Orientadores: Marcos Cesar de Oliveira, Silvio Antonio Sachetto Vitiello / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-22T14:05:32Z (GMT). No. of bitstreams: 1 CarrilloLozada_Alejandro_M.pdf: 43030851 bytes, checksum: 63a4000c6fbaa12db70efa1fc8fa2a1b (MD5) Previous issue date: 2013 / Resumo: O campo magnético da Terra é essencial na orientação de pássaros migratórios. A explicação mais promissora para esta orientação utiliza o mecanismo de pares ra-dicais (PR) criados em uma reação foto-estimulada, a qual é conjecturada ocorrer em fotorreceptores criptocromo. Esta última conjectura foi particularmente reforçada recentemente pela evidência de sensibilidade magnética do criptocromo humano. Os radicais devem ter uma anisotropia intrínseca, a fim de definir um quadro de referência para esse tipo de bússola. Esta anisotropia, quando introduzida através de interação hiperfinas, impõe imobilidade ao RP formado dentro do olho do pássaro, e implica na preservação do emaranhamento entre os elétrons desemparelhados do PR por tempos longos (de centenas de microssegundos). Consequentemente, os tempos de coerência são também longos, mesmo que o papel do emaranhamento na reação permaneça desconhecido. Mostra-se que esse tipo de anisotropia devido às interações hiperfinas não é necessário para o funcionamento da bússola. Pares radicais isotrópicos, isto é, moléculas que executam um movimento de rotação ou de difusão capaz de remover qualquer anisotropia no Hamiltoniano quando submetidos a um processo de decoerência rápida, são capazes de fornecer a anisotropia necessária para que a bússola funcione. O ambiente no qual o PR está imerso _e responsável pelo referencial da bússola, relaxando a hipótese de imobilidade. Isto expande significativamente a gama de aplicabilidade do mecanismo de PR fornecendo mais elementos para pesquisa experimental, quanto as moléculas candidatas não devem estar fixas na retina. Utilizando esta fonte externa de anisotropia, mostramos que o emara-nhamento não é necessário para o bom funcionamento da bússola dado que estados separáveis podem formar produtos anisotrópicos sob as condições apropriadas. Condições iniciais classicamente correlacionadas para o PR, ou em outras palavras, estados iniciais sem correlação quântica, podem fornecer uma outra fonte da anisotropia necessária para o bom funcionamento da bússola; dado que o estado inicial não _e um estado singleto (ou tripleto) perfeito entre os spins eletrônicos e portanto não _e um estado maximamente emaranhado, esta nova fonte de direção preferencial na criação dos produtos químicos ganha relevância / Abstract: Earth's magnetic field is essential for orientation of migratory birds. The most promising explanation for this orientation employs the photo-stimulated radical pair (RP) mechanism, conjectured to occur in cryptochrome photoreceptors. This last conjecture has been particularly reinforced recently by the evidence of magnetosensivity of human cryptochrome. The radicals must have an intrinsic anisotropy in order to define a reference frame for this kind of compass. This anisotropy, when introduced through hyperfine interactions, imposes immobility of the RP formed within the eye of the bird, and implies that entanglement between the unpaired electrons of the RP is preserved over long times of hundreds of microseconds; therefore the coherence times are longer, even if the role of entanglement in the reaction remains unknown. We show that this kind of anisotropy due to hyperfine interactions is not necessary for the proper functioning of the compass. Isotropic radical pairs, i.e., molecules performing diffusional or rotational motion able to average away any anisotropy in the hamiltonian, when subjected to a fast decoherence process, are able to provide the anisotropy required for the compass to work. The environment in which the RP is immersed is then responsible for the reference frame of the compass, relaxing the immobility assumption. This significantly expands the range of applicability of the RP mechanism providing more elements for experimental search, as the candidate molecules must not be fixed within the retina. Using this external source of anisotropy, we show that entanglement is not necessary for the proper working of the compass, given that separable states can form anisotropic yields under proper conditions. Classically correlated initial conditions for the RP, or in other words, initial states without quantum correlations, can provide another source of the required anisotropy for the proper working of the compass; given that the initial state is not a perfect singlet (or triplet) state between the electronic spins and therefore is not a maximally entangled state, this new source of preferred direction in the creation of the chemical products gains relevance / Mestrado / Física / Mestre em Física

Made available in DSpace on 2014-08-20T13:46:40Z (GMT). No. of bitstreams: 1 Zaira Maria Arretche_Dissertacao.pdf: 767049 bytes, checksum: 415dbfa6b2a80e7434eec25f1e1859dc (MD5) Previous issue date: 2011-03-11 / This essay examines the concepts of political representation of three contemporary democratic theories. It aims at exploring their theoretical consistency both regarding the democratic process and the electoral representativeness. The elitist theory of democracy, as framed by Joseph Schumpeter, is based upon the assumption that voters lack discernment skills while political elites have leadership capacity. As a result, representation can be grounded on authority formalism, as well as political participation could be restricted to the choice of representatives. Democracy would be ensured by this decision-making method. The republicanist Philip Pettit's theory, by its turn, is based on republican principles. The non-domination ideal requires the active participation of society, not only in the choice of representatives. Instead, the capability to compete in the decision sphere of power would allow voters to recall representatives by means of control mechanisms established by the rule of law. The theory of radical democracy, as framed by Ernesto Laclau and Chantal Mouffe, lacks the prescriptive features of the two previous ones. It is based on a new analytical perspective of society, which breaks with essentialism dichotomy. They propose an agonistic model of democracy, which takes into account the plural nature of manhood, which is antagonistic and affectionate. As a result, this theory frames the role of representatives differently. As theories of representative democracy, these models of representation present themselves as critical operacionalization, with internal contradictions. As a result, they may, on some dimensions, de-constitute themselves either as democratic theories or as theories of representation. / Esta dissertação analisa as ideias de representação política de três teorias contemporâneas da democracia, com o propósito de demonstrar sua pertinência teórica no que diz respeito ao processo democrático e à representatividade eleitoral. A ideia de representação na teoria democrática elitista, tal como postulada por Joseph Schumpeter, baseia-se no pressuposto da incapacidade de discernimento por parte do eleitor, em contraposição à capacidade de liderança da elite política. Este pressuposto empírico conferiria justificativa moral para o formalismo da autoridade e à participação eleitoral restrita à escolha dos representantes. Nestas bases, as decisões políticas seriam democráticas. A teoria republicana, por sua vez, tal como formulada por Philip Pettit, tem por base o ideal de não-dominação. Por ser republicana, requer a participação ativa da sociedade, para além da escolha dos representantes. O cidadão teria capacidade para disputar decisões nas esferas de poder e destituir seus representantes, através da instituição do império da lei, com diversos mecanismos de controle. Por fim, a teoria da democracia radical, tal como formulada por Ernesto Laclau e Chantal Mouffe, não apresenta as características prescritivas das teorias anteriores. Baseia sua análise da sociedade em uma nova perspectiva, de ruptura com o essencialismo dicotômico. Propõe um modelo agonístico da democracia, que leva em consideração a natureza humana plural, antagônica e afetiva. Estes pressupostos implicam um reordenamento da função dos representantes. Enquanto teorias da democracia representativa, estes modelos de representação constituem-se em uma operacionalidade fundamental, os quais podem apresentar, algumas vezes, contradições internas, culminando por desconstituí-las como teorias democráticas ou como teorias representativas.

Ribonucleotide reductases (RNR) are essential enzymes that catalyze the reduction of ribonucleotides to 2'-deoxyribonucleotides, which is a critical step that produces precursors for DNA replication and repair. The inactivation of RNR, logically, would discontinue producing the precursors of the DNA of viral or cancer cells, which then would consequently end the cycle of DNA replication. Among different compounds that were found to be inhibitors of RNR, 2'-azido-2'-deoxynucleotide diphosphates (N3NDPs) have been investigated in depth as potent inhibitors of RNR. Decades of investigation has suggested that the inactivation of RNR by N3NDPs is a result of the formation of a nitrogen-centered radical (N•) that is covalently attached to the nucleotide at C3' and cysteine molecule C225 [3'-C(R-S-N•-C-OH)]. Biomimetic simulation reactions for the generation of the nitrogen-centered radicals similar to the one observed during the inactivation of the RNR by azionuclotides was investigated. The study included several modes: (i) theoretical calculation that showed the feasibility of the ring closure reaction between thiyl radicals and azido group; (ii) synthesis of the model azido nucleosides with a linker attached to C3' or C5' having a thiol or vicinal dithiol functionality; (iii) generation of the thiyl radical under both physiological and radiolysis conditions whose role is important in the initiation on RNR cascades; and (iv) analysis of the nitrogen-centered radical species formed during interaction between the thiyl radical and azido group by electron paramagnetic resonance spectroscopy (EPR). Characterization of the aminyl radical species formed during one electron attachment to the azido group of 2'-azido-2'-deoxyuridine and its stereospecifically labelled 1'-, 2'-, 3'-, 4'- or 5,6-[2H2]-analogues was also examined. This dissertation gave insight toward understanding the mechanism of the formation of the nitrogen-centered radical during the inactivation of RNRs by azidonucleotides as well as the mechanism of action of RNRs that might provide key information necessary for the development of the next generation of antiviral and anticancer drugs.

Os mecanismos oxidativos pelos quais macrófagos exercem atividade microbicida permanecem em discussão, e estudos com hospedeiros animais serão essenciais para elucidar tal questão. Nesse trabalho, estudamos os mecanismos microbicidas de macrófagos in vivo comparando parâmetros de infecção nas lesões de camundongos resistentes (C57Bl/6) e suscetíveis (BALB/c) ao protozoário Leishmania amazonensis. A comparação mostrou que o controle da infecção pelos camundongos resistentes é dependente da ativação de macrófagos com expressão da enzima óxido nítrico sintase induzível, síntese de óxido nítrico e extensa nitração e hidroxilação das proteínas dos parasitas dentro dos fagolisossomos dos macrófagos. O principal agente tóxico aos parasitas parece ser derivado do peroxinitrito porque a nitração dos parasitas ocorreu na ausência virtual de células polimorfonucleares e foi acompanhada de hidroxilação. Além disso, tempol um inibidor de reações de nitração mediadas por peroxinitrito, inibiu a nitração de proteínas da lesão e aumentou o número de parasitas nelas presentes. Também, estudos com parasitas em cultura confirmaram que o peroxinitrito é citotóxico aos parasitas enquanto o óxido nítrico é citostático. O camundongo suscetível se mostrou capaz de sintetizar óxido nítrico mas o fez em estágios tardios da infecção e, provavelmente, em resposta a uma infecção secundária por bactérias. Tomados conjuntamente, os resultados indicam que o peroxinitrito e radicais dele derivados são os principais agentes leishmanicidas produzidos por macrófagos in vivo. / Macrophage oxidative microbicidal mechanisms remain debatable and their elucidation is likely to depend on studies with mammalian hosts. To examine macrophage microbicidal mechanisms in vivo, we compared infection parameters in the lesions of resistant (C57Bl/6) and susceptible (BALB/c) mice to the protozoan Leishmania amazonensis. This comparison demonstrated that infection control by resistant mice relied on macrophage activation with inducible nitric oxide synthase expression, nitric oxide synthesis and extensive nitration and hydroxylation of the proteins of the parasites inside macrophage phagolysosomes. The toxic agent to the parasite is likely to be peroxynitrite-derived because parasite nitration occurred in the virtual absence of polymorphonuclear cells and was accompanied by parasite hydroxylation. In addition, tempol, an inhibitor of peroxynitrite-mediated nitrations, inhibited protein nitration of the lesions and increased the number of parasites in them. Also, studies with parasite cultures confmed that peroxynitrite is cytotoxic to the parasites whereas nitric oxide is cytostatic. The susceptible mice were also able to synthesize nitric oxide but only at late infection time and, most likely, in response to a secondary bacterial infection. Taken together, the results indicate that peroxynitrite and derived radicals are the main leishrnanicidal agents produced by macrophages in vivo.

N,N,N\',N \'-tetrametil-p-fenilenodiamina (TMPD) catalisa a autoxidação de coenzimas piridínicos (NADH, NADPH) e modelos (ClBCH ,ClPCH ) ao cátion piridínico com rendimentos de 80-100%. A velocidade destas reações mostrou dependência de primeira ordem com respeito à concentração da 1,4-dihidronicotinamida e de meia ordem em relação às concentrações de O2 e TMPD. Estes dados cinéticos e testes com captadores de ion superóxido e superóxido dismutase indicam que os radicais HO•2 oriundos da autoxidação lenta do TMPD promovem a oxidação da dihidronicotinamida numa reação em cadeia; no término os radicais HO•2 se aniquilam por dismutação. O mecanismo proposto também é confirmado (1º) pela razão kC-H/kC-D=2,3 quando se substitui um dos hidrogênios do C4 de ClBCH por deutério, (2º) pelas idênticas velocidades iniciais em H2O e D2O, (3º) pelo valor da Ea = 10 kcal/mol na autoxidação do NADH e (4º) pelo aumento da velocidade de pH = 7,8 a pH 6,5. TMPD também promove a autoxidação do derivado 5, 6-hidratado (PHTN) da dihidronicotinamida ao cátion piridínico (ClPC+) apenas de fosfato ou arsenato estão presentes. O ClPC+ nã o se forma a partir do ClPCH em equilíbrio com o PHTN. Muito provavelmente se forma a partir do intermediário fosforilado no C6 por oxidação no C4 seguida de eliminação de fosfato. Quando PHTN e ClPCH foram oxidados pelo sistema O2/TMPD na presença de fosfato de piridínio ou de tetra-n-butilamônio em meio piridínico houve formação de pirofosfato, isolado por cromatografia de papel e por resina de troca aniônica. Adicionando-se ADP de tetra-n-butilamôneo ao sistema, constatou-se a formação de pirofosfato e de ATP com rendimentos mínimos de 5% e 3% , respectivamente. Por outro lado se a mistura de reação contém AMP de tetra-n-butilamôneo pôde-se verificar a formação de pirofosfato, ADP e ATP com rendimento total de 28% de \"ligações ricas\". A reação estudada foi proposta como modelo para síntese de ATP no sítio I da cadeia respiratória. / N,N,N\',N\'-tetramethyl-p-phenylenediamine (TMPD) catalyses the autoxidation of the pyridine coenzymes and of their models to the pyridinium form (80-100% yields). The first arder dependence of the rate upon the dihidronicotinamide concentration and half order upon both the O2 and TMPD concentrations, indicates that the relatively slow autoxidation of TMPD is the source of free radicals: dihydronicotinamide autoxidizes by the HO•2 chain mechanism and in the termination step the HO•2 radicals decay by dismutation. Such a mechanis is also supported by the inhibitory effects of cathecol, a scavenger of the HO•2 radical, and of superoxide dismutase, an enzyme which accelerates the dismutation of the O-2/ HO•2 species. The mecanism is further supported by (1) kC-H/kC-D=2,3 for substitution in 1-benzyl-1,4-dihydronicotinamide (ClBCH), (2) identical rates in H2O and D2O buffers, (3) Ea = 10 kcal/mole in the autoxidation of NADH and (4) the increase in rate from pH 7,8 to 6,5. TMPD promotes also the autoxidation of 1-n-propyl-6-hydroxy-1,4,5,6 - tetrahydronicotinamide (PHTN) to the 1-propyl-3-carboxamidopyridinium cation (ClPC+) provided phosphate ar arsenate are present. ClPC+ originates not from 1-n-propyl-1,4-dihydronicotinamide (ClPCH) in equilibrium with PHTN but most certainly from a C6 phosphorylated intermediate by oxidation at C4 and loss of phosphate. When PHTN an ClPCH were oxidated by the system O2/TMPD in the presence of pyridinium phosphate or tetra-n-butylammonium phosphate in pyridineas solvent, formation of pyrophosphate occurred. Pyrophosphate was isolated and identified by paper and ionic exchange resin chromatography. If tetra-n-butylammonium ADP is also present in the system, one can observe the formation of both pyrophosphate and ATP (5% and 3% minimum yields, respectively). In the presence of tetra-n-butylammonium AMP there, formation of pyrofosphate, ADP and ATP occurs. The total yield of energy rich bond is 28%. We suggest that the reaction is a model for the generation of the first ATP in the respiratory chain.

Des mesures de radiolyse impulsionnelle avec des paquets d’électron de 7 picosecondes ont été effectuées dans des systèmes D₂O et D₂SO₄ / D₂O purs afin d'étudier l'effet isotopique sur la réactivité de l'électron solvaté (es⁻), du radical hydroxyle (OH•) et de son radical cation cationique (H₂O•⁺). Dans le système D₂O, le spectre d'absorption molaire de l’électron solvaté dans D₂O a été déterminé entre 250 et 1500 nm en utilisant la méthode du point isosbestique. Sur la base de ce coefficient d'extinction, le rendement radiolytique de es⁻ dans D₂O juste après l'impulsion d'électrons de 7 ps a été déterminé à (4,4 ± 0,2) × 10⁻⁷ mol J⁻¹, ce qui coïncide avec celui dans H₂O. Le rendement du radical OD• juste après l'impulsion d'électrons s'est révélée être (5,0 ± 0,2) × 10⁻⁷ mol J⁻¹. Dans le cas de l’électron solvaté la vitesse de déclin dans D₂O est plus lent que dans H₂O, tandis que la vitesse de déclin de OD• est similaire à celui de OH•. Dans le système D₂SO₄ /D₂O, la réactivité de D₂O•⁺ a été sondée dans des solutions d'acide sulfurique deutérées de diverses concentrations et comparée à celle de H₂O•⁺. Le soluté oxydé, le radical sulfate a été observé à 7 ps et des rendements plus élevés ont été trouvés dans les solutions deutérées. Les effets isotopiques révèlent la compétition entre deux réactions ultra-rapides : le transfert de protons vers H₂O (D₂O) et le transfert d'électrons de H₂O•⁺ (D₂O•⁺). Les simulations par la théorie de la densité fonctionnelle décryptent le mécanisme du transfert d’électrons : elles se font par migration de charge sub-femtoseconde et ne sont pas affectées par la substitution isotopique. / Picosecond pulse radiolysis measurements were performed in neat D₂O and D₂SO₄/D₂O system in order to study the isotopic effect on the reactivity of the solvated electron(es⁻), the hydroxyl radical (OH•) and its precursor—water cation radical (H₂O•⁺). In D₂O system, the molar absorption coefficient spectra of spectrum in D₂O was determined between 250 to 1500 nm using the isosbestic point method. Based on this extinction coefficient, the radiolytic yield of es⁻ in D₂O just after the 7 ps electron pulse was determined to be (4.4 ± 0.2) × 10⁻⁷ mol J⁻¹, which coincides with the one for in H₂O. The yield of the radical OD• just after the 7 ps electron pulse was found to be (5.0 ± 0.2) × 10⁻⁷ mol J⁻¹. In the spurs of ionization, the decay rate of es⁻ is slower in D₂O than that in H₂O, whereas the decay rate of OD• is similar to the one of OH•. In D₂SO₄/D₂O system, the reactivity of and D₂O•⁺ was probed in deuterated sulfuric acid solutions of various concentrations and compared with that of H2O•⁺. The oxidized solute sulfate radical was observed at 7 ps and remarkably higher yields are found in deuterated solutions. The isotopic effects reveal the competition between two ultrafast reactions: proton transfer toward H₂O (D₂O) and electron transfer from H₂SO4⁻ to H₂O•⁺ (D₂O•⁺). Density functional theory simulations decipher the electron transfer mechanism: it proceeds via sub-femtosecond charge migration and is not affected by isotopic substitution.

Le microbiote humain est constitué de milliers d’espèces bactériennes qui synthétisent de nombreux métabolites secondaires. Cependant, notre connaissance des produits naturels dérivés du microbiome est encore limitée. Parmi eux, les RiPPs (Ribosomally Synthesized and Post-translationally modified Peptides) apparaissent comme une famille majeure de produits naturels possédant diverses structures et fonctions biologiques dont des propriétés antibiotiques, en faisant une famille de molécules d’intérêt majeur pour la santé publique. La biosynthèse des RiPPs commence par la traduction d’un peptide précurseur, qui est ensuite maturé par l’action d’une ou plusieurs enzymes avant l’excision d’une séquence signal et l’export du produit naturel actif. La diversité structurale et fonctionnelle des RiPPs démontre la nécessité de la compréhension des voies de biosynthèse de ces produits naturels, de l’étude systématique des mécanismes de modification et de la caractérisation des maturases associées. En particulier, une famille de métallo-enzymes, les enzymes à radical S-adénosyl-L-méthionine (SAM), a récemment été impliquée dans la biosynthèse de nombreux RiPPs. Ces enzymes catalysent un large éventail de réaction, via un mécanisme de chimie radicalaire, aboutissant à une grande variété de modifications post-traductionnelles. Néanmoins, les voies de biosynthèse de nombreux RiPP restent mal comprises.En 2011, il a été montré que Ruminococcus gnavus, un membre important du microbiote humain, produisait un peptide actif contre Clostridium perfringens, la Ruminococcin C (RumC). Le séquençage de l’opéron de biosynthèse de RumC montre la présence de cinq gènes codants des peptides précurseurs (RumC1-5) et deux gènes codant des enzymes (RumMC1 et RumMC2).L’objectif de ma thèse est de mieux comprendre les voies de biosynthèse des produits naturels au sein du microbiome humain. Nous avons démontré l’appartenance des protéines RumMC1 et RumMC2 à la famille des enzymes à radical SAM, ainsi que leurs implications dans la formation de quatre modifications post-traductionnelles (ponts α-thioether) essentielles à l’activité antibiotique de RumC1 et RumC2. Ces études nous ont permis de proposer un mécanisme catalytique pour la maturation de la Rummonicoccin C et ainsi de mieux documenter cette famille d’enzymes émergentes. / The human microbiota consists of thousands bacterial species which synthesize numerous secondary metabolites. However, our knowledge of microbiome-derived natural products is still limited. Among them, RiPPs (Ribosomally synthesized and Post-translationally modified Peptides) are emerging as a major family of natural products possessing diverse structures and biological functions including antibiotic properties, making them a major family of molecules of interest for public health. The biosynthesis of RiPPs occurred by the translation of a precursor peptide, which is then matured via the action of one or more enzymes before the excision of a signal sequence and the export of the active natural product. The structural and functional diversity of RiPPs demonstrates the need for understanding the biosynthetic pathways of these natural products, the systematic study of the modification mechanisms and the characterization of associated maturases. In particular, a family of metallo-enzymes, the S-adenosyl-L-methionine radical (SAM) enzymes, has recently been implicated in the biosynthesis of many RiPPs. These enzymes catalyze a wide range of reactions, via a mechanism of radical chemistry, resulting in a wide variety of post-translational modifications. Nevertheless, the biosynthetic pathways of many RiPPs remain poorly understood.In 2011, it was shown that Ruminococcus gnavus, a major member of the human microbiota, produced an active peptide against Clostridium perfringens, Ruminococcin C (RumC). Sequencing of the RumC biosynthesis operon shows the presence of five genes encoding precursor peptides (RumC1-5) and two genes encoding enzymes (RumMC1 and RumMC2).The aim of my thesis is to understand the biosynthetic pathways of natural products within the human microbiome. We have demonstrated that the RumMC1 and RumMC2 proteins belong to the radial SAM enzyme family, as well as their involvement in the formation of four post-translational modifications (α-thiother bridges) essential for the antibiotic activity of RumC1 and RumC2. These studies allowed us to propose a catalytic mechanism for the maturation of Rummonicoccin and thus to better document this family of emerging enzymes.

No description available.

Project I Celogentin C, isolated by Kobayashi from the seeds of Celosia argentea in 2001 exhibits strong inhibitory behavior towards polymerization of tubulin – globular protein, which plays crucial role during the cell division cycle. We have attempted synthesis of the left-hand ring of celogentin C via the intramolecular alkylation and the Knoevenagel condensation strategies. Utilizing synthetic methodologies in the field of nitroacetyl chemistry, developed by Kornblum and Rajappa we have successfully prepared the intermolecular Knoevenagel condensation product – the late-stage precursor to the left-hand ring of celogentin C. Synthesis of this key intermediate subsequently led to the preparation of the left-hand ring and the total synthesis of celogentin C by other members of Castle's group. Project II Thioviridamide is the potent apoptosis inducer isolated by Hayakawa from the bacterial broth of Streptomyces olivoviridis. Unusual structural features of the thioviridamide macrocycle contain two novel amino acids, never before encountered in a natural product - S-(2-aminovinyl)cysteine (avCys) and β-hydroxy-N1,N3-dimethylhistidinium (hdmHis). No stereochemical information except for the Z-configuration of the β-thioenamide linkage was reported in the literature. We have performed a computational study to predict the thioviridamide stereochemistry. Initial populations of conformers for the likely candidate structures were produced using OPLS-AA force field. Prediction of the NMR properties was accomplished at the mPW1PW91/6-311+G(2d,p) level of theory with the polarizable continuum model of salvation. Utilizing Boltzmann averaging and statistical analysis we have determined that the only possible cases of stereochemical inversion occur at the sites of the two novel amino acids. Project III Model studies towards the synthesis of the β-thioenamide subunit of thioviridamide were performed. The radical addition reaction of thiyl radicals to ynamides produces Z- (kinetic products) or E- β-thioenamides (thermodynamic products) depending on the reaction conditions. Two distinct sets of reaction conditions allowing kinetic or thermodynamic control of β-thioenamide formation were developed. Synthesis of the model β-thioenamide subunit of thioviridamide was attempted.

[pt] A modernidade representou um novo período de mudanças para o mundo, com o desenvolvimento da indústria, das máquinas e das tecnologias, além da metropolização das grandes cidades, que alterou a percepção e os quadros de vida do citadino. Com as mudanças empreendidas durante este período, foi possível notar um novo interesse pelo cotidiano urbano. Os acontecimentos históricos, assim como a revolução estética na Arte e o fim das utopias levam a crer que o olhar crítico para o cotidiano é uma das maneiras de indagar o pensamento contemporâneo. A partir de exemplos de travessias deste cotidiano na arte, como a exposição Cotidiano radical, de Marco Paulo Rolla (2015) e o filme Relatos Selvagens, de Damián Szifron (2014), esta dissertação pretende elucidar de que maneira a arte consegue mobilizar não só o cotidiano banal, mas também o cotidiano radical, definindo esta radicalidade, que potencializa o efeito reflexivo do contemporâneo. / [en] The modernity represented a new period of changings to the world, with the development of Industry, the machines and the technologies, besides the metropolization of the great cities, that changed the perception and the scenes of the urban life of citizen. With the changing during this period, as the aesthetic revolution in Art, and the end of the utopias, makes us wonder that the critic view to the everyday life is one of the many ways to inquire the contemporary thinking. From the examples of crossings of this everyday life in art, like the exhibition Radical everyday life, from Marco Paulo Rolla (2015), and the film Wild tales, from Damián Szifron (2014), this dissertation intend to elucidate in which way art can mobilize not just the banal everyday life, but also the radical everyday life, defining this radicality, that potencializes the reflexive effect in the contemporary.