O petróleo é a principal fonte de energia no mundo, mas alguns de seus derivados podem ser prejudiciais à natureza e à saúde. O BTEX, um derivado do petróleo, é usado em combustíveis, sendo estes a maior causa de contaminação ambiental, pois no transporte ou armazenamento destes ocorrem vazamentos que poluem solo e fontes de água. Como alternativas para diminuir a concentração do BTEX no combustível surgiram os aditivos oxigenados, os quais melhoram a qualidade do combustível e reduzem as emissões de monóxido de carbono. Os aditivos mais comuns são o MTBE e o etanol. No entanto, o MTBE é oncogênico e por isso, alguns países o substituem pelo etanol. Porém, o etanol aumenta a solubilidade do BTEX na água, a migração deste no solo, e diminui sua degradação natural. A degradação destes compostos é possível pela ação de microrganismos nativos. Em vista disto, no presente trabalho, bactérias foram isoladas de uma planta de tratamento de águas residuais da indústria petroquímica, com o objetivo de encontrar bactérias tolerantes com capacidade de degradação do BTEX. Os 30 isolados obtidos foram identificados como pertencentes aos gêneros Bacillus, Enterococcus, Staphylococcus, Streptococcus, Pseudomona, Lysinobacterium, Neisseria, Corynobacterium e Leucobacter. Quinze isolados foram tolerantes ao B, T, E, X, e destes, os isolados 16 e 25 pertencentes ao gênero Bacillus, foram testados para a degradação de BTEX, BTEX/MTBE, BTEX/Etanol. A maior porcentagem de degradação foi detectada no tratamento com BTEX seguido por BTEX/MTBE e BTEX/Etanol. O isolado 25 mostrou maior capacidade de degradação dos compostos. / Oil is the main source of energy in the world; nevertheless, some of its derivatives could be harmful to the environment and health. BTEX is a petroleum derivative. It is used in fuels; this one is the main cause of environmental pollution, because during the transport or storage of them there are leaks that pollute the soil and water sources. In order to reduce BTEX concentration in fuel, oxygenated additives emerged; these improve the quality of the fuel and reduce carbon monoxide emissions. The most common additives are MTBE and ethanol. Due to fact that MTBE is oncogenic, some countries replace it with ethanol. Ethanol increases the solubility of BTEX in water, its migration in the ground and decreases its natural degradation. The degradation of harmful compounds by action of native microorganisms has proven to be effective. With this purpose, in the current research, bacteria were isolated from a wastewater treatment plant of petrochemical industry, in order to find tolerant bacteria and with ability to degrade BTEX. The 30 isolates obtained were identified as belonging to the genus Bacillus, Enterococcus, Staphylococcus, Streptococcus, Pseudomonas, Lysinobacterium, Neisseria, Corynobacterium, and Leucobacter. Fifteen isolates were tolerant to B, T, E, X, and out them, isolates 16 and 25 belong to genus Bacillus were tested for degradation of BTEX BTEX / MTBE, BTEX / Ethanol. The highest percentage of degradation was found in the assay with BTEX followed by BTEX / MTBE and BTEX / Ethanol. Isolate 25 showed the highest capacity of degradation.

O petróleo é a principal fonte de energia no mundo, mas alguns de seus derivados podem ser prejudiciais à natureza e à saúde. O BTEX, um derivado do petróleo, é usado em combustíveis, sendo estes a maior causa de contaminação ambiental, pois no transporte ou armazenamento destes ocorrem vazamentos que poluem solo e fontes de água. Como alternativas para diminuir a concentração do BTEX no combustível surgiram os aditivos oxigenados, os quais melhoram a qualidade do combustível e reduzem as emissões de monóxido de carbono. Os aditivos mais comuns são o MTBE e o etanol. No entanto, o MTBE é oncogênico e por isso, alguns países o substituem pelo etanol. Porém, o etanol aumenta a solubilidade do BTEX na água, a migração deste no solo, e diminui sua degradação natural. A degradação destes compostos é possível pela ação de microrganismos nativos. Em vista disto, no presente trabalho, bactérias foram isoladas de uma planta de tratamento de águas residuais da indústria petroquímica, com o objetivo de encontrar bactérias tolerantes com capacidade de degradação do BTEX. Os 30 isolados obtidos foram identificados como pertencentes aos gêneros Bacillus, Enterococcus, Staphylococcus, Streptococcus, Pseudomona, Lysinobacterium, Neisseria, Corynobacterium e Leucobacter. Quinze isolados foram tolerantes ao B, T, E, X, e destes, os isolados 16 e 25 pertencentes ao gênero Bacillus, foram testados para a degradação de BTEX, BTEX/MTBE, BTEX/Etanol. A maior porcentagem de degradação foi detectada no tratamento com BTEX seguido por BTEX/MTBE e BTEX/Etanol. O isolado 25 mostrou maior capacidade de degradação dos compostos. / Oil is the main source of energy in the world; nevertheless, some of its derivatives could be harmful to the environment and health. BTEX is a petroleum derivative. It is used in fuels; this one is the main cause of environmental pollution, because during the transport or storage of them there are leaks that pollute the soil and water sources. In order to reduce BTEX concentration in fuel, oxygenated additives emerged; these improve the quality of the fuel and reduce carbon monoxide emissions. The most common additives are MTBE and ethanol. Due to fact that MTBE is oncogenic, some countries replace it with ethanol. Ethanol increases the solubility of BTEX in water, its migration in the ground and decreases its natural degradation. The degradation of harmful compounds by action of native microorganisms has proven to be effective. With this purpose, in the current research, bacteria were isolated from a wastewater treatment plant of petrochemical industry, in order to find tolerant bacteria and with ability to degrade BTEX. The 30 isolates obtained were identified as belonging to the genus Bacillus, Enterococcus, Staphylococcus, Streptococcus, Pseudomonas, Lysinobacterium, Neisseria, Corynobacterium, and Leucobacter. Fifteen isolates were tolerant to B, T, E, X, and out them, isolates 16 and 25 belong to genus Bacillus were tested for degradation of BTEX BTEX / MTBE, BTEX / Ethanol. The highest percentage of degradation was found in the assay with BTEX followed by BTEX / MTBE and BTEX / Ethanol. Isolate 25 showed the highest capacity of degradation.

Unilateral cortisol producing adenoma (CPA) is the most common cause of ACTH-independent Cushing’s syndrome and is surgically curable. On the other hand, adrenocortical carcinomas (ACCs) are rare and aggressive tumours. Although the overall survival of the patients with ACC is very poor, the outcome can be heterogeneous and vary significantly between the patients. This thesis comprises studies showing genetic and genomic events occurring in CPAs and ACCs, their functional impact and clinical correlations. The Wnt/β-catenin and cAMP/PKA signalling pathways are crucial in adrenal homeostasis and frequent mutations in members of these pathways (CTNNB1, GNAS, and PRKACA) are found in CPAs. Mutational analysis revealed that ~60% of the CPAs harboured mutations in either of these genes. Transcriptome signature exhibited increased expression of genes involved in steroidogenesis in PRKACA/GNAS mutated (Cluster1) tumours in comparison to CTNNB1 mutated /wildtype (Cluster2) tumours. In addition we have also observed that gain of chromosome arm 9q was the most frequent arm level copy number variation (CNV) occurring in CPAs and were exclusively present in Cluster2 tumours. We also discovered novel PRKACA mutations occurring in ACCs, causing activation of cAMP/signalling pathway.    Comprehensive analysis of Wnt/β-catenin signalling pathway in ACCs revealed novel interstitial deletions occurring in CTNNB1 leading to deletion of the N-terminus of β-catenin. This is a novel and yet another frequent event leading to activated Wnt/β-catenin signalling and downstream targets in ACCs. Both, mutations occurring in CTNNB1 and nuclear expression of its protein were associated with poor overall survival. Through multiregional sampling approach we discovered intra-tumour heterogeneity in ACC tumours. Although all the multiregions within a tumour showed presence of shared basal CNVs, they encompassed private CNVs, different ploidy levels and private mutations in known driver genes. We found intra-tumour heterogeneity in CTNNB1, PRKACA, TERT promoter and TP53 mutations as well as ZNRF3 and CDKN2A/2B homozygous deletions.

This work reports a novel biocompatible and biodegradable arborescent amphiphilic polypept(o)ides-based polymer poly(γ-benzyl L-glutamate)-co-poly(γ-tert-butyl L-glutamate)-g-polysarcosine (P(BG-co-Glu(OtBu))-g-PSar) as a smart dual-responsive targeting drug vehicle. The synthesis pathway in this work highlighted the grafting reaction improvement of the polypeptides core and using polysarcosine (PSar) corona as a coating agent. The responsiveness of the polymer is caused by the pH sensitivity of the polypeptides and the reducible linker introduced between the core and corona. While adding the tripeptides arginine, glycine, and aspartate (RGD) as a ligand on the unimolecular micelles’ surface increases the targeting ability of the polymer. During the building of the arborescent, the coupling sites were controlled by using γ-tert-butyl L-glutamate (Glu(OtBu)-NCA) as a second monomer besides γ-benzyl L-glutamate (BG-NCA) since the deprotection conditions are different for Bz and tBu groups. Knowing the coupling sites provides accuracy in calculating the molecular weight (MW) of graft polymers since it facilitates the determination of the grafting yield (Gy). The arborescent unimolecular micelles were formulated by coating the hydrophobic core with PSar hydrophilic corona. The distribution of the coupling sites on the substrates in the last generation yielded end-grafted and randomly-grafted unimolecular micelles. A comparison between those micelles by DLS, TEM, and AFM revealed that the end-grafted micelles showed more uniformity in terms of morphology and size distribution. Also, the surface modification achieved via RGD addition increased the shape uniformity and contributed to avoiding the particles’ aggregation. The sizes and shapes of end-grafted unimolecular micelles match the drug delivery systems (DDSs) requirements. Doxorubicin (DOX) was encapsulated physically into the unimolecular micelles to study the drug loading capacity (DLC) and drug loading efficiency (DLE). The maximum DLC and DLE were 14% and 28% w/w, respectively. The drug release profiles were investigated in healthy- and cancer-mimicking media. The results showed that in cancer-mimicking microenvironment (low pH and high glutathione (GSH) content), the drug diffused out the micelles faster. In addition, a slower drug release was noticed for RGD decorated unimolecular micelles. Finally, the biocompatibility, cytotoxicity, and cellular uptake of the unimolecular micelles were studied. The obtained results were promising as the arborescent unimolecular micelles showed excellent biocompatibility; meanwhile, the DOX-loaded unimolecular micelles have good cytotoxicity compared to free DOX. RGD targeting ligand contributes to increasing the cellular uptake and supports the sustained release.

[pt] Neste trabalho foi desenvolvida a síntese de novos análogos do tipo N-tosil-aza-carbapterocarpanos com potencial ação antiproliferativa em linhagens de leucemia e mama.Os compostos aza-carbapterocarpanos e espiro-iso-indolinas, foram preparados através de abordagens sintéticas distintas e classificadas em Grupo I e II respectivamente. A etapa chave para obtenção dos compostos do grupo I foi a reação de aza-arilação do tipo Heck catalisada por paládio a partir de tetralonas comerciais e N-tosil-iodoanilinas substituídas previamente sintetizadas. Três moléculas deste grupo foram avaliadas quanto a sua ação antiproliferativa em linhagens de leucemia e mama. Dentre estas, o composto N-tosil-aza-carbaptercarpeno apresentou IC50 = 1,93 (mais ou menos) 0,88 micrômetros, 2,18 (mais ou menos) 1,47 micrômetros e 2.89 (mais ou menos) 0,92 micrômetros nas linhagens de leucemia K562, lucena-1 e FEPS, respectivamente, e na linhagem de mama MDA-MB-231 IC50=33.37 (mais ou menos) 3.98 micrômetros. Por outro lado, o composto aza-carbapterocarpeno foi inativo nestas mesmas linhagens, indicando que na ausência do grupo arilsulfonamida a ação antileucêmica não ocorre. Os compostos do grupo II, denominados espiro iso-indolinas, foram sintetizados através da adição diastereosseletiva de organomagnesío às N-terc-butano-sulfiniliminas quirais, seguida de uma aminação de Buchwald-Hartwig intramolecular catalisada por paládio. As N-terc-butano-sulfiniliminas foram obtidas através de tetralonas, cromanonas e tiocromanonas comerciais em uma reação de condensação com as N-tert-butanosulfinamidas comerciais em micro-ondas em uma abordagem livre de solvente utilizando tetraetóxido de titânio. Após as reações de adição nucleofílica com organomagnésio, remoção do auxiliar quiral e ciclização intramolecular, os compostos forma obtidos enantiomericamente puros e foram avaliados em linhagens de leucemia K562 e FESP. Embora estes compostos tenham apresentado baixa potência frente às linhagens testadas (IC50 entre 31,85 mais ou menos 3.0 micrômetros e 77,58 (mais ou menos) 5.76 micrômetros), pôde-se observar que há diferenças relevantes entre os enantiômeros, assim o como apresentam sensibilidade colateral, atuando em linhagens multiresitentes. / [en] In this work, the synthesis of new N-tosyl aza-carbapterocarpane analogues with potential antiproliferative action in leukemia and breast cell lines was developed. The aza-carbapterocarpanes and spiro-isoindolines compounds were prepared using different synthetic approaches and classified in Group I and II respectively. The key step for obtaining group I compounds was the palladium catalyzed Heck-type azaarylation reaction from commercially synthesized substituted tetralones and substituted N-tosyl iodoanilines. Three compounds of this group were evaluated for their antiproliferative action in leukemia cell lines and breast cancer cells lines. The compound N-tosyl-aza-carbaptercarpene presented IC50 = 1,93 0,88 , 2,18 (plus or minus) 1,47 micrometers e 2.89 (plus or minus) 0,92 micrometers. On the other hand, the aza-carbapterocarpene compound was inactive in these same lines, suggesting the role of the absence of the arylsulfonamide group for the antileukemic activity does not occur .The group II, denominated spiroisoindolines, were synthesized by diastereoselective addition of organomagnesium to chiral N-tert-butane sulfinylimines, followed by a palladium catalyzed intramolecular Buchwald-Hartwig amination. The N-tert-butane sulfinylimines were obtained through commercial tetralones, chromanones and thiochromanones by the condensation reaction with commercial N-tert-butanesulfinamides in a solvent free sistem using titanium tetraethoxide. After nucleophilic addition reactions with organomagnesium, chiral auxiliary removal and intramolecular cyclization, the compounds were obtained enantiomerically pure and were evaluated in K562 and FESP leukemia lines. Although these compounds presented low potency compared to the tested lines (IC50 between 31.85 (plus or minus) 3.0 micrometers and 77.58 (plus or minus) 5.76 micrometers), it was observed that there of them present relevant differences between enantiomers as soon as collateral sensitivity, acting in leukemia multiresistent cell lines.

Nous avons démontré l’utilité du groupement protecteur tert-butylsulfonyle (N-Bus) pour la chimie des acides aminés et des peptides. Celui-ci est préparé en deux étapes, impliquant la réaction d’une amine avec le chlorure de tert-butylsulfinyle, suivie par l’oxydation par du m-CPBA, pour obtenir les tert-butylsulfonamides correspondants avec d’excellents rendements. Le groupement N-Bus peut être clivé par traitement avec 0.1 N TfOH/DCM/anisole à 0oC en 10h pour régénérer le sel d’ammonium. Une variété d’acides aminés N-Bus protégés ainsi que d’autres aminoacides peuvent alors être utilisés pour préparer divers dipeptides et tripeptides. A l’exception du groupe N-Fmoc, les conditions de déprotection du groupe N-Bus clivent également les groupements N-Boc, N-Cbz et O-Bn. Une déprotection sélective et orthogonale des groupes N-Boc, N-Cbz, N-Fmoc et O-Bn est également possible en présence du groupe protecteur N-Bus. Le nouvel acide aminé non-naturel (3R, 2R) 3–méthyl-D-leucine (β-Me-Leu) et son régioisomère 2-méthyle ont été synthétisés par ouverture d’une N-Ts aziridine en présence d’un excès de LiMe2Cu. Chacun des régioisomères du mélange (1:1,2) a été converti en la méthylleucine correspondante, puis couplé à l’acide D-phényllactique puis au motif 2-carboxyperhydroindole 4-amidinobenzamide en présence de DEPBT. Des élaborations ultérieures ont conduit à des analogues peptidiques non-naturels d’aeruginosines telles que la chlorodysinosine A. Les deux analogues ont ensuite été évalués pour leur activité inhibitrice de la thrombine et la trypsine. La présumée aeruginosine 3-sulfate 205B et son anomère β ont été synthétisés avec succès à partir de 5 sous-unités : la 3-chloroleucine, l’acide D-phényllactique, le D-xylose, le 2-carboxy-6-hydroxyoctahydroindole et l’agmatine. La comparaison des données RMN 1H et 13C reportées avec celles obtenues avec l’aeruginosine synthétique 205B révèle une différence majeure pour la position du groupe présumé 3'-sulfate sur l’unité D-xylopyranosyle. Nous avons alors synthétisés les dérivés méthyl-α-D-xylopyranosides avec un groupement sulfate à chacune des positions hydroxyles, afin de démontrer sans ambiguïté la présence du sulfate en position C-4' par comparaison des données spectroscopiques RMN 1H et 13C. La structure de l’aeruginosine 205B a alors été révisée. Une des étapes-clés de cette synthèse consiste en la formation du glycoside avec le groupe hydroxyle en C-6 orienté en axial sur la sous-unité Choi. Le 2-thiopyridylcarbonate s’est avéré une méthode efficace pour l’activation anomérique. Le traitement par AgOTf et la tétraméthylurée en solution dans un mélange éther-DCM permet d’obtenir l’anomère α désiré, qui peut alors être aisément séparé de l’anomère β par chromatographie / We have demonstrated the usefulness of tert-butylsulfonyl (N-Bus) protecting group in amino acid and peptide chemistry. It is formed in a 2-step procedure involving reaction of an amine with tert-butylsulfinyl chloride, followed by oxidation with m-CPBA to obtain the corresponding tert-butyl- sulfonamides in excellent yields. The N-Bus group can be cleaved to regenerate the corresponding amino salt in 0.1 N TfOH/DCM/anisole at 0 oC for 10 h. A variety of N-Bus protected amino acids and other common amino acids can be used to form dipeptides and tripeptides. With the exception of the N-Fmoc group, the conditions required for the N-Bus group cleavage also cleaved the N-Boc, N-Cbz and O-Bn groups. Selective and orthogonal deprotection of N-Boc, N-Cbz, N-Fmoc and O-Bn groups could be achieved in the presence of the N-Bus protecting group. The new unnatural amino acids (3R, 2R) 3–methyl-D-leucine (β-Me-Leu) and its 2-methyl regioisomer were synthesized by ring opening of an N-Ts aziridine intermediate with excess LiMe2Cu. The 1:1.2 mixture of regioisomers were each converted to the corresponding methyl leucines, then coupled to D-phenyllactic acid, followed by coupling with 2-carboxyperhydroindole 4-amidino-benzamide core in the presence of DEPBT. Further elaboration led to linear peptidic unnatural analogues of known aeruginosins such as chlorodysinosin A. The two analogues were also evaluated in enzymatic assays for their inhibitory activity against thrombin and trypsin. The presumed 3-sulfated aeruginosin 205B and its β–anomer were successfully synthesized from 5 subunits: 3-chloroleucine, D-phenyllactic acid, D-xylose, 2-carboxy-6-hydroxyoctahydroindole, and agmatine. Comparison of 1H and 13C NMR reported data with that of synthetic aeruginosin 205B revealed a disturbing discrepancy with regard to the position of the presumed 3'-sulfate on the D-xylopyranosyl unit. We synthesized methyl α-D-xylopyranosides with sulfates at each of the hydroxyl groups and conclusively demonstrated the the presence of a C-4'-sulfate by comparison of the 1H and 13C NMR spectroscopic data. Thus, the structure of aeruginosin 205B should be revised. One of the key steps in the synthesis is glycoside formation of the axially oriented C-6 hydroxyl group in the Choi subunit. The 2-thiopyridyl carbonate was a suitable method for anomeric activation, followed by treatment with AgOTf and tetramethylurea in ether-DCM solution to give the desired α-anomer, which was easily separable from the β-anomer by column chromatography.

No description available.

Nous avons démontré l’utilité du groupement protecteur tert-butylsulfonyle (N-Bus) pour la chimie des acides aminés et des peptides. Celui-ci est préparé en deux étapes, impliquant la réaction d’une amine avec le chlorure de tert-butylsulfinyle, suivie par l’oxydation par du m-CPBA, pour obtenir les tert-butylsulfonamides correspondants avec d’excellents rendements. Le groupement N-Bus peut être clivé par traitement avec 0.1 N TfOH/DCM/anisole à 0oC en 10h pour régénérer le sel d’ammonium. Une variété d’acides aminés N-Bus protégés ainsi que d’autres aminoacides peuvent alors être utilisés pour préparer divers dipeptides et tripeptides. A l’exception du groupe N-Fmoc, les conditions de déprotection du groupe N-Bus clivent également les groupements N-Boc, N-Cbz et O-Bn. Une déprotection sélective et orthogonale des groupes N-Boc, N-Cbz, N-Fmoc et O-Bn est également possible en présence du groupe protecteur N-Bus. Le nouvel acide aminé non-naturel (3R, 2R) 3–méthyl-D-leucine (β-Me-Leu) et son régioisomère 2-méthyle ont été synthétisés par ouverture d’une N-Ts aziridine en présence d’un excès de LiMe2Cu. Chacun des régioisomères du mélange (1:1,2) a été converti en la méthylleucine correspondante, puis couplé à l’acide D-phényllactique puis au motif 2-carboxyperhydroindole 4-amidinobenzamide en présence de DEPBT. Des élaborations ultérieures ont conduit à des analogues peptidiques non-naturels d’aeruginosines telles que la chlorodysinosine A. Les deux analogues ont ensuite été évalués pour leur activité inhibitrice de la thrombine et la trypsine. La présumée aeruginosine 3-sulfate 205B et son anomère β ont été synthétisés avec succès à partir de 5 sous-unités : la 3-chloroleucine, l’acide D-phényllactique, le D-xylose, le 2-carboxy-6-hydroxyoctahydroindole et l’agmatine. La comparaison des données RMN 1H et 13C reportées avec celles obtenues avec l’aeruginosine synthétique 205B révèle une différence majeure pour la position du groupe présumé 3'-sulfate sur l’unité D-xylopyranosyle. Nous avons alors synthétisés les dérivés méthyl-α-D-xylopyranosides avec un groupement sulfate à chacune des positions hydroxyles, afin de démontrer sans ambiguïté la présence du sulfate en position C-4' par comparaison des données spectroscopiques RMN 1H et 13C. La structure de l’aeruginosine 205B a alors été révisée. Une des étapes-clés de cette synthèse consiste en la formation du glycoside avec le groupe hydroxyle en C-6 orienté en axial sur la sous-unité Choi. Le 2-thiopyridylcarbonate s’est avéré une méthode efficace pour l’activation anomérique. Le traitement par AgOTf et la tétraméthylurée en solution dans un mélange éther-DCM permet d’obtenir l’anomère α désiré, qui peut alors être aisément séparé de l’anomère β par chromatographie / We have demonstrated the usefulness of tert-butylsulfonyl (N-Bus) protecting group in amino acid and peptide chemistry. It is formed in a 2-step procedure involving reaction of an amine with tert-butylsulfinyl chloride, followed by oxidation with m-CPBA to obtain the corresponding tert-butyl- sulfonamides in excellent yields. The N-Bus group can be cleaved to regenerate the corresponding amino salt in 0.1 N TfOH/DCM/anisole at 0 oC for 10 h. A variety of N-Bus protected amino acids and other common amino acids can be used to form dipeptides and tripeptides. With the exception of the N-Fmoc group, the conditions required for the N-Bus group cleavage also cleaved the N-Boc, N-Cbz and O-Bn groups. Selective and orthogonal deprotection of N-Boc, N-Cbz, N-Fmoc and O-Bn groups could be achieved in the presence of the N-Bus protecting group. The new unnatural amino acids (3R, 2R) 3–methyl-D-leucine (β-Me-Leu) and its 2-methyl regioisomer were synthesized by ring opening of an N-Ts aziridine intermediate with excess LiMe2Cu. The 1:1.2 mixture of regioisomers were each converted to the corresponding methyl leucines, then coupled to D-phenyllactic acid, followed by coupling with 2-carboxyperhydroindole 4-amidino-benzamide core in the presence of DEPBT. Further elaboration led to linear peptidic unnatural analogues of known aeruginosins such as chlorodysinosin A. The two analogues were also evaluated in enzymatic assays for their inhibitory activity against thrombin and trypsin. The presumed 3-sulfated aeruginosin 205B and its β–anomer were successfully synthesized from 5 subunits: 3-chloroleucine, D-phenyllactic acid, D-xylose, 2-carboxy-6-hydroxyoctahydroindole, and agmatine. Comparison of 1H and 13C NMR reported data with that of synthetic aeruginosin 205B revealed a disturbing discrepancy with regard to the position of the presumed 3'-sulfate on the D-xylopyranosyl unit. We synthesized methyl α-D-xylopyranosides with sulfates at each of the hydroxyl groups and conclusively demonstrated the the presence of a C-4'-sulfate by comparison of the 1H and 13C NMR spectroscopic data. Thus, the structure of aeruginosin 205B should be revised. One of the key steps in the synthesis is glycoside formation of the axially oriented C-6 hydroxyl group in the Choi subunit. The 2-thiopyridyl carbonate was a suitable method for anomeric activation, followed by treatment with AgOTf and tetramethylurea in ether-DCM solution to give the desired α-anomer, which was easily separable from the β-anomer by column chromatography.

A atividade catalítica de clusters trigonais de acetato de rutênio e porfirinas supramoleculares contendo quatro unidades de clusters periféricos ou complexos de bis(bipiridina)rutênio, na oxidação de substratos orgânicos por iodosil-benzeno ou terc-butil-hidroperóxido, é abordada nesta tese. Foram feitos estudos cinéticos para elucidar o mecanismo de catálise, com especial destaque para duas espécies supramoleculares isoméricas representadas por Mn(3-TRPyP) ou Mn(4-TRPyP), nos quais os complexos de bis(bipiridina)(cloro)rutênio se coordenam à tetrapiridilporfirina através das posições meta ou para da ponte piridínica, respectivamente. Além da maior seletividade proporcionada pelos catalisadores supramoleculares, a substituição do íon cloreto pela água nos complexos periféricos de rutênio, intensificou a atividade catalítica, gerando novos sítios ativos, do tipo Ru(IV)=O. Também foram estudados clusters trinucleares de rutênio, altamente reativos, no estado Ru(III)Ru(IV)Ru(IV)=O. Estes foram gerados eletroquimicamente em solução aquosa, apresentando pronunciada atividade catalítica na oxidação do alcool benzílico. Finalmente, uma espécie dimérica de cluster, ainda inédita, com ponte oxo, foi caracterizada e investigada do ponto de vista catalítico. / The catalytic activity of trinuclear ruthenium clusters and supramolecular tetrapyridylporphyrins containing four peripheral cluster units or bis(bipyridine)ruthenium complexes, in the oxidation of organic substrates by iodosylbenzene or tert-butil-hydroperoxide, is dealt with in this thesis. Kinetic studies were performed in order to elucidate the mechanisms of catalysis involving two isomeric species denoted Mn(3-TRPyP) or Mn(4-TRPyP), in which the bis(bipyridine)(chloro)ruthenium complexes are bound to the tetrapyridylporphyrin center, at the meta or para positions of the pyridine bridge, respectively. In addition to the improved selectivity by such supramolecular catalysts, the substitution of the chloride ion by water in the peripheral ruthenium complexes, greatly enhanced their catalytic activity by generating new Ru(IV)=O reactive sites. Highly reactive trinuclear ruthenium clusters of the type Ru(III)Ru(IV)Ru(IV)=O were also generated electrochemically in aqueous solution, exhibiting pronounced catalytic activity in the oxidation of benzyl alcohol. Finally, a novel dimeric oxo-bridged cluster species was characterized, and its role in catalysis investigated.

Dye sensitized solar cells (DSSCs) have typically been produced using organic liquids such as acetonitrile as the electrolyte solvent. In real world situations water can permeate into the cell through sealing materials and is also likely to be introduced during the fabrication process. This is a problem as the introduction of water into cells optimized to use an organic solvent tends to be detrimental to cell performance. In this work DSSCs which are optimized to use water as the main electrolyte solvent are produced and characterized. Optimization of aqueous DSSCs resulted in cells with efficiencies up to 3.5% being produced. In terms of characterization, it is generally seen in this work that aqueous DSSCs produce a lower photocurrent but similar photovoltage compared to DSSCs made using acetonitrile and reasons for this are examined in detail. The decreased ability of the aqueous electrolyte to wet the nanoporous TiO2 compared to an acetonitrile electrolyte is found to be a key difficulty and several possible solutions to this problem are examined. By measuring the photocurrent output of aqueous cells as a function of xy position it can be seen that there is some dye dissolution near to the electrolyte filling holes. This is thought to be linked to pH and the effect of 4-tert-butylpyridine and may also decrease the photocurrent. It is found that there is little difference between the two types of cells in terms of the conduction band position and the reaction of electrons in the semiconductor with triiodide in the electrolyte, explaining the similarity in photovoltage. By altering the pH of the electrolyte in an aqueous cell it is found to be possible to change the TiO2 conduction band position in the DSSC. This has a significant effect on the open circuit voltage and short circuit current of the cell, though the pH range available is limited by the fact that dye desorbs at high pH values.