Notre étude a pour objet la conception, la synthèse ainsi que l’étude structurale d’architectures supramoléculaires obtenues par auto-assemblage, en se basant sur les concepts de la tectonique moléculaire. Cette branche de la chimie supramoléculaire s’occupe de la conception et la synthèse de molécules organiques appelées tectons, du grec tectos qui signifie constructeur. Le tecton est souvent constitué de sites de reconnaissance branchés sur un squelette bien choisi. Les sites de reconnaissance orientés par la géométrie du squelette peuvent participer dans des interactions intermoléculaires qui sont suffisamment fortes et directionnelles pour guider la topologie du cristal résultant. La stratégie envisagée utilise des processus d'auto-assemblage engageant des interactions réversibles entre les tectons. L’auto-assemblage dirigé par de fortes interactions intermoléculaires directionnelles est largement utilisé pour fabriquer des matériaux dont les composants doivent être positionnés en trois dimensions (3D) d'une manière prévisible. Cette stratégie peut également être utilisée pour contrôler l’association moléculaire en deux dimensions (2D), ce qui permet la construction de monocouches organisées et prédéterminées sur différents types des surfaces, tels que le graphite.Notre travail a mis l’accent sur le comportement de la fonction amide comme fonction de reconnaissance qui est un analogue du groupement carboxyle déjà utilisé dans plusieurs études précédentes. Nous avons étudié le comportement d’une série de composés contenant un noyau plat conçu pour faciliter l'adsorption sur le graphite et modifiés par l'ajout de groupes amide pour favoriser la formation de liaisons hydrogène entre les molécules ainsi adsorbées. La capacité de ces composés à former de monocouches organisées à l’échelle moléculaire en 2D a été examinée par microscopie à effet tunnel, etleur organisation en 3D a également été étudiée par cristallographie aux rayons X. Dans notre étude, nous avons systématiquement modifié la géométrie moléculaire et d'autres paramètres afin d'examiner leurs effets sur l'organisation moléculaire. Nos résultats suggèrent que les analyses structurales combinées en 2D et 3D constituent un important atout dans l'effort pour comprendre les interactions entre les molécules adsorbées et l’effet de l’interaction avec la surface du substrat. / Our study involves the design, synthesis and structural analysis of supramolecular architectures obtained by self-assembly, based on the concepts of molecular tectonics. This branch of supramolecular chemistry explores the properties of molecules called tectons,from the Greek word tectos, meaning builder. Tectons typically incorporate sites of recognition connected to well-chosen skeletons with defined geometries. The sites of recognition, oriented by the geometry of the skeleton, can participate in intermolecular interactions that are sufficiently strong and directional to control the topology of the resulting assembly. This strategy is thereby based on self-assembly processes involving reversible interactions between tectons. Self-assembly directed by strong directional intermolecular interactions is widely used to produce materials whose components must be positioned in three dimensions (3D) in a predictable way. This strategy can also be used to control molecular association in two dimensions (2D), thereby allowing the construction of predictably organized and predetermined nanopatterns on various surfaces, such as graphite.Our work has focused on the behavior of the amide groups as primary sites of intermolecular interaction. These groups are analogues of carboxyl groups, which have been widely used in previous studies of directed molecular assembly. We have studied the 3D and 2D association of compounds with flat cores designed to favor the formation of sheets and to facilitate adsorption on graphite, modified by the addition of amide groups to promote the formation of intermolecular hydrogen bonds. The ability of these compounds to form predictably ordered 2D nanopatterns has been examined by scanning tunneling microscopy, and their organization in 3D has also been investigated by X-ray crystallography. In our study, we have systematically altered molecular geometry and other parameters to examine their effect on molecular organization. Our results suggest that combined structural analyses in 2D and 3D are an important asset in the effort to understand why molecules aggregate in particular ways and how these preferences can be altered by underlying surfaces.

Neste trabalho, enzimas álcool-desidrogenases provenientes de fungos marinhos e a lipase imobilizada de Candida antarctica foram utilizadas para produção de compostos de interesse sintético e biológico. No capítulo 1, enzimas álcool-desidrogenases de fungos isolados da alga marinha Bostrychia radicans foram empregadas em reações de redução de cetonas fluoradas 1-5. Os fungos identificados como Botryosphaeria sp. CBMAI 1197, Eutypella sp. CBMAI 1196, Hidropisphaera sp. CBMAI 1194 e Xylaria sp. CBMAI 119 atuaram como biocatalisadores nestas reações levando à produção de álcoois com elevada pureza enantiomérica. O fungo Botryosphaeria sp. CBMAI 1197 destacou-se frente aos demais microrganismos, produzindo os álcoois (S)-2,2,2-trifluoro-1-feniletanol (1a) e (R)-1-(2,4,5-trifluorofenil)etanol (3a) com excelentes conversões (100% e 97%) e excessos enantioméricos (ee >99%). Este fungo também apresentou enzimas álcool-desidrogenases ativas frente a cetonas dicarboniladas 4-5, produzindo os álcoois 4,4,4-trifluoro-1-fenil-1,3-butanodiol (4a) e 4,4,4-trifluoro-1-(2-naftalenil)-1,3-butanodiol (5a) com 100% de conversão em ambos os casos e com purezas enantioméricas respectivas a 99% e 97%. Este foi o primeiro estudo realizado no Brasil com fluorocetonas dicarboniladas e com os fungos isolados da alga marinha Bostrychia radicans. No capítulo 2, a lipase comercial de Candida antarctica foi o biocatalisador empregado em reações de aminólise entre os ésteres linoleato de etila (1) e salicilato de etila (3), a amina graxa N-dodecilamina (2) e os aminoálcoois (4-9). A amina graxa N-dodecilamina (2) também foi utilizada em reações com o linoleato de etila (1), onde a lipase de Candida antarctica produziu a respectiva amida graxa 10 com rendimentos superiores a 95%. Os aminoálcoois foram selecionados para reações com o salicilato de etila (3), onde a lipase exibiu quimiosseletividade pelo grupo amino, produzindo predominantemente amidas fenólicas (12-19) com rendimentos entre 23-68%. A enzima CALB apresentou quimiosseletividade reduzida na reação com o 5-aminopentanol (6) onde os produtos amida 14 e éster 15 foram obtidos com rendimentos de 44 e 33%, respectivamente. O produto 2-hidroxi-N-(2-hidroxipropil)benzamida (19) foi obtido com rendimento superior a 90% a partir da reação catalisada pela lipase de Candida antarctica. Este produto foi selecionado como intermediário para a síntese de uma molécula hidrofóbica 21 que apresenta o éster oleato de etila em sua constituição. O produto 21 foi obtido com 75% de rendimento. As amidas fenólicas 12-21 produzidas neste trabalho são derivadas do ácido linoleico (ômega 6) e do ácido salicílico, os quais apresentam propriedades emolientes e antioxidantes. Estes compostos são interessantes para a formulação de produtos cosméticos de aplicação cutânea. Neste processo biotecnológico as reações foram conduzidas na ausência de solventes orgânicos, evitando o tratamento de solventes voláteis e a formação de subprodutos. Os compostos foram analisados por Cromatografia líquida de alta eficiência e caracterizados por RMN (1H, 13C), EMAR e IV. A aplicação de reações de biocatálise seja através de células microbianas ou de enzimas isoladas foram muito promissoras na síntese de compostos orgânicos de interesse como álcoois enantiomericamente puros ou amidas graxas. / In this work, alcohol dehydrogenase (ADHs) enzymes from marine fungi and immobilized lipase from Candida antarctica were employed for the production of compounds of biological and synthetic interest. In chapter 1, ADHs of fungi isolated from the marine alga Bostrychia radicans were used in reduction reactions of fluorinated ketones 1-5. The fungi identified as Botryosphaeria sp. CBMAI 1197, Eutypella sp. CBMAI 1196, Hidropisphaera sp. CBMAI 1194 and Xylaria sp. CBMAI 119 acted as biocatalysts in these reactions leading to production of alcohols with high enantiomeric purity. The fungus Botryosphaeria sp. CBMAI 1197 presented highlighted compared to other microorganisms producing the alcohols (S)-2,2,2-trifluoro-1-phenylethanol (1a) and (R) -1 - (2,4,5-trifluorophenyl) ethanol (3a) with excellent conversions (100% and 97%) and enantiomeric excesses (ee > 99%). This fungus also exhibited ADHs enzymes active with dicarbonylateds ketones, leading to the production of the alcohols 4,4,4-trifluoro-1-phenylbutane-1,3-diol (4a) and 4,4,4-trifluoro-1-(naphthalen-2-yl)butane-1,3-diol -1,3-butanediol (5a) with conversions of 100% in both cases and enantiomeric excess of 99%-97%, respectively. This was the first study conducted with dicarbonilated fluoroketones 4-5 and with fungi isolated from the marine alga Bostrychia radicans in Brazil. In chapter 2, immobilized lipase from Candida antarctica was used as biocatalyst in the aminolysis reaction between esters of ethyl linoleate (1) and ethyl salicylate (3), the fatty amine N-dodecylamine (2) and the aminoalcohols (4-8). Six aminoalcohols were selected for reactions with ethyl salicylate (3), where the lipase exhibited chemoselectivity by the amino groups, producing predominantly phenolic amides in yields of 23-63%. The CALB exhibited um reduction in chemoselectivity in the reaction with 5-aminopentanol (6) where the amide 14 and ester 15 products were obtained with 44% and 33% yields. The product 2-hydroxy-N-(2-hydroxypropyl) benzamide (19) was obtained in yield greater than 90% from the reaction catalyzed by lipase from Candida antarctica. This product was selected as reagente for the synthesis of a hydrophobic molecule 21 presenting ester ethyl oleate in its constitution. The product 21 was obtained in 75% yield. The phenolic amides 12-21 produced in this work are derived from linoleic acid (omega 6) and salicylic acid, which presents emollient and antioxidants properties. These compounds are interesting for the formulation of cosmetic products for skin application. In this biotechnological process, the reactions were carried out under solvent-free conditions and vacum, avoiding the treatment of volatile solvents and by-product formation. The compounds were analyzed by high performance liquid chromatography and characterized by NMR (1H, 13C), IR and HRMS. Applying biocatalysis reactions, either through microbial cells or isolated enzymes were promising for the synthesis of organic compounds such as enantiomerically pure alcohols and fatty phenolic amides.

L'isosorbide est un dianhydrohexitol chiral obtenu énantiomériquement pur par double déshydratation du sorbitol, un des produits majoritaires de l'industrie amidonnière résultant de l'hydrogénation du glucose. L'intérêt croissant pour l'isosorbide ces deux dernières décennies s'explique notamment grâce à sa production industrielle par des entreprises comme Roquette (20 000 tonnes par an). Cette disponibilité a permis la valorisation de l isosorbide dans divers domaines : polymères (polyéthylène isosorbide téréphtalate), tensioactifs, solvants (diméthyl isosorbide) et pharmaceutique (isosorbide dinitrate). Les propriétés de l'isosorbide ont ouvert la voie à des applications en induction chirale comme ligand, auxiliaire ou catalyseur par transfert de phase. D'autres isohexides (isomannide et isoidide) ont été moins étudiés. Leur structure conformationnelle rigide offre une grande diversité de modifications afin de moduler leurs propriétés électroniques et stériques. Les isohexides sont des candidats prometteurs pour le développement d'organocatalyseurs biosourcés. Très récemment, l'alkylation énantiosélective d'indole catalysée par des dérivés thiourées basées sur le squelette isohexide a été décrite. Au cours de cette thèse, la fonctionnalisation des isohexides en dérivés aminés est rapportée. La synthèse d'une première série d'amino-alcools, amino-éthers et diamines est décrite. Une seconde génération d'α-amino-amides et 1,2-diamines est obtenue par amidation. Ces dérivés aminés sont engagés comme organocatalyseurs dans la synthèse asymétrique de la warfarine (avec des résultats atteignant 20% de rendement et 28% d'e.e.) et l'aldolisation de l'isatine (jusqu'à 73% de rendement et 33% d'e.e.) / Isosorbide is a chiral dianhydrohexitol obtained in enantiomerically pure form by double dehydration of sorbitol, a major product of the starch industry resulting from hydrogenation of glucose. Isosorbide has been increasingly studied these last twenty years, mainly thanks to industrial companies, such as Roquette (France) that implemented the production to 20,000 tons a year. This availability allowed the promotion of isosorbide applications in various fields: polymers (polyethylene isosorbide terephthalate), surfactants, solvents (dimethyl isosorbide) and pharmacy (isosorbide dinitrate). Isosorbide structural properties opened its investigation as a chiral inducer either as a ligand, an auxiliary or a phase transfer catalyst. Other isohexides (isomannide, isoidide) were much less studied. These diastereomeric conformationally rigid structures offer a large diversity of functionalizations to tune their electronic and steric properties. Isohexides are promising candidates for the development of biosourced organocatalysts. Very recently, Friedel-Crafts enantioselective alkylation of indole mediated by thiourea organocatalysts derived from isohexides has been described. In this thesis, the functionalization of isohexides into amino derivatives is reported. A first serie of amino-alcohols, amino-ethers and diamines is reported. A second generation of α-amino amides and 1,2-diamines is then obtained via amidation. These nitrogenfunctionalized derivatives are screened as organocatalysts for the asymmetric synthesis of warfarin (with results up to 20% of yield and 28% of e.e.) and for isatin aldolisation (with results up to 73% of yield and 33% of e.e.)

Ces dernières années, les recherches industrielles et académiques ont connu des bouleversements sans précédents liés à la notion de Développement Durable. Les exigences en matière de santé et d’environnement ont poussé les chimistes à concevoir des produits et procédés chimiques qui permettent de réduire ou d’éliminer les substances dangereuses. Les travaux de recherche décrits dans cette thèse s’inscrivent dans ce contexte et concernent la mise au point de nouveaux systèmes réducteurs utilisant des hydrosiloxanes comme substituts des hydrures d’aluminium et de bore. Dans cet objectif, des systèmes associant le 1,1,3,3-tétraméthyldisiloxane (TMDS) ou le polyméthylhydrosiloxane (PMHS) avec des complexes de titane ou de vanadium ont été développés pour la réduction des fonctions amides et nitriles. La nature de l’association hydrosiloxane – métal et du substrat étudié a joué un rôle important sur la performance et la sélectivité des réactions misent en oeuvre. D’une part, les réductions sélectives d’amides (tertiaires et secondaires) et de nitriles en aldéhydes ont été réalisées respectivement en présence du tétraisopropylate de titane(IV) et du triisopropylate d’oxyde de vanadium(V). D’autre part, les réductions d’amides primaires et de nitriles ont conduit aux amines primaires en présence de tétraisopropylate de titane(IV). Enfin, ces systèmes réducteurs ont été utilisés pour la synthèse d’hétérocycles azotés saturés. La réduction de composés dinitriles donne lieu à une réaction d’alkylation réductrice intramoléculaire qui conduit à la formation de dérivés de la pipéridine, de la pyrrolidine et de l’azétidine en une étape / In recent years, industrial and academic researches have experienced unprecedented changes related to the concept of sustainable development. Health and environment new requirements have prompted chemists to develop chemical products and processes that reduce or eliminate hazardous substances. The research work described in this thesis is focused on the development of new reducing systems using hydrosiloxanes as substitutes for aluminum and boron hydrides. In order to achieve this goal, reducing systems combining 1,1,3,3-tetramethyldisiloxane (TMDS) or polymethylhydrosiloxane (PMHS) with titanium or vanadium complexes have been developed for the reduction of amides and nitriles. The nature of both the association “hydrosiloxane – metal” as well as the studied substrate played an important role on the performance and the selectivity of the reaction. On the one hand, selective reductions of amides (tertiary and secondary) and nitriles to aldehydes were carried out respectively in the presence of titanium(IV) tetraisopropoxide and vanadium(V) triisopropoxide oxide. On the other hand, reductions of amides (primary) and nitriles afforded the corresponding primary amines in the presence of titanium(IV) tetraisopropoxide. Finally, these systems have been applied for the synthesis of saturated N-heterocycles. Reduction of dinitrile compounds led, in one step, to piperidine, pyrrolidine and azetidine derivatives through an intramolecular reductive alkylation reaction

Notre étude a pour objet la conception, la synthèse ainsi que l’étude structurale d’architectures supramoléculaires obtenues par auto-assemblage, en se basant sur les concepts de la tectonique moléculaire. Cette branche de la chimie supramoléculaire s’occupe de la conception et la synthèse de molécules organiques appelées tectons, du grec tectos qui signifie constructeur. Le tecton est souvent constitué de sites de reconnaissance branchés sur un squelette bien choisi. Les sites de reconnaissance orientés par la géométrie du squelette peuvent participer dans des interactions intermoléculaires qui sont suffisamment fortes et directionnelles pour guider la topologie du cristal résultant. La stratégie envisagée utilise des processus d'auto-assemblage engageant des interactions réversibles entre les tectons. L’auto-assemblage dirigé par de fortes interactions intermoléculaires directionnelles est largement utilisé pour fabriquer des matériaux dont les composants doivent être positionnés en trois dimensions (3D) d'une manière prévisible. Cette stratégie peut également être utilisée pour contrôler l’association moléculaire en deux dimensions (2D), ce qui permet la construction de monocouches organisées et prédéterminées sur différents types des surfaces, tels que le graphite.Notre travail a mis l’accent sur le comportement de la fonction amide comme fonction de reconnaissance qui est un analogue du groupement carboxyle déjà utilisé dans plusieurs études précédentes. Nous avons étudié le comportement d’une série de composés contenant un noyau plat conçu pour faciliter l'adsorption sur le graphite et modifiés par l'ajout de groupes amide pour favoriser la formation de liaisons hydrogène entre les molécules ainsi adsorbées. La capacité de ces composés à former de monocouches organisées à l’échelle moléculaire en 2D a été examinée par microscopie à effet tunnel, etleur organisation en 3D a également été étudiée par cristallographie aux rayons X. Dans notre étude, nous avons systématiquement modifié la géométrie moléculaire et d'autres paramètres afin d'examiner leurs effets sur l'organisation moléculaire. Nos résultats suggèrent que les analyses structurales combinées en 2D et 3D constituent un important atout dans l'effort pour comprendre les interactions entre les molécules adsorbées et l’effet de l’interaction avec la surface du substrat. / Our study involves the design, synthesis and structural analysis of supramolecular architectures obtained by self-assembly, based on the concepts of molecular tectonics. This branch of supramolecular chemistry explores the properties of molecules called tectons,from the Greek word tectos, meaning builder. Tectons typically incorporate sites of recognition connected to well-chosen skeletons with defined geometries. The sites of recognition, oriented by the geometry of the skeleton, can participate in intermolecular interactions that are sufficiently strong and directional to control the topology of the resulting assembly. This strategy is thereby based on self-assembly processes involving reversible interactions between tectons. Self-assembly directed by strong directional intermolecular interactions is widely used to produce materials whose components must be positioned in three dimensions (3D) in a predictable way. This strategy can also be used to control molecular association in two dimensions (2D), thereby allowing the construction of predictably organized and predetermined nanopatterns on various surfaces, such as graphite.Our work has focused on the behavior of the amide groups as primary sites of intermolecular interaction. These groups are analogues of carboxyl groups, which have been widely used in previous studies of directed molecular assembly. We have studied the 3D and 2D association of compounds with flat cores designed to favor the formation of sheets and to facilitate adsorption on graphite, modified by the addition of amide groups to promote the formation of intermolecular hydrogen bonds. The ability of these compounds to form predictably ordered 2D nanopatterns has been examined by scanning tunneling microscopy, and their organization in 3D has also been investigated by X-ray crystallography. In our study, we have systematically altered molecular geometry and other parameters to examine their effect on molecular organization. Our results suggest that combined structural analyses in 2D and 3D are an important asset in the effort to understand why molecules aggregate in particular ways and how these preferences can be altered by underlying surfaces.

Ce travail de recherche a pour objectifs d’évaluer les activités antibactériennes, antiprolifératives et antioxydantes des extraits de feuilles de Solanum incanum L., S. schimperianum Hochst, S. nigrum L., Physalis lagascae Roem. & Schult. et Withania somnifera (L) Dunal. Plus précisément, les activités antibactériennes, anti-prolifératives et antioxydantes ont été déterminées à partir des extraits méthanoliques et des fractions de glycoalcaloïdes stéroïdiens (SGAF) de chaque plante. La sensibilité des bactéries, à Gram positif et à Gram négatif, était variable en présence de chacun des extraits (valeurs des IC50 dans la gamme de 15 > 1000 μg / mL). L'extrait méthanolique de la feuille de S. schimperianum a montré une activité anti-proliférative intéressante contre les lignées cellulaires humaines testées avec des valeurs de CI50 variant de 2,69 à 19,83 μg / mL tandis que l'activité la plus élevée des fractions de feuilles (SGAF) de W. somnifera a montré des valeurs IC50 variant de 1,29 à 5,00 μg / mL. Les fractions SGAF de toutes les espèces ont montré une activité antiradicalaire plus élevée que leurs extraits méthanoliques. La fraction SGAF de S. schimperianum a montré l'activité antioxydante la plus forte avec une valeur CI50 3,5 ± 0,2 μg / mL pour le test DPPH et 3,5 ± 0,3 μg / mL pour le test ABTS. L'analyse GC-MS des extraits méthanoliques et des fractions SGAF des espèces étudiées a révélé la présence d'alcaloïdes stéroïdiens, de saponines stéroïdiennes, de stéroïdes et d'autres composés comme des terpènes, des phénols et des alcanes. Leur répartition variait selon les espèces et, ce qui peut fournir des éléments pour évaluer les relations chimiotaxonomiques préliminaires. Douze dérivés de l'acide hydroxycinnamique ont été identifiés dans l'extrait méthanolique de la feuille de S. schimperianum et le composé N-caffeoyl agmatine était majoritaire. La présence d'alcaloïdes stéroïdiques comme la solanopubamine et la solanocapsine, ainsi que des dérivés des alcaloïdes 3-amino stéroïdes a été notée. De plus, trois composés, quercétine, kaempférol glycosylé et le β-sitostérol, ont été isolés et identifiés / This study aimed at the evaluation of in vitro antibacterial, antiproliferative and antioxidant activities of methanolic leaf extracts and steroidal glycoalkaloids fractions (SGAFs) of Solanum incanum L., S. schimperianum Hochst, S. nigrum L., Physalis lagascae Roem. & Schult. and Withania somnifera (L) Dunal. The sensitivity of Gram-positive and Gram-negative bacteria to each extract was variable (IC50 values in the range of 15->1000 µg/mL). The methanolic extract of S. schimperianum leaf demonstrated interesting anti-proliferative activity against the human cell lines tested with IC50 values in the range of 2.69 to 19.83 µg/mL while the highest activity from the SGAFs was obtained from W. somnifera leaf with IC50 values in the range of 1.29 to 5.00 µg/mL. The SGAFs of all species demonstrated higher scavenging activity than their respective methanolic extracts. The SGAF of S. schimperianum displayed the strongest antioxidant activity in both assays with IC50 value 3.5 ± 0.2DPPH and 3.5 ±0.3ABTS µg/mL. GC-MS analysis of methanolic and SGAFs extracts of the studied species revealed the presence of steroidal alkaloids, steroidal saponins, steroids and other compounds like terpenes, phenols and alkanes. Their distribution varied among the species and thus they could provide evidence to assess preliminary chemotaxonomic relationships. Twelve known hydroxycinnamic acid amides were tentatively identified from the methanolic extract of S. schimperianum leaf and N-caffeoyl agmatine appeared with the highest intensity. Moreover, the presence of steroid alkaloids solanopubamine and solanocapsine as well as dehydroderivatives of the 3-amino steroid alkaloids was suggested. Furthermore, three compounds quercetin, kaempferol glycoside and β-sitosterol were isolated and identified. In silico investigation of these three compounds for their potency against cancer revealed that β-sitosterol was found to be the most selective compound against human pregnane X receptor (PXR) and gave the highest binding energy (-11.2 kcal/mol). These results suggested that Solanaceae plants endogenous to Sudan could be a potential source of bioactive agents

Neste trabalho, enzimas álcool-desidrogenases provenientes de fungos marinhos e a lipase imobilizada de Candida antarctica foram utilizadas para produção de compostos de interesse sintético e biológico. No capítulo 1, enzimas álcool-desidrogenases de fungos isolados da alga marinha Bostrychia radicans foram empregadas em reações de redução de cetonas fluoradas 1-5. Os fungos identificados como Botryosphaeria sp. CBMAI 1197, Eutypella sp. CBMAI 1196, Hidropisphaera sp. CBMAI 1194 e Xylaria sp. CBMAI 119 atuaram como biocatalisadores nestas reações levando à produção de álcoois com elevada pureza enantiomérica. O fungo Botryosphaeria sp. CBMAI 1197 destacou-se frente aos demais microrganismos, produzindo os álcoois (S)-2,2,2-trifluoro-1-feniletanol (1a) e (R)-1-(2,4,5-trifluorofenil)etanol (3a) com excelentes conversões (100% e 97%) e excessos enantioméricos (ee >99%). Este fungo também apresentou enzimas álcool-desidrogenases ativas frente a cetonas dicarboniladas 4-5, produzindo os álcoois 4,4,4-trifluoro-1-fenil-1,3-butanodiol (4a) e 4,4,4-trifluoro-1-(2-naftalenil)-1,3-butanodiol (5a) com 100% de conversão em ambos os casos e com purezas enantioméricas respectivas a 99% e 97%. Este foi o primeiro estudo realizado no Brasil com fluorocetonas dicarboniladas e com os fungos isolados da alga marinha Bostrychia radicans. No capítulo 2, a lipase comercial de Candida antarctica foi o biocatalisador empregado em reações de aminólise entre os ésteres linoleato de etila (1) e salicilato de etila (3), a amina graxa N-dodecilamina (2) e os aminoálcoois (4-9). A amina graxa N-dodecilamina (2) também foi utilizada em reações com o linoleato de etila (1), onde a lipase de Candida antarctica produziu a respectiva amida graxa 10 com rendimentos superiores a 95%. Os aminoálcoois foram selecionados para reações com o salicilato de etila (3), onde a lipase exibiu quimiosseletividade pelo grupo amino, produzindo predominantemente amidas fenólicas (12-19) com rendimentos entre 23-68%. A enzima CALB apresentou quimiosseletividade reduzida na reação com o 5-aminopentanol (6) onde os produtos amida 14 e éster 15 foram obtidos com rendimentos de 44 e 33%, respectivamente. O produto 2-hidroxi-N-(2-hidroxipropil)benzamida (19) foi obtido com rendimento superior a 90% a partir da reação catalisada pela lipase de Candida antarctica. Este produto foi selecionado como intermediário para a síntese de uma molécula hidrofóbica 21 que apresenta o éster oleato de etila em sua constituição. O produto 21 foi obtido com 75% de rendimento. As amidas fenólicas 12-21 produzidas neste trabalho são derivadas do ácido linoleico (ômega 6) e do ácido salicílico, os quais apresentam propriedades emolientes e antioxidantes. Estes compostos são interessantes para a formulação de produtos cosméticos de aplicação cutânea. Neste processo biotecnológico as reações foram conduzidas na ausência de solventes orgânicos, evitando o tratamento de solventes voláteis e a formação de subprodutos. Os compostos foram analisados por Cromatografia líquida de alta eficiência e caracterizados por RMN (1H, 13C), EMAR e IV. A aplicação de reações de biocatálise seja através de células microbianas ou de enzimas isoladas foram muito promissoras na síntese de compostos orgânicos de interesse como álcoois enantiomericamente puros ou amidas graxas. / In this work, alcohol dehydrogenase (ADHs) enzymes from marine fungi and immobilized lipase from Candida antarctica were employed for the production of compounds of biological and synthetic interest. In chapter 1, ADHs of fungi isolated from the marine alga Bostrychia radicans were used in reduction reactions of fluorinated ketones 1-5. The fungi identified as Botryosphaeria sp. CBMAI 1197, Eutypella sp. CBMAI 1196, Hidropisphaera sp. CBMAI 1194 and Xylaria sp. CBMAI 119 acted as biocatalysts in these reactions leading to production of alcohols with high enantiomeric purity. The fungus Botryosphaeria sp. CBMAI 1197 presented highlighted compared to other microorganisms producing the alcohols (S)-2,2,2-trifluoro-1-phenylethanol (1a) and (R) -1 - (2,4,5-trifluorophenyl) ethanol (3a) with excellent conversions (100% and 97%) and enantiomeric excesses (ee > 99%). This fungus also exhibited ADHs enzymes active with dicarbonylateds ketones, leading to the production of the alcohols 4,4,4-trifluoro-1-phenylbutane-1,3-diol (4a) and 4,4,4-trifluoro-1-(naphthalen-2-yl)butane-1,3-diol -1,3-butanediol (5a) with conversions of 100% in both cases and enantiomeric excess of 99%-97%, respectively. This was the first study conducted with dicarbonilated fluoroketones 4-5 and with fungi isolated from the marine alga Bostrychia radicans in Brazil. In chapter 2, immobilized lipase from Candida antarctica was used as biocatalyst in the aminolysis reaction between esters of ethyl linoleate (1) and ethyl salicylate (3), the fatty amine N-dodecylamine (2) and the aminoalcohols (4-8). Six aminoalcohols were selected for reactions with ethyl salicylate (3), where the lipase exhibited chemoselectivity by the amino groups, producing predominantly phenolic amides in yields of 23-63%. The CALB exhibited um reduction in chemoselectivity in the reaction with 5-aminopentanol (6) where the amide 14 and ester 15 products were obtained with 44% and 33% yields. The product 2-hydroxy-N-(2-hydroxypropyl) benzamide (19) was obtained in yield greater than 90% from the reaction catalyzed by lipase from Candida antarctica. This product was selected as reagente for the synthesis of a hydrophobic molecule 21 presenting ester ethyl oleate in its constitution. The product 21 was obtained in 75% yield. The phenolic amides 12-21 produced in this work are derived from linoleic acid (omega 6) and salicylic acid, which presents emollient and antioxidants properties. These compounds are interesting for the formulation of cosmetic products for skin application. In this biotechnological process, the reactions were carried out under solvent-free conditions and vacum, avoiding the treatment of volatile solvents and by-product formation. The compounds were analyzed by high performance liquid chromatography and characterized by NMR (1H, 13C), IR and HRMS. Applying biocatalysis reactions, either through microbial cells or isolated enzymes were promising for the synthesis of organic compounds such as enantiomerically pure alcohols and fatty phenolic amides.

This work presents an in-depth study of the crystal structures and hydrogen sorption potential of the Li - N - H and Li - Na - N - H systems. The structures of the materials have been studied using X-ray and neutron diffraction, Raman spectroscopy and inelastic neutron scattering. The behavior of the materials during heating was studied using variable temperature X-ray diffraction, intelligent gravimetric analysis in conjunction with neutron diffraction, intelligent gravimetric analysis combined with mass spectrometry and differential scanning calorimetry. The role of cation disorder in the Li - N - H (D) system has been explored, indicating that crystallographic ordering of the Li⁺ ions within lithium amide and lithium imide significantly affects the hydrogen sorption properties of the materials. Order-disorder transitions were observed both during hydrogen desorption from ordered LiNH₂ and during deuterium adsorption on ordered Li₂ND. Such transitions were not observed in disordered samples of the materials. The intrinsic disorder and the stoichiometry of Li - N - H(D) materials was shown to depend strongly on the techniques used during their synthesis. Studies regarding the synthesis, crystal chemistry and decomposition properties of the mixed Li / Na amides are presented. Two distinct mixed Li / Na amides of formulae Li₃Na(NH₂)₄ and LiNa₂(NH₂)₃ were observed in the LiNH₂ / NaNH₂ phase space. Na was also seen to be soluble in LiNH₂, forming sodium-doped LiNH₂ . Li₃Na(NH₂)₄ and Na-doped LiNH₂ were found to exhibit significant cation non-stoichiometry, whereas LiNa₂(NH₂)₄ was shown to exist as a line phase material. Thermogravimetric and calorimetric studies of the mixed Li / Na amides suggested that these materials decompose primarily with loss of H₂.

O extrato bruto (DCM:MeOH 2:1) das raízes de Piper crassinervium foi submetido a fracionamentos cromatográficos resultando no isolamento e identificação de oito substâncias, sendo estas uma flavanona (5,4\'-diidroxi-7-metoxiflavanona [isosakuranetina]), duas hidroquinonas preniladas (1,4-diidroxi-2-[3\',7\'-dimetil-1\'-oxo-2\'-E-6\'-octadienil]-benzeno e 1,4-diidroxi-2-[3\',7\'-dimetil-1\'-oxo-2\'-Z-6\'-octadienil]-benzeno), um cromeno (ácido-2-metil-2-[4\'-metil-3\'-pentenil]2H-1-benzopirano-6-carboxílico), um derivado prenilado do ácido benzóico (ácido 4-hidroxi-3-[3\',7\'-dimetil-1\'-oxo-octa-2\'-E-6\'-dienil]-benzóico), uma amida isobutílica (piperlonguminina) e duas amidas piperidínicas (piperina e diidropiperina). As substâncias isoladas tiveram suas estruturas químicas determinadas por experimentos de espectrometria de massas, RMN de 1H e 13C e comparadas com os dados da literatura. / The crude extracts of the roots of Piper crassinervium was submitted to chromatographic steps yielding eight compounds including a flavanone (5,4\'-dihydroxy-7-methoxyflavanone [isosakuranetin]), two prenylated hydroquinones (1,4-dihydroxy-2-[3\',7\'-dimethyl-1\'-oxo-2\'-E-6\'-octadienyl]-benzene and 1,4-dihydroxy-2-[3\',7\'-dimethyl-1\'-oxo-2\'-Z-6\'-octadienyl]-benzene), one chromene (2-methyl-2-[4\'-methyl-3\'-pentenyl]-2H-1-benzopyran-6-carboxylic acid), one prenylated derivative of benzoic acid (4-hydroxy-3-[3\',7\'-dimethil-1\'-oxo]2\'-E-6\'-octadienyl-benzoic acid), one isobutyl amide (piperlonguminine) and two piperidine amides (piperine and dihydropiperine). The structures of the isolated compounds were determined by mass spectrometry, 1H and 13C NMR data by comparison with the literature data.

Dans le cadre du développement de nouveaux procédés par extraction liquide-liquide pour le recyclage du combustible nucléaire usé, de nouvelles molécules extractantes sont à l’étude. Les molécules à fonction amide (monoamide, malonamide ou diglycolamide) sont particulièrement étudiées. Les objectifs de cette thèse sont d’étudier la spéciation moléculaire et supramoléculaire de solutions organiques représentatives des différents procédés en cours de développement. Cette spéciation a été réalisée en couplant des études expérimentales et théoriques. Après extraction de solutés, la composition des solutions organiques est déterminée expérimentalement. Des boites de simulation par dynamique moléculaire ayant la même composition que les solutions expérimentales sont ensuite construites. Après simulation, les trajectoires de dynamique moléculaire permettent de calculer les masses volumiques et les intensités diffusées aux petits angles théoriques des solutions simulées. Dès lors que les données calculées et les données expérimentales sont en accord, on estime que les simulations sont représentatives des solutions réelles. Ces simulations couplées à des caractérisations expérimentales supplémentaires (spectroscopie infra-rouge – IR – et spectrométrie de masse à ionisation par électrospray – ESI-MS –) permettent de décrire les structures en solution à la fois à l’échelle moléculaire et supramoléculaire. Cette méthodologie a été appliquée à l’extraction d’eau et de nitrate d’uranyle par les monoamides DEHBA et par le malonamide DMDOHEMA ainsi qu’à l’extraction d’eau et de nitrate de néodyme par des solutions à base de TODGA.L’extraction d’eau en phase organique est dépendante de l’organisation de la solution : les solutions de monoamides essentiellement constituées de monomères et dimères solubilisent peu d’eau contrairement aux solutions de DMDOHEMA ou de TODGA majoritairement constituées d’agrégats. L’extraction de nitrate d’uranyle a mis en évidence différents comportements dépendant de la structure de la molécule ou de la concentration d’uranyle. Des complexes UO2(NO3)2L2 sont observés à faible concentration d’uranium après extraction par les monoamides. Lorsque la concentration d’uranium augmente, des espèces polymétalliques sont observées et deviennent majoritaire en solution. Dans le cas du DMDOHEMA, des complexes monométalliques sont majoritaires mais n’ont pas une stœchiométrie unique. L’uranyle peut être coordiné à 1 ou 2 malonamides (monodenté ou bidenté), 2 nitrates et parfois une molécule d’eau. Le néodyme est extrait par le TODGA dans l’heptane sous forme de petits agrégats contenant 2 ou 3 cations liés par des nitrates pontants. Une augmentation de la concentration de néodyme entraine une augmentation de l’agrégation jusqu’à l’apparition d’une démixtion de phase. La présence d’octanol (0,3 mol/L) permet d’extraire une plus forte concentration de Nd sans séparation de phase. Les simulations ont montré que l’octanol se place dans la 1ère sphère de coordination du néodyme à la place des molécules d’eau ou de TODGA améliorant ainsi la solubilité des complexes et agrégats dans la phase organique. L’ajout de 0,5 mol/L de DMDOHEMA à une solution de TODGA permet également d’éviter la démixtion en structurant la solution. En présence de malonamide des agrégats plus petits sont observés.Pour les deux systèmes étudiés (mono et diamides), les phases obtenues après démixtion de la phase organique (phénomène de formation de 3ème phase) ont également été caractérisées.Ces travaux ont permis de déterminer l’organisation moléculaire et supramoléculaire dans des solutions d’extraction par l’utilisation d’une méthode couplant études expérimentales et simulations par dynamique moléculaire. / In the framework of development of new processes for spent nuclear fuel reprocessing, new extractant molecules are studied.The goals of this thesis are to study the molecular and supramolecular speciation of representative organic solutions. The speciation was determined by coupling experimental and theoretical study. After solute extraction, the composition of the organic solutions is experimentally determined. Simulations boxes with the same composition than experimental solutions are build. After simulation, trajectories are used to calculate small angle scattered intensities. The representativeness of the simulations is checked by comparison of experimental and calculated scattered intensities. The use of the simulation, ESI-MS spectrometry and IR spectroscopy provides the description of the structures in organic solution at the molecular and supramolecular scale. This methodology was applied on water and uranyl nitrate extraction by the monoamide DEHBA and MOEHA and by the malonamide DMDOHEMA as well as the extraction of water and neodymium nitrate by TODGA solutions.The extraction of water is dependent of the organization of the solution: monoamide solution made of monomer and dimer solubilize few amount of water in comparison with DMDOHEMA or TODGA solutions.The extraction of uranyl nitrate showed different behavior. UO2(NO3)2L2 complexes are observed at low uranium concentration after extraction by the monoamides. Polymetallic species are observed with the increase of uranium concentration. In the case of DMDOHEMA, monometallic complexes are majority but without a unique stoichiometry. The uranyl can be linked to 1 o 2 malonamides, 2 nitrates and sometimes to a water molecule. Neodymium is extracted by TODGA within small aggregates made of 2 or 3 cations liked by bridging nitrates. The increase of the concentration of neodymium leads to a phase separation. The presence of octanol provides the extraction of higher concentration of neodymium nitrate. Simulations showed the replacement of water and TODGA molecules and the first coordination sphere of the cation with octanol molecule. This increases the solubility of the aggregates. The presence of DMDOHEMA prevents also the phase separation by structuring the solution. With malonamide, smaller aggregates are observed.For both systems, phases after demixing (third phase formation) were characterized.This work provides the study of the molecular and supramolecular organization of organic solutions by combining experimental studies and molecular dynamic simulations.