sulfoximines libres et les aromatiques halogénés permettait d’obtenir de bons résultats et même de diminuer le temps de réaction par rapport à la méthode de chauffage conventionnel. Ce développement a également été utilisé pour préparer des ligands/organocatalyseurs chiraux. Ces nouveaux ligands, sulfoximines fluorées chirales, ont été appliqués dans des procédés de catalyse pour la réaction de Friedel-Crafts, de Biginelli et même comme réactif de Shibata asymétrique pour la trifluoromethylation. Nous avons montré également que ces composés peuvent être utilisés comme ligands ou organocatalyseurs chiraux dans la réaction de Mukaiyama ou de cycloaddition de Diels-Alder conduisant aux produits avec de bons rendements.Le dernier chapitre est basé sur la fonctionnalisation des sulfoximines fluorées par une réaction inédite d’ortholithiation. Dans cette partie, nous démontrons que la fonction sulfoximine fluorée joue le rôle de groupe ortho-directeur. Cela nous a permis d’accéder à une grande variété de sulfoximines orthosubstituées aux structures totalement nouvelles. Les produits dérivés ortho ont été utilisés comme réactifs dans de nombreuses réactions: dans la réaction de Sonogashira, dans la préparation de nouveaux réactif de trifluorométhylation et dans la synthèse d’analogues de composés biologiquement actifs. / Sulfoximines belong to a family of compounds with various application areas. They are used as auxiliaries or ligands for asymmetric synthesis and classified as high potential groups in biologically active compounds. Fluorinated sulfoximines are even more scarce and difficult to access, but special properties induced by fluorine, have attracted particular attention. They have been successfully used as (per)-fluoroalkylating reagent or as super-electron-withdrawing groups. However, there are only a few examples of fluorinated sulfoximines in bioactive compounds. To our knowledge, S-perfluoroalkylated sulfoximines have never been used as ligands of metals or organocatalysts so far.The Thesis focuses on the synthesis and functionalization of fluorinated sulfoximines for the preparation of chiral ligands and/or organocatalysts. It is divided into three chapters.The first chapter deals with the synthesis of enantiopure fluorinated sulfoximines and sulfilimines. During our synthesis, several methods were used, for example, separation of diastereoisomers by using camphorsulphonic acid, and the asymmetric oxidation of Kagan, Modena, Uemura as well as the asymmetric oxidizing imination. The SFC (Supercritical Fluid Chromatography) semi-preparative permits to separate the different enantiomers of fluorinated sulfilimines. Oxidation of sulfilimines led to the formation of enantiopure sulfoximines in good yields. These sulfilimines and sulfoximines are stable retaining their absolute configuration. Optical characteristics were measured and their structures were determined by X-ray diffractions. The second chapter focuses mainly on the N-functionalization of sulfoximines and their developments as organocatalysts and/or ligands for catalysis. Coupling reaction of free sulfoximines with halogenated aromatic under microwave activation led to the formation of products in good yields within short reaction time. This development has also been used to prepare chiral ligands/ organocatalysts. These new chiral fluorinated sulfoximines have been applied in catalytic processes for Friedel-Crafts reaction, Biginelli transformation and as Shibata’s asymmetric trifluoromethylation reagent. We also showed that these compounds may be used as chiral ligands or organocatalysts in Mukaiyama reaction or in Diels-Alder cycloaddition affording products in good yields.The last chapter is based on the functionalization of fluorinated sulfoximines by an ortholithiation reaction. In this part, we have demonstrated that the fluorinated sulfoximine function acts as ortho-directing group. This allowed us to access a wide variety of new ortho-substituted sulfoximine structures. Ortho-derivatives were used as reagents in Sonogashira reaction, in the preparation of novel trifluoromethylation reagents and in the synthesis of some biologically active compound analogues.

Introduktion: Daratumumab är en monoklonal antikropp som används för att behandla patienter med multipelt myelom (MM), en typ av blodcancer som har sitt ursprung i B-lymfocyter. Daratumumab binder till CD38 som normalt uttrycks på erytrocyternas yta och ger upphov till panreaktivitet vid förenlighetsprövning, som kan maskera kliniskt signifikanta antikroppar. Ditiotreitol (DTT), ett reducerande lösningsmedel, denaturerar den extracellulära domänen av CD38 och därmed hämmar inbindning av daratumumab. DTT-behandling av testerytrocyter vid förenlighetsprövning möjliggör detektion av kliniskt relevanta alloantikroppar.  Syfte: Att verifiera en metod för DTT-behandling av erytrocyter vid förenlighetsprövning, för att detektera alloantikroppar av klinisk relevans och lättare få fram blod till patienter som medicineras med Darzalex.  Metod & materiel: I studien ingick två plasmaprover från patienter med daratumumab behandling. Testerytrocyterna behandlades med olika DTT mängd (80, 160 och 320 L). DTT-behandlade samt obehandlade testerytrocyter testades mot plasmaproverna, negativ kontroll (anti-K) och positiv kontroll (anti-C) vid olika dagar från tillredningsdatum.  Resultat: Daratumumab interferens mot obehandlade testerytrocyter observerades. Reaktionen för samtliga DTT-behandlade testceller vid varje analystillfälle blev negativt, oavsett DTT mängd. Resultaten för den negativa kontrollen visade att det slog positivt vid DTT mängden 80 samt 160 µL och negativ vid 320 µL. Alla reaktioner för den positiva kontrollen var 4+ vid samtliga DTT mängder oavsett analysdag.  Slutsats:  DTT-behandling av erytrocyter inaktiverar CD38 som motverkar panreaktivitet vid serologiska analyser, för att upptäcka eventuella kliniskt signifikanta antikroppar hos patienter som behandlas med daratumumab. Den optimala DTT mängden är 320 µL/1 ml 1% testerytrocyt med upp till 15 dagars hållbarhet vid kylförvaring. / Introduction: Daratumumab is a monoclonal antibody used to treat patients with multiple myeloma (MM), a type of blood cancer that originates in B lymphocytes. Daratumumab binds to CD38, which is expressed on the surface of erythrocytes. This leads to panagglutination in compatibility testing and can mask clinically significant antibodies. Dithiothreitol (DTT), a reductant, denatures the extracellular domain of CD38, thereby inhibiting daratumumab from binding. DTT treatment of RBC-reagents enables the detection of clinically relevant alloantibodies. Purpose: To verify a method for DTT treatment of erythrocytes in compatibility testing, in order to detect alloantibodies of clinical relevance and to ensure that transfusion recipient with Darzalex medication receive compatible blood transfusion. Method: Two plasma samples from daratumumab treated patients were included. RBC-regents were treated with different amounts of DTT (80, 160 and 320 μL). DTT-treated and untreated RBC-reagents were tested against plasma samples, negative control (anti-K) and positive control (anti-C) on different days.  Results: Daratumumab interference with untreated RBC-reagents were observed.  DTT treated RBC-reagents however, showed negative reaction regardless of the amount of DTT used. Results for the negative control showed positive reaction with 80 and 160 µL DTT and negative at 320 µL. Reactions for the positive control were all 4+ no matter the amount of DTT and day it was analyzed.   Conclusion: DTT treatment of erythrocytes inactivates CD38, which prevents panagglutination, to detect any clinically significant antibodies in patients with daratumumab treatment. The optimal DTT amount is 320 µL / 1 ml 1% RBC-reagents and a shelf life of up to 15 days when stored cold.

This study described an alternative approach for flotation circuit optimization using a mathematical programming technique. Mathematical formulation resulted in mixed integer nonlinear programming problem. Experimental method was used to determine operating conditions of flotation circuit such as flotation circuit stream grades. These conditions were used as the basis for solving optimization problem formulated. The results of the optimization problem were obtaining by setting up the problem in MATLAB optimization toolbox. Performance of flotation circuit in terms of recovery with respect to operating conditions such as residence, number of cells and rate constant has been presented. Stage recoveries were presented as well as overall recovery of the entire flotation circuit. Optimization strategy used superstructure to compare and analyse different alternatives flotation circuits configurations on the basis of stage recoveries. Five circuit alternatives were evaluated are best performing were identified. The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS) software for analysing data derived from mathematical formulation developed for three stages of flotation circuit. Statistically, alternatives A and B can be considered as the most efficient alternatives for the Rougher recovery since they have the same highest means relative to others. Alternative B has the highest mean of 0.995 followed by Alternative A with a mean of 0.991, the least being alternatives D, C and E, respectively. These results imply that Alternative B could be the most efficient alternatives for overall circuit recovery against all other alternatives. One of the key findings were that recovery rate at the rougher stage is higher than the one at the cleaner stage. This results also showed flotation circuits with recycle streams yield comparatively good performance in terms of recovery at rougher stage as compared to circuit without recycle stream. / Civil and Chemical Engineering / M. Tech. (Chemical Engineering)

Ce travail de thèse présente le développement de nouvelles réactions de formation de liaisons carbone-carbone. Le premier chapitre décrit la cyanation d’arylzinciques par catalyse au cobalt à partir d’une source non toxique et bénigne, le N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS), et conduit à de bons rendements en benzonitriles correspondants. Dans cette réaction, le cobalt sert de catalyseur non seulement pour la formation des arylzinciques mais aussi pour la formation de liaisons C-CN. Les groupements fonctionnels, cétone et nitrile, sont permis lorsque le complexe de cobalt associé au ligand bipyridine est utilisé. Le deuxième chapitre porte sur l’homocouplage Csp3-Csp3. Un simple halogénure de cobalt permet de catalyser la dimérisation des halogénures d’alkyles et des acétates d’allyles avec de bons à d’excellents rendements. L’ajout d’iodure de sodium permet d’étendre cette réaction aux chlorures et tosylates d’alkyles. Le couplage croisé entre 2 halogénures d’alkyle différents a également été testé mais les conditions doivent être optimisées. Dans le troisième chapitre, le couplage croisé catalysé au cobalt entre des bromures vinyliques et des chlorures benzyliques est présenté. Des halogénures de vinyles et de benzyles porteurs de groupements electrodonneurs ou electroattrateurs peuvent ainsi être couplés efficacement avec rétention de la configuration de la double liaison. Un mécanisme radicalaire semble être impliqué. Enfin, le dernier chapitre décrit l’arylation d’une 2-phenylpyridine avec un arylzincique par catalyse au cobalt par activation d’une liaison C-H et conduit à de premiers résultats encourageants. / This thesis presents the development of cobalt-catalyzed carbon-carbon bonds formation. The first chapter describes a novel cobalt-catalyzed electrophilic cyanation of arylzinc species, employing benign and non-toxic N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) as the cyano source. In this reaction, cobalt catalyzes both the formation of arylzinc species and the cyanation reaction. Various benzonitriles are synthesized affording good to excellent yields. Using cobalt-bipyridine complexes instead of CoBr2, ketone and nitrile groups can be tolerated. The second chapter reports cobalt-catalyzed Csp3-Csp3 homocoupling reaction. A simple catalytic system could deliver dimers of a number of alkyl halides/pseudohalides and allylic acetates. Sodium iodide is crucial for the homocoupling of unactivated alkyl chlorides and tosylates. This method is extended to alkyl-alkyl cross-coupling; however, the conditions still need to be optimized. The third chapter describes a cobalt-catalyzed vinyl-benzyl cross-coupling. A variety of functionalized vinyl bromides and benzyl chlorides are efficiently coupled under mild conditions in good to excellent yields, with retention of Z/E configuration. A few mechanistic experiments indicate a single electron transfer involved. The last chapter discusses the progress on the cobalt-catalyzed arylation of 2-phenylpyridine with an arylzinc species by C-H activation and promising results are obtained.

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18808号 / 理博第4066号 / 新制||理||1585(附属図書館) / 31759 / 京都大学大学院理学研究科化学専攻 / (主査)教授 丸岡 啓二, 教授 時任 宣博, 教授 大須賀 篤弘 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

This dissertation elucidates a greater understanding of protein folding and unfolding processes during the lifetimes of electrospray and nano-spray droplets in laser electrospray mass spectrometry (LEMS) and nano-laser electrospray mass spectrometry (nano-LEMS) measurements, respectively. The similarity in mass spectral features obtained from conventional electrospray measurements for supercharged proteins with those of LEMS measurements suggested that supercharging phenomena occurs in the electrospray droplets during the droplet desolvation process. It was observed that the laser vaporization of protein from condensed phase into the electrospray droplets containing denaturing electrospray solution and a supercharging reagent resulted in the increase in ion abundance of higher charge states in comparison with electrospray measurements. Conversely, the addition of solution additives with varying gas phase basicity in the electrospray solvent resulted in charge reduction for unfolded protein upon laser vaporization from condensed phase into the charged electrospray droplets. The extent of charge reduction and the fraction of folded protein within the electrospray droplets was found to be dependent upon both the extent of protein denaturation in the solution prior to laser vaporization and the gas phase basicity of solution additives. The ability of the LEMS technique to analyze molecules from solution with high matrix effects was established by the successful detection of protein molecules from solution with high salt concentration. Experiments with LEMS enabled the detection of a protonated protein feature as the dominating peak in the mass spectra for up to 250 mM sodium chloride while conventional electrospray resulted in predominantly salt-adducted features, with suppression of the protonated protein ions for the salt concentration of 5 mM. This dissertation also expanded upon the use of a reaction system to measure the lifetimes of laser vaporized liquid droplets coupled with electrospray and nano-spray postionization mass spectrometry. Electrospray and nanospray droplet lifetimes were measured to be 4.5±0.6 ms and 1.4±0.3 ms using LEMS and nano-LEMS measurements, respectively. Time dependent protein folding measurements using LEMS revealed intermediate states during protein folding processes which are often limited in conventional electrospray measurements where bulk solution in manipulated (change in pH) to achieve protein folding. / Chemistry

Stereochemistry is important aspect of chemistry that customarily includes the study of the relative spatial arrangement of atoms within molecules (static stereochemistry), and the study of the stereochemical requirements and outcomes of chemical reactions (dynamic stereochemistry). These two branches complement each other in modern stereochemistry. Chiral organometallics feature prominently in organic synthesis as reactive intermediates. The possibility of exploring their stereochemistry in synthesis is associated with the configurational stability of the metal-bearing stereogenic center. We were interested in the configurational stability of lithiated and magnesiated nitriles. We developed a new series of lithio-cyclopropylnitriles bearing chelating groups for intramolecular coordination, as a possible strategy to impart configurational stability. Although this strategy has not yet been successful, using density functional theory (DFT) method, we addressed the effect of chelating groups on racemization via the "conducted tour" mechanism. We then explored metal-bromine exchange on enantiopure bromonitrile as alternative route to metalated nitriles. In this way, we demonstrated that magnesiated 2,2-diphenyl cyclopropylnitrile is configurationally stable on the macroscopic timescale. No other metallated nitrile has ever demonstrated configurational stability on this timescale. In contrast, bromine-lithium exchange of 1-bromo-2,2-diphenyl-cyclopropylnitrile demonstrated fast racemization under the same conditions. Another major project focused on conformational control of acyclic molecules. Using X-ray crystallography and NMR spectroscopy, we found that the 2,6-disubstituted aryl group eclipses its geminal hydrogen, and induces an antiperiplanar relationship of the geminal and vicinal hydrogens. Interestingly, anti-nitrile aldols or syn-ketone aldols bearing 2,6-disubstituted aryl groups demonstrate unanticipated remote effects on acyclic conformation: the 2,6-disubstituted aryl group prefers to be in a gauche position to the largest vicinal group. The minimization of allylic 1,3-strain and syn-pentane-like interaction works together in establishing this conformational preference. / Ph. D.