Submitted by FELIPE MANFROI FORTUNATO null (felipe.manfroi@hotmail.com) on 2017-03-12T18:59:44Z No. of bitstreams: 1 Tese - Felipe M Fortunato.pdf: 6655475 bytes, checksum: 3c80582e1359616323d24334fc381808 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-03-17T14:14:13Z (GMT) No. of bitstreams: 1 fortunato_fm_dr_araiq.pdf: 6655475 bytes, checksum: 3c80582e1359616323d24334fc381808 (MD5) / Made available in DSpace on 2017-03-17T14:14:13Z (GMT). No. of bitstreams: 1 fortunato_fm_dr_araiq.pdf: 6655475 bytes, checksum: 3c80582e1359616323d24334fc381808 (MD5) Previous issue date: 2017-02-22 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo desta Tese de Doutorado foi avaliar o método de adição de padrão interno empregando técnicas espectroscópicas. Inicialmente o método de adição de padrão interno foi aplicado no modo convencional na determinação de Ca e Mg em amostras biodiesel e urina por espectrometria de absorção atômica em chama de alta resolução e fonte contínua e na determinação de ureia em urina por espectroscopia Raman. Para fins comparativos, todas as amostras e materiais certificados foram também analisados pelos métodos de calibração externa, adição de padrão e padronização interna. Nitrato, Sr e Mn foram selecionados como padrões internos para ureia, Ca e Mg, respectivamente. Para avaliar a exatidão do método na determinação de Ca e Mg foram analisados nove materiais de referência certificados (CRM) e os resultados obtidos foram concordantes a 95% de confiança com os valores certificados (teste t). Para ureia a exatidão foi avaliada por meio de comparação dos resultados obtidos pelo método de adição de padrão interno e por um método de referência. Todos os resultados obtidos foram concordantes entre si (teste t pareado) ao nível de 95% de confiança. A exatidão do método também foi checada por meio de testes de adição e recuperação: Ca (93 – 119%), Mg (100 – 116%) e ureia (99 – 105%). A desvantagem do método de adição de padrão interno convencional foi o volume total de amostra utilizado, a quantidade de soluções analíticas empregadas e a baixa frequência analítica. No entanto, este problemas foram solucionados com o desenvolvimento de sistemas em fluxo e pelo uso de um gradiente de concentração. O método de adição de padrão interno por gradiente de concentração em fluxo foi avaliado na determinação de Na e K em amostras de biodiesel e urina por espectrometria de emissão atômica em chama e na determinação de etanol em gasolina por espectroscopia Raman. Lítio foi empregado como padrão interno para Na e K, e acetona foi utilizada como padrão interno para etanol. A exatidão do método na determinação de Na e K foi avaliada por meio da análise de cinco CRMs, e os resultados obtidos para Na foram concordantes a 95% de confiança com os valores certificados (teste t), para K os resultados apresentaram valores subestimados ao longo do trabalho (em torno de 80% de recuperação). Para determinação de etanol em gasolina a exatidão foi avaliada por meio da comparação dos resultados obtidos pelo método proposto e pelo método de referência, e todos os resultados obtidos foram concordantes entre si (teste t pareado) ao nível de 95% de confiança. A exatidão do método de adição de padrão interno por gradiente de concentração em fluxo também foi avaliada por meio de testes de adição e recuperação: Na (94 – 110%), K (73 – 86%) e etanol (99 – 104%). Os resultados obtidos utilizando o método de adição de padrão interno (convencional e em fluxo) em todas as aplicações apresentaram precisão e exatidão melhores ou comparáveis aos métodos de adição de padrão, padronização interna e calibração externa, mostrando ser uma estratégia de calibração eficiente para técnicas espectroscópicas. / The aim of this Doctoral Thesis was to evaluation of the internal standard addition method employing spectroscopic techniques. Initially, traditional standard addition method was applied for Ca and Mg determination in biodiesel and urine samples by high-resolution continuum source flame atomic absorption spectrometry and for urea determination in urine samples by Raman spectroscopy. For comparison purposes, all samples and certified materials were also analyzed by external calibration, standard addition and internal standardization methods. Nitrate, Sr and Mn were selected as internal standards for urea, Ca and Mg, respectively. In order to verify the accuracy for Ca and Mg determination were analyzed nine certified reference materials (CRM), the results were in agreement with certified values at the 95% confidence level (t-test). For urea, the accuracy was evaluated by comparison of the results obtained by internal standard addition and a reference method. All results were in agreement at 95% confidence level (paired t-test) with each other. The accuracy was also checked by addition and recovery tests: Ca (93 - 119%), Mg (100 - 116%) and urea (99 - 105%). The drawbacks of traditional internal standard addition were the total volume of sample used, the amount of analytical solutions employed and the lower sample throughput. However, these problems were solved with the development of flow systems and the use of a concentration gradient. The internal standard addition by flow gradient concentration was evaluated for Na and K determination in biodiesel and urine samples by flame emission atomic spectrometry and for ethanol determination in gasoline by Raman spectroscopy. Lithium was selected as internal standard for Na and K, and acetone was selected as internal standard for ethanol. The accuracy of the method for Na and K determination was evaluated by five CRMs analysis, and the results obtained for Na were in agreement with certified values at the 95% confidence level (t-test), for K the results presented underestimated values throughout the study (around 80% recovery). The accuracy for ethanol determination in gasoline was evaluated comparing the results obtained by the proposed method with the reference method. All results were in agreement at 95% confidence level (paired t-test) with each other. The accuracy of internal standard addition by flow gradient concertation method was also evaluated by addition and recovery tests: Na (94 - 110%), K (73 - 86%) e ethanol (99 - 104%). The results obtained by internal standard addition (traditional and flow modes) for all applications showed accuracy and precision better or comparable with traditional calibration methods (standard addition, internal standardization and external calibration), revealing to be an efficient calibration strategy for spectroscopic techniques. / FAPESP: 2012/23323-7

Ce mémoire de thèse se concentre sur le développement de réactions multicomposants énantiosélectives de dérivés 1,3-Dicarbonylés en présence d'un organocatalyseur, en vue de préparer des motifs polyhétérocycliques fusionnés.Dans un premier temps, nous décrivons nos résultats initiaux sur une réaction multicomposants énantiosélective avec des énals et des amines primaires simples. Au vu des faibles énantiosélectivités obtenues, des amines fonctionnalisées ont ensuite été introduites dans ces réactions, permettant ainsi de synthétiser des pyrrolopiperazines et d'autres molécules hétérocycliques polyfonctionnalisées énantioenrichies, toutes obtenues avec des rendements intéressants et des énantiosélectivités élevées.Ayant utilisé avec succès des β-Cétoamides α-Méthyléniques dans ces réactions multicomposantes, nous avons réalisé par ailleurs que leur simple addition de Michael sur des oléfines pauvres en électrons n'avait jamais été décrite en version organocatalysée. Nous avons donc étudié leur réaction avec des nitrooléfines en présence d’organocatalyseurs chiraux, et les produits attendus ont alors été obtenus avec de bons rendements et d'excellentes diastéréo- et énantiosélectivités. / This thesis focuses on the development of enantioselective multicomponent reactions with 1,3-Dicarbonyls in the presence of an organocatalyst, to synthesize fused polyheterocyclic motives.At first, we describe our initial results on an enantioselective multicomponent reaction with enals and simple primary amines. In view of the low enantioselectivities achieved, functionalized amines were then introduced in these reactions, thereby synthesizing enantioenriched pyrrolopiperazines and other polyfunctionalized heterocyclic molecules, all obtained with attractive yields and high enantioselectivities.Having successfully used methylene β-Ketoamides in these enantioselective MCRs, we realized also that their simple Michael addition to electron-Poor olefins had never been described in organocatalytic conditions. We therefore studied their reaction with nitroolefins in the presence of various chiral organocatalysts, and the expected products were pleasingly obtained with high yields, excellent diastereo- and enantioselectivities.

This paper combines data from two different international research studies that used problem posing in analyzing elementary teacher candidates’ understanding of rational numbers. In 2007, a mathematics educator from the United States and a mathematician from Northern Ireland collaborated to investigate their respective elementary teacher candidates’ understanding of addition and division of fractions. A year later, the same US mathematics educator collaborated with a mathematics educator from South Africa on a similar research project that focused solely on the addition of fractions. The results of both studies show that elementary teacher candidates from the three different continents share similar misconceptions regarding the addition of fractions. The misconceptions that emerged were analyzed and used in designing teaching strategies intended to improve elementary teacher candidates’ understanding of rational numbers. The research also suggests that problem posing may improve their understanding of addition of fractions.

La réactivité de l’α-bromoacrylate d’éthyle et du benzylidène malonate d’éthyle vis à vis des dialkylzincs en milieu aérobie a été étudiée afin d’évaluer la capacité des radicaux α-alcoxycarbonyle tertiaires à évoluer par SH2 sur le métal pour conduire à un énolate de zinc. Le travail expérimental réalisé à partir de l’α-bromoacrylate d’éthyle a permis la synthèse de cyclopropanes et de céto-esters. Dans le cas des benzylidène malonates la réversibilité de l’addition du diéthylzinc sur le substrat, a été mise en évidence. L’effet inhibiteur d’additifs tels que TMSCl ou CuCl concourt à indiquer que les peroxydes de zinc formés dans le milieu pourraient y tenir un rôle clé. L’étude théorique a mis en évidence pour les 2 substrats étudiés, le rôle crucial de la stabilisation de l’énolate formé sous la forme d’un chélate à 5 ou 6 chaînons. Les carbozincations d’ynamides via le CuI ou le FeCl2 en présence de dialkylzincs ont été étudiées pour la synthèse régio-et stéréosélective d'énamides tri- ou tétrasubstitués. Le CuI s’est montré plus performant et moins substrat-dépendant que FeCl2. Une étude théorique a été réalisée afin de mieux comprendre ce phénomène. Enfin, l'addition intermoléculaire des radicaux sulfanyle sur les ynamides a été revisitée. Les calculs théoriques et les résultats expérimentaux montrent que la régio- et stéréosélectivité de la réaction dépendent de la nature du substituant porté par le carbone en β de l’atome d’azote et des conditions expérimentales. L’addition intermoléculaire inédite d’un radical carboné électrophile sur ces substrats a pu être décrite et ouvre de nouvelles perspectives quant à la synthèse d’énamides tétrasubstitués originaux. / The reactivity of ethyl α-bromoacrylate and ethyl benzylidene malonate towards dialkylzincs in aerobic medium was studied in order to evaluate the capacity of tertiary α-alcoxycarbonyl radicals to undergo SH2 at zinc leading to a zinc enolate. The use of ethyl α-bromoacrylate allowed the synthesis of cyclopropanes and keto-esters. With the second substrate, the addition of the alkyl group was shown to be reversible. The inhibitor effect of additives like TMSCl or CuCl suggested that zinc peroxydes formed in situ could play a key role in the process. Theoretical studies highlighted the crucial role of the stabilization of the zinc enolate through the formation of a 5 or 6-membered chelate. Regio- and stereoselective synthesis of tri- and tetra-substituted enamides was achieved through the carbozincation of ynamides in the presence of dialkylzincs and CuI or FeCl2 as catalyst. CuI was shown to be more efficient and less substrate-dependent than FeCl2. Molecular modelings were performed to better understand this phenomen. Finally, intermolecular addition of sulfanyl radicals onto ynamides was revisited. Theoretical calculations and experimental results showed that the regio- and stereo-selectivity of the process depended on the nature of the substituent on the carbon in β position of the nitrogen atom and on experimental conditions. Unprecedented intermolecular addition of a carbon-centered radical has been described and opened new perspectives for the synthesis of original tetrasubstituted enamides.

Ces travaux s’articulent autour de dérivés saccharidiques de type exo-glycals ou C-glycosides pour lesquels de nouvelles méthodologies synthétiques ainsi que des applications dans le domaine de la biologie ont été développées. Dans un premier temps, l’addition de nucléophiles soufrés et carbonés sur le carbone anomérique de différents exo-glycals activés a été réalisée, permettant un accès efficace à de nouveaux S-glycosides tertiaires ainsi qu’à des γ-glycoamino acides anomériques. Ces derniers ont été utilisés pour l’élaboration de peptides linéaires mixtes α/γ dont les propriétés de structuration ont ensuite été étudiées par RMN, IR, CD et modélisation moléculaire. De nouvelles plates-formes glycopeptidiques multifonctionnelles ont été préparées par cyclisation de ces peptides. Dans un second temps, le développement de peptidomimétiques ciblant le récepteur neuropiline-1, impliqué dans l’angiogenèse tumorale, a été entrepris. En s’appuyant sur des études de modélisation moléculaire, certains composés ont montré une bonne affinité pour le récepteur NRP-1 et l’un des composés a montré des propriétés prometteuses pour l’inhibition de la formation de tubules / This work is focused on the development of new synthetic pathways for exo-glycals functionalization and synthesis of bioactive compounds. The first part of this manuscript describes the efficient preparation of new tertiary S-glycosides and γ-glycoamino acids via Michael addition of thiols derivatives and carbanions on anomeric carbon of exo-glycals. The obtained γ-glycoamino acids were then incorporated in α/γ mixed peptides and their structural properties were studied by NMR, IR, CD and molecular modelling studies. Furthermore, cyclic multivalent platforms were built by intramolecular cyclization of these entities. The second part of the manuscript concerns the elaboration of peptidomimetics targeting neuropilin-1 receptor, implicated in tumor angiogenesis. Based on molecular modeling studies, some compounds showed interesting binding affinity for NRP-1 receptor and one of them displayed promising properties toward inhibition of tubule formation

La trypanosomiase humaine africaine, la maladie de Chagas et les leishmanioses sont des maladies parasitaires qui représentent un problème majeur de santé publique dans de nombreux pays et notamment ceux en voie de développement. Afin de trouver de nouveaux candidat-médicaments contre ces parasites, deux séries chimiques ont été étudiées : les diarylidèneacétones et les 2,6-diaryl-4H-tetrahydrothiopyranones.Précédemment initiée au laboratoire, l'étude approfondie de la série diarylidèneacétone a nécessité la mise au point et l'optimisation de protocoles. Une nouvelle méthodologie de synthèse des (hétéro)diarylidèneacétones dissymétriques par palladocatalyse a ainsi été développée en collaboration avec le Pr. T. J. Müller (Université de Düsseldorf). En dépit d'excellentes activités antiparasitaires, la plupart des diarylidèneacétones synthétisées se sont révélées trop toxiques sur les cellules humaines.Les 2,6-diaryl-4H-tétrahydrothiopyranones et leurs S-oxydes ont été conçues pour résoudre ce problème de toxicité. Agissant comme prodrogues, ces molécules sont susceptibles de régénérer les diarylidèneacétones parentes par β-élimination du groupement soufré intracyclique. Peu décrite dans la littérature, la synthèse diastéréosélective de ces structures a été intégralement mise au point et généralisée à de nombreuses substitutions. Les résultats obtenus prouvent que la toxicité des produits a été grandement diminuée tout en maintenant une activité antiparasitaire importante, ce qui valide l'approche de la stratégie prodrogue. / Human African trypanosomiasis, Chagas disease and leishmaniasis are parasitic diseases that significantly affect the populations and thus the economy of many developing countries. With the aim of developing new therapeutic agents to cure these diseases, we focused our research on two series: the diarylideneacetone and the 2,6-diaryl-4H-tetrahydrothiopyranone series.To complete and expend preliminary results that had been previously obtained in our laboratory, a generalization and an optimization of the protocols was intended. Thus, a novel Palladium-catalyzed synthesis of (hetero)dissymmetric diarylideneacetones was developed and optimized in collaboration with Prof. T. J. Müller (University of Düsseldorf). In spite of excellent antiparasitic activities, most of the diarylideneacetones were toxic toward human cells.2,6-Diaryl 4H-tetrahydrothiopyranones and their related S-oxides were designed to cope with major toxicity issues. Acting as prodrugs, these molecules are prone to undergo β-elimination of the sulfurated intracyclic group, regenerating the parent diarylideneacetone. The diastereoselective synthesis of this scaffold is not extensively described in the literature. Consequently, novel diastereoselective methodologies have been developed and generalized to a wide panel of substitution patterns. Results of the biological assays demonstrated that sulfide and S-oxide prodrugs displayed a lowered toxicity while the potency was maintained, thus confirming the validity of the prodrug strategy.

Os Ferros Fundidos de Alto Cromo (FFAC), por apresentarem excelentes propriedades tribológicas, têm sido amplamente utilizados em aplicações específicas envolvendo elevadas perdas de material por abrasão, especialmente no setor da mineração. Entretanto, a demanda por materiais com maior resistência ao desgaste aumenta continuamente, sendo necessárias novas pesquisas nesta área. Portanto, o presente trabalho objetiva avaliar a utilização do nióbio para aumentar, ainda mais, a resistência à abrasão dos FFAC\'s. Por outro lado, quando o FFAC é utilizado na fabricação de peças com geometrias irregulares (por exemplo, rotores de bombas), o componente pode apresentar diferentes níveis de refinamento da microestrutura, entre as regiões finas e espessas, devido às variações na taxa de resfriamento. No presente trabalho foi avaliado, o efeito do grau de refinamento da microestrutura, e a interação do refinamento com a adição de nióbio, na resistência ao desgaste abrasivo dos FFAC\'s. Para tanto, foram desenvolvidos quatro estudos principais: no primeiro estudo foram fabricados blocos de FFAC variando o grau de refinamento da microestrutura e foi mostrado que: grandes incrementos no grau de refinamento resultam em maiores perdas de massa por abrasão. Nas microestruturas menos refinadas, os carbonetos de cromo M7C3, de maior tamanho, são menos susceptíveis ao micro trincamento e podem, ocasionalmente, atuar como barreiras ante os eventos abrasivos. Em uma segunda série de experimentos, foi avaliada a interação do efeito do grau de refinamento da microestrutura com a adição de nióbio em teores baixos (1 %); mostrando que, para microestruturas com alto grau de refinamento, adições de nióbio reduzem as perdas de massa por abrasão em até 50 %. Em uma terceira série de experimentos foi avaliada a interação dos efeitos da adição de nióbio e de molibdênio. Quando comparado com a liga isenta de molibdênio, adições simultâneas de nióbio e molibdênio resultaram em microestruturas mais refinadas, com maior microdureza da matriz, e com carbonetos de nióbio (NbC) de maior dureza. Para condições de desgaste abrasivo por baixos esforços, onde o desgaste foi mais acentuado na matriz, adições simultâneas de nióbio e molibdênio resultaram em aumentos da resistência á abrasão dos FFAC estudados. Na última etapa do trabalho foi adicionado 3 % de nióbio em um liga de FFAC com composição química inicial hipereutética (25%Cr/3%C), a qual apresentaria carbonetos primários de cromo M7C3 de grande tamanho que induziriam comportamento frágil do material quando exposto ao desgaste. Porém, a adição de nióbio resultou em um FFAC com microestrutura mais refinada (eutética), contendo NbC\'s compactos e por conseguinte, mais resistente ao desgaste abrasivo. / High Chromium Cast Irons (HCCI\'s), because of their excellent tribological properties, have been widely used for specific applications involving high wear rates by abrasion, especially in the mining sector. However, the demand for materials with higher wear resistance is continuously growing and thus further research is needed in this area. For that reason, the current work purposes to assess the use of niobium to further increase the wear resistance of HCCI\'s. On the other hand, when HCCI is used for manufacturing components with irregular geometries (e.g. pump impellers), the components thin and thick regions can contain different levels of structure refinement due to variation in their cooling rates. In this work, the effect of structure refinement and the interaction between structure refinement and niobium addition on the abrasion resistance of HCCI\'s were evaluated. For that purpose, four systematic main studies were developed: in the first study, blocks of HCCI were manufactured varying the structure refinement and it was shown that large increases in the degree of structure refinement result in higher wear mass losses by abrasion. In less refined microstructures, the larger M7C3 chromium carbides are less susceptible to microcracking and can occasionally act as a barrier to abrasive particles. In the second series of experiments, the interaction between structure refinement and niobium addition in low concentrations (1 %) was evaluated; showing that for more refined microstructures, niobium additions reduce the mass losses by abrasion up to 50 %. In the third series of experiments, the interaction between niobium and molybdenum additions was evaluated. Compared to molybdenum-free alloy, simultaneous additions of niobium and molybdenum resulted in a more refined microstructure, higher hardness of the matrix and harder niobium carbides (NbC). For Low Stress Sliding Abrasion (LSSA) wear configuration, where wear was more pronounced in the matrix, simultaneous addition of niobium and molybdenum resulted in increase of abrasion resistance in the studied HCCI. In the last stage of this work, 3 % of niobium were added in an HCCI alloy with hypereutectic initial chemical composition (25%Cr/3%C), which presents primary large sized chromium carbides that induce a brittle behavior of the HCCI when subjected to wear. However, the niobium addition resulted in a more refined microstructure (eutectic) HCCI containing compact-shaped NbC carbides, and consequently in more resistance to abrasive wear.

De nombreuses études ont montré qu’une activation d'indices moteurs (mouvement d’approche ou de retrait ; Cretenet et Dru 2004) ou spatiaux (verticale ou horizontale ; Casasanto, 2009) était de nature à influencer un jugement ou des réponses finales. Dans le cadre des théories de la cognition incarnée, ce travail examine l’effet de l’activation synchrone ou asynchrone de ces indices comme étant révélatrice de processus cognitifs. Dans cette perspective, nos travaux, présentés sous la forme de deux articles, ont pour objectif d’analyser l’effet de ces activations, impliquant la théorie de la correspondance de polarité (Proctor et Cho, 2006), sur la résolution d’opérations arithmétiques, comme l’expression d’une combinatoire cognitive particulière. De plus, cette thèse supporte l’idée qu’une analogie entre la PCE et ces résultats peut être faite. En effet, le cœur de notre travail consiste défendre l’idée que quelque soit les indices conceptuels (motivationnel ou émotionnel) activés, de mêmes effets sont observés, traduisant la mise en jeu d’un même système de codage de polarités. Lors de l’activation d’indices de polarité (motivationnelle ou émotionnelle), un phénomène de compatibilité s’opère influençant le raisonnement mathématique.Nous proposons d'étudier l'effet d’un mouvement moteur (effectué) ou spatial (perçu) combinant deux dimensions spatiales (latérale et verticale) simultanément ou non sur la performance numérique. L’objectif est d’analyser l’influence de conditions de congruence ou de non congruence sur la résolution d’opérations arithmétiques. L’idée est de montrer qu’une activation synchrone d’indices moteurs ou spatiaux influencerait une combinatoire cognitive telle que la multiplication (Article 1) ; tandis qu’une activation asynchrone d’indices spatiaux influencerait une combinatoire cognitive telle que l’addition (Article 2).Ces travaux démontrent pour la première fois comment des combinatoires perceptives ou motrices déterminent des combinatoires cognitives. / Several studies have shown that an activation of motors (approach-avoidance behaviors, Cretenet & Dru 2004) or spatial cues (vertical or horizontal, Casasanto, 2009) is likely to influence the affective judgment or the final responses. In regards of the theories of embodiment, this studies examine the effect of combined (synchronous or asynchronous) motor and spatial cues on mathematical reasoning as revealing cognitive processes. In this perspective, our work, presented in two articles, with the aim to analyze the effect of these activations, involving the theory of polarity correspondence (Proctor & Cho, 2006), on the resolution of arithmetic operations, as the expression of a particular cognitive functioning. Furthermore, this thesis supports the idea that this operation has some analogy with the polarity correspondence effect (PCE). Indeed, our work supports the idea that whatever the activated conceptual cues are (motivational or emotional), the same effects are observed - a similar system is activated, coded as polarities which might be indicative of the PCE. When the activation of polarity indices (motivational or emotional), a phenomenon of compatibility occurs that also influences mathematical reasoning.We investigate the effect of a motor (performed) or spatial (perceived) movement combining two spatial dimensions (laterality and verticality) simultaneously or not on numerical performance. The objective is to investigate the influence of congruence or noncongruence conditions on the resolution of arithmetic operations. When a synchronous activation of peripheral cues (motor or spatial) is activated, we would observed an effect on mathematical reasoning, such as multiplication (Article 1); while when an asynchronous activation, deferred in time and space, of spatial cues would influence a mathematical reasonning, such as addition (Article 2). For the first time, studies demonstrate how a particular combination of perceptual or motor activations reveals some correspondent cognitive mechanism.

Au cours de cette thèse, nous avons rapporté que la combinaison unique de l'hexafluoroisopropanol (HFIP), utilisé comme solvant, et des conditions hyperbares (10-15 kbar) permet une addition sans précédent de nucléophiles-1,4 pauvres, comme les amines aromatiques, sur des récepteurs Michael encombrés, sans promoteur externe. De plus, l'addition d'hétéro-Michael d'anilines fonctionnellement substituées sur des esters insaturés-α,β est définie par la différence d'acidité entre le solvant et l'amine. La réaction avec des anilines plus basiques se déroule facilement dans le méthanol. En revanche, les solvants protiques très polaires comme les alcools fluorés (HFIP et TFE) favorisent l'addition d'aza-Michael de nucléophiles plus faibles. Enfin, une méthode verte et sans catalyseur de construction de nouveaux dérivés d'acides aminés contenant des fragments d'adamantane et d'aziridine a été développée. Et il est prouvé que la réaction d'aza-Michael initie la formation de l’hétérocycle. / Along this PhD work, we have reported that the unique combination of hexafluoroisopropanol (HFIP), employed as solvent, and hyperbaric conditions (10-15 kbar) allows unprecedented 1,4-addition of poor nucleophiles such as aromatic amines onto sluggish (cumbersome) Michael acceptors without any promoter nor work-up. Moreover, The hetero-Michael addition of functionally substituted anilines to α,β-unsaturated esters is significantly defined by the difference of acidity between the solvent and the amine. Reaction with more basic anilines proceeds smoothly in methanol. In contrast, very polar protic solvent such as fluorinated alcohols (HFIP and TFE) favor the aza-Michael addition of more weak nucleophiles. Finally, green and catalyst-free method of new amino acid derivatives construction containing adamantane and aziridine fragments was developed. And it is proved that aza-Michael reaction initiates the formation of heterocycle.

Läromedel har en styrande roll i många matematikklassrum vilket innebär att läromedel påverkar vilka uppgifter som elever erbjuds i undervisningen. Men vad är det som erbjuds i läromedel? Syftet med studien var att undersöka hur uppgifter i svenska läromedel för årskurs 1 behandlar tals additiva del-helhetsrelationer. Teorin om handlingserbjudanden och begrepp från variationsteorin har använts i syfte att utifrån ett funktionellt perspektiv undersöka vad som erbjuds i läromedel. Studien genomfördes genom en kvantitativ innehållsanalys och en kvalitativ dataanalys av fem läromedelsserier. Den kvantitativa analysen visar förekomsten av uppgifter som behandlar tals additiva del-helhetsrelationer. Den visar också att elever erbjuds olika representationsformer samt att växla mellan dessa. Språk, symbol och bild är de som erbjuds i störst utsträckning medan konkret modell endast erbjuds i ett fåtal uppgifter. Vidare visar den kvalitativa analysen skillnader i hur uppgifter är utformade för att synliggöra tals additiva del-helhetsrelationer. Uppgifternas form erbjuder elever skillnader i struktur, systematik samt i vilket utsträckning de olika sätt på vilket ett tal kan delas upp synliggörs. För att undervisningen ska främja elevers förståelse för tal och relationen mellan tal behöver läraren vara medveten om de möjligheter som läromedel erbjuder samt eventuella begränsningar. Detta för att kunna rikta elevers uppmärksamhet mot det som avses att läras. / Mathematics textbooks have a governing role in many mathematics classrooms which means that textbooks affect the tasks that learners are afforded in teaching. But what is afforded in these textbooks? The aim of the study was to investigate how Swedish textbooks for first grade treats additive part-whole relations of numbers. The theory of affordances and concepts from the variation theory has been used for the purpose, that based on a functional perspective to investigate what is afforded in textbooks. The study was conducted through a quantitative content analysis and a qualitative data analysis of five series of textbooks. The quantitative analysis shows the existence of tasks that treat additive part-whole relations of numbers. It also shows that learners are afforded different forms of representations and to switch between them. Language, symbol and image are afforded to the greatest extent while concrete model is only afforded in a few tasks. Furthermore, the qualitative analysis shows differences in how tasks are designed to make the additive part-whole relations of numbers visible. In the design of tasks, learners are afforded differences in structure, systematics and the extent to which the different ways in which a number can be divided are made visible. To promote learners´ understanding of additive part-whole relations of numbers, the teacher needs to be aware of the opportunities that textbooks can afford, as well as limitations. This is to be able to draw the learners´ attention to what is intended to be learned.