A produção de radicais de carbono \"in vivo\" durante a biotransformação da hidrazina foi demonstrada por ressonância para magnética eletrônica, utilizando o método do captador de spin. Eritrócitos de rato também oxidaram a hidrazina, formando radicais de carbono e nitrogênio, além de espécies reativas de oxigênio. Todas estas espécies, possivelmente formadas \"in vivo\", são potencialmente causadoras de dano a macromoléculas. Podem, por exemplo, iniciar reações secundárias formando radicais de componentes celulares, como ocorreu com a hemoglobina que foi oxidada a radicais tiil-hemoglobina em eritrócitos tratados com hídrazina. Radicais de carbono formados durante a biotransformação da hidrazina em animais expostos provêm necessariamente de substâncias endógenas e podem ser direta ou indiretamente responsáveis pela modificação ( alquilação ) de bases no DNA \"in vivo\". A hidrazona do formaldeído é descrita na literatura como um intermediário da alquilação induzida por hidrazina \"in vivo\". Células L 1210, catalase ou oxihemoglobina de rato foram capazes de formar radicais de carbono durante a oxidação da hidrazona do formaldeído. A oxidação da hidrazona do formaldeído pela catalase foi estudada \"in vítro\" e os radicais de carbono formados, identificados como radicais metila. A base modificada C8 -metil-guanina foi formada em animais expostos, como demonstrado por cromatografia líquida de alta eficiência associada à detecção eletroquímica, sugerindo que ocorreu alquilação do DNA por radicais metila durante a biotransformação da hidrazina \"in vivo\". / The production of carbon-centered radicais during hydrazine biotransformation \"in vivo\" was demonstrated by electron paramagnetic resonance ( EPR ) spin trapping technique. Rat red blood cells also oxidized hydrazine, forming carbon and nitrogen centered radicais, besides oxygen reactive speties. Ali these species, possibly formed \"in vivo\", are potentially harmful to macromolecules. For example, they can initiate secondary reactions in which the radicais from cell components are formed, as it occurred with hemoglobin, forming thiyl-hemoglobin radicais in the red blood cells treated with hydrazine. Carbon-centered radicais produced during the biotransformation of hydrazine in exposed animais must be derived from endogenous sources and may be directly or indirectly responsible for the modificaton ( alkylation ) of DNA bases \"in vivo\". The formaldehyde hydrazone is reported in the literature as an intermediate of hydrazine-induced alkylation \"in vivo\". L1210 cells, catalase and rat hemoglobin were able to produce carbon-centered radicais during the oxidation of the formaldehyde hydrazone. The oxidation of formaldehyde hydrazone by catalase was studied \"in vitro\" and the generated carbon-centered radicais were identified as methyl radicais. The modified base C8 -methylguanine was formed in exposed animais, as demonstrated by high performance liquid chromatography with electrochemical detection, suggesting that DNA alkylation by methyl radicais occurred during hydrazine biotransformation \"in vivo.\"

The focus of this research was to improve the sustainability of various processes by employing tunable solvents, switchable solvents, and catalysis. In Chapter 2, we report applications of tunable solvents to metal and enzyme catalyzed reactions of hydrophobic substrates. Tunable solvents are defined as solvent that change properties rapidly but continuously upon the application of an external physical stimulus and we utilize these solvents to couple homogeneous reactions with heterogeneous separations. We developed organic-aqueous tunable solvents that utilize propane for efficient phase separation at moderate pressures around 1 MPa; for example the water contents in the propane-expanded THF is 3 wt% at 0.8MPa at 30°C. Also, we extended the use of CO2-organic-aqueous tunable solvents to a pharmaceutically-relevant reaction--the hydroformylation of p-methylstyrene. The homogeneous reactions provide fast rates with excellent yields. At 60°C, the reaction reaches completion after 180 minutes with 95% branched aldehyde yield. The CO2-induced heterogeneous separation of the product from the catalyst provides an efficient and simple way to remove 99% of the product, to retain 99.9% of catalyst, and to recycle the Rh-TPPMS catalyst for five consecutive reactions. In chapter 3, we investigated the use of reversible ionic liquids (RevILs) for synthesis of nanoparticles. RevILs are formed by the reversible reaction of compounds with basic nitrogen functionalities (molecular liquid) with CO2 at ambient pressure to form a liquid salt (ionic liquid). We demonstrated that RevILs form microemulsions that can be switched-on by bubbling CO2 and switched-off by heating. These microemulsions solubilize ionic compounds such as chloroauric acid. We utilized these microemulsions as a template for controlled synthesis of gold nanoparticles. With 2-component RevILs, [TMBGH]+[O2COCH3]-/N-propyl-octylsulfonamide/hexane were used to form particles in the size range of 6-20 nm with an average particles size of 11.4±3.3. With 1-component RevILs, (3-aminopropyl)-tripropylsilane was used to prepare semi-spherical gold particles with an average size of about 20nm. The 1-component RevILs systems provide a simpler method to form microemulsions when compared to the 2-componenet RevILs systems since they eliminate the need for alcohols and surfactants. In chapter 4, we developed a catalyst that efficiently decomposes hydrazine to selectively produce ammonia. This enables the use of the chemical propulsion hydrazine for electric propulsion as well. We prepared nickel, copper, cobalt, ruthenium, rhodium, and iridium nanoparticles that were supported on silica and we tested these silica-supported metals for the decomposition of hydrazine. To study the catalytic activity, we designed and constructed a continuous flow reactor. The results show that nano-nickel supported on silica is the most active and selective catalyst with 100% conversion of hydrazine and 94±3% yield of ammonia.

Made available in DSpace on 2014-06-11T19:25:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-26Bitstream added on 2014-06-13T19:12:22Z : No. of bitstreams: 1 sa_ac_me_ilha.pdf: 1061286 bytes, checksum: b370fdf160f4689709efe584af803c2a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste trabalho esta resumido através de três etapas. 1 - A primeira etapa consistiu em funcionalizar e caracterizar a sílica gel com grupos 3- aminopropiltrietoxisilano. Nesta etapa o material obtido (Si) foi caracterizado por técnicas de Ressonância Magnética Nuclear no estado sólido (24Si e 13C) e espectroscopia vibracional (FTIR). 2- Numa segunda etapa promoveu-se a adsorção de íons de cobre (II) e de cobalto (II) na superfície da sílica (Si). Os materiais obtidos (SiCu e SiCo) foram caracterizados por espectroscopia vibracional e voltametria cíclica. 3- Na terceira etapa reagiu-se os materiais preparados (SiCu e SiCo) com nitroprussiato de sódio para formar os complexos binucleares (SiCuNP e SiCoNP). Estes materiais também foram caracterizados por espectroscopia vibracional e voltametria cíclica. Estes materiais foram utilizados na construção do eletrodo de pasta de grafite e testados na oxidação eletrocatalítica de substâncias biologicamente importantes tais como a hidrazina e N-acetilcisteína sendo empregado para isto a técnica de voltametria cíclica. Observou-se que o eletrodo de SiCuNP apresentam dois pares redox nos potenciais (Em)1 = 0,34 V e (Em)2 = 0,76 V vs Ag/AgCl, O primeiro foi atribuído ao processo de oxidação do par Cu(I)/Cu(II) e o segundo ao processo de oxidação Fe(II)(CN)5NO / Fe(III)(CN)5NO do complexo binuclear. O sistema SiCoNP foram observados dois pares redox distintos com os seguintes potenciais médios (Em); (Em)1 = 0,29 V e (Em)2 = 0,56 V vs Ag/AgCl, o primeiro foi atribuído ao processo redox do par Co(II)/Co(III) e o segundo ao processo redox Fe(II)(CN)5NO / Fe(III)(CN)5NO do complexo binuclear formado. O sistema SiCuNP foi sensível a concentração de hidrazina apresentando um limite de detecção e sensibilidade amperométrica de 3,07×10-4 mol L-1 e 5,84×10-6 A / mol L-1... / The objective of this work is summarized in three stages. 1 - The first stage functionalizes and characterizes the silica gel with 3-aminopropyltriethoxysilane groups. At this stage the material obtained (Si) was characterized by solid state Nuclear Magnetic Resonance techniques (24Si and 13C) and vibrational spectroscopy (FTIR). 2 - The second stage promotes the adsorption of copper (II) and cobalt (II) ions on the surface of the silica (Si). The materials obtained (SiCu and SiCo) were characterized by vibrational spectroscopy and cyclic voltammetry. 3 - The third stage prepares the reaction of the materials (SiCu and SiCo) with sodium nitroprusside to form the binuclear complex (SiCuNP and SiCoNP). These materials were characterized by vibrational spectroscopy and cyclic voltammetry. These materials were used to construct the electrode carbon paste and were tested for electrocatalytic oxidation of biologically important substances such as hydrazine and N-acetylcysteine using the cyclic voltammetry technique. It was observed that the electrode SiCuNP has two redox pairs in the potential (Em)1 = 0.34 V and (Em)2 = 0.76 V vs. Ag/AgCl, the first was attributed to the oxidation process of the pair Cu(I)/Cu(II) and the second to the oxidation process Fe(II)(CN)5NO / Fe(III)(CN)5NO of the binuclear complex. For the SiCoNP system, two distinct redox couples were observed with the following mean potentials (Em); (Em)1 = 0.29 V and (Em)2 = 0.56 V vs Ag/AgCl, the first one was assigned to the redox process of the Co(II)/Co(III) pair and the second one to the redox process Fe(II)(CN)5NO / Fe(III)(CN)5NO of the binuclear complex formed. The SiCuNP system was sensitive to the hydrazine concentration, exhibiting a detection limit and amperometric sensitivity of 3.07×10-4 mol L-1 and 5.84×10-6 A / mol L-1 respectively and was also... (Summary complete electronic access click below)

A produção de radicais de carbono \"in vivo\" durante a biotransformação da hidrazina foi demonstrada por ressonância para magnética eletrônica, utilizando o método do captador de spin. Eritrócitos de rato também oxidaram a hidrazina, formando radicais de carbono e nitrogênio, além de espécies reativas de oxigênio. Todas estas espécies, possivelmente formadas \"in vivo\", são potencialmente causadoras de dano a macromoléculas. Podem, por exemplo, iniciar reações secundárias formando radicais de componentes celulares, como ocorreu com a hemoglobina que foi oxidada a radicais tiil-hemoglobina em eritrócitos tratados com hídrazina. Radicais de carbono formados durante a biotransformação da hidrazina em animais expostos provêm necessariamente de substâncias endógenas e podem ser direta ou indiretamente responsáveis pela modificação ( alquilação ) de bases no DNA \"in vivo\". A hidrazona do formaldeído é descrita na literatura como um intermediário da alquilação induzida por hidrazina \"in vivo\". Células L 1210, catalase ou oxihemoglobina de rato foram capazes de formar radicais de carbono durante a oxidação da hidrazona do formaldeído. A oxidação da hidrazona do formaldeído pela catalase foi estudada \"in vítro\" e os radicais de carbono formados, identificados como radicais metila. A base modificada C8 -metil-guanina foi formada em animais expostos, como demonstrado por cromatografia líquida de alta eficiência associada à detecção eletroquímica, sugerindo que ocorreu alquilação do DNA por radicais metila durante a biotransformação da hidrazina \"in vivo\". / The production of carbon-centered radicais during hydrazine biotransformation \"in vivo\" was demonstrated by electron paramagnetic resonance ( EPR ) spin trapping technique. Rat red blood cells also oxidized hydrazine, forming carbon and nitrogen centered radicais, besides oxygen reactive speties. Ali these species, possibly formed \"in vivo\", are potentially harmful to macromolecules. For example, they can initiate secondary reactions in which the radicais from cell components are formed, as it occurred with hemoglobin, forming thiyl-hemoglobin radicais in the red blood cells treated with hydrazine. Carbon-centered radicais produced during the biotransformation of hydrazine in exposed animais must be derived from endogenous sources and may be directly or indirectly responsible for the modificaton ( alkylation ) of DNA bases \"in vivo\". The formaldehyde hydrazone is reported in the literature as an intermediate of hydrazine-induced alkylation \"in vivo\". L1210 cells, catalase and rat hemoglobin were able to produce carbon-centered radicais during the oxidation of the formaldehyde hydrazone. The oxidation of formaldehyde hydrazone by catalase was studied \"in vitro\" and the generated carbon-centered radicais were identified as methyl radicais. The modified base C8 -methylguanine was formed in exposed animais, as demonstrated by high performance liquid chromatography with electrochemical detection, suggesting that DNA alkylation by methyl radicais occurred during hydrazine biotransformation \"in vivo.\"

Compostos com alto conteúdo de hidrogênio, tais como hidrazina (N2H4) e íons borohidreto (BH4-), apresentam grande potencialidade como combustíveis em células a combustível ou em reformadores eletroquímicos para a geração de hidrogênio, uma vez que apresentam alta densidade de energia. Além disso, as reações de eletro-oxidação dessas espécies podem ser catalisadas por metais não nobres como Ni e Co, em eletrólito alcalino. Dessa forma, este projeto de pesquisa teve como objetivo a síntese e a investigação da atividade eletrocatalítica de eletrocatalisadores formados por nanopartículas de níquel e cobalto e por níquel em combinação com outro metal também ativo, como a platina, representados genericamente por NiO/C, Co3O4/C NiO-Pt/C, para a eletro-oxidação de hidrazina e de íons borohidreto. Os resultados eletroquímicos mostraram maiores atividades eletrocatalíticas, tanto para a eletro-oxidação de hidrazina quanto para íons borohidreto, para Co3O4/C em relação ao NiO/C, mas evidenciaram maior estabilidade para NiO/C. Tanto para NiO/C como para NiO-Pt/C, os experimentos mostraram que, em potenciais logo acima do de circuito aberto, a atividade eletrocatalítica origina-se da coexistência de espécies de Ni0 ou Pt0 e Ni-OH superficiais, onde a reação de eletro-oxidação de hidrazina é catalisada com efeito sinérgico bifuncional relacionado ao acoplamento de Ni-H ou Pt-H, gerado pela adsorção dissociativa de hidrazina (ou borohidreto), e Ni-OH, gerado pela descarga de OH- em baixos potenciais. Em altos sobrepotenciais, as correntes faradaicas aumentam significativamente e, para as duas reações, é proposto uma mecanismo de mediação de elétrons, no qual a hidrazina ou os íons borohidreto reduzem quimicamente o óxido de níquel ou de cobalto, com a geração de produtos destes combustíveis, e isto é seguido pela eletro-oxidação do metal, induzido pelo alto potencial do eletrodo, fechando o ciclo de mediação. Resultados de experimentos de DEMS online (Differential Electrochemical Mass Spectrometry), tanto para NiO/C ou Co3O4/C, quanto para NiO-Pt/C (somente para hidrazina neste caso), mostraram que as correntes faradaicas são seguidas pela geração do produto principal (N2 para o caso de hidrazina; BO2- para o borohidreto, sendo que este último não pode ser detectado por DEMS) em baixos sobrepotenciais e, em altos sobrepotenciais, o sinal do produto principal é acompanhado pelos sinais de H2 e de NH3, com comportamento similar. Este resultado evidencia que a reação de eletro-oxidação completa de hidrazina ou de íons borohidreto ocorre em maior extensão somente em baixos sobrepotenciais, sendo que, em altos sobrepotenciais, onde se tem a formação de óxidos de níquel ou de cobalto, as reações operam em maior extensão por vias incompletas de eletro-oxidação, para as quais tem-se a mediação de elétrons como mecanismo reacional. / High hydrogen content compounds, such as hydrazine (N2H4) and borohydride ion (BH4-) exhibit high prospect as fuel for fuel cells or electrochemical reformers for hydrogen generation, since they present high energy density. Moreover, their electro-oxidation reactions can be catalyzed on non-noble electrocatalysts, such as Ni and Co, in alkaline electrolyte. In this way, this project aimed the synthesis and the investigation of the electro-catalytic activity of nickel, cobalt and nickel/platinum nanoparticles based electrocatalysts, named as NiO/C, Co3O4/C and NiO-Pt/C, for hydrazine and borohydride electro-oxidation reactions. Electrochemical results showed high electrocatalytic activity of Co3O4/C for both reactions, (hydrazine and borohydride electro-oxidation), however NiO/C showed more stability. For both NiO/C and or NiO-Pt/C, the experiments showed that under potentials slightly above the open-circuit potential, the electrocatalytic activity comes from the co-existence of Ni0, Pt0 and Ni-OH on the surface. The hydrazine electro-oxidation reaction is catalyzed by a bi-functional synergistic effect related to the Ni-H or Pt-H coupling generated from dissociative adsorption of hydrazine (or borohydride), and Ni-OH, produced by OH- discharge in low potentials. In high overpotentials, the faradaic currents increase significantly for both reactions. An electron-mediated mechanism is proposed for this condition, where the hydrazine or borohydride ions reduces chemically the nickel or cobalt oxide, producing the reaction products from these fuels and, this is followed by the metal electro-oxidation, induced by the high potential of the electrode, completing the mediation cycle. For all electrocatalysts (only hydrazine for NiO-Pt/C), online DEMS (Differential Electrochemical Mass Spectrometry) results showed that the faradaic currents keep up with by the generation of the main product, in low potentials (N2 for hydrazine and BO2- for borohydride, but this last one cannot be detected by DEMS). In high overpotentials, the main product signal is followed by the signals, with similar behavior, of H2 and NH3. This result evidences that the complete hydrazine and borohydride electro-oxidation reactions preferentially occur in low overpotentials, whereas, in high overpotentials, when the nickel or cobalt oxides are present, the reactions occurs preferentially by incomplete pathways, in an electron-mediated mechanism.

Philosophiae Doctor - PhD / Ammonia has attracted attention as a possible fuel for direct fuel cells since it is easy to handle under low pressure, costs only slightly higher than methanol and can easily be cracked down into hydrogen and nitrogen. At low temperature, ammonia oxidation on noble metal electrodes is a sluggish reaction and efficient catalysts are required to convert ammonia to nitrogen and hydrogen at reasonable reaction rates. In this thesis, I present polycrystalline and oriented nanoalloys synthesised at room temperature in aqueous media and their catalytic effects on the oxidation of ammonia. The electro-oxidation of ammonia on palladium-goldsilver (PdAuAgNPs) ternary nanoalloys was systematically studied in alkaline solution of potassium hydroxide (KOH) by cyclic voltammetry (CV). The PdAuAg nanoalloys were prepared through a facile synthesis with ascorbic acid as a reductant and polyvinylpyrrolidone (PVP) as a stabilising agent from aqueous solutions of PdCh/HAuCI4.3H20/AgN03 mixtures. UV-visible spectroscopy was used to confirm the complete reduction of the metal ions; absorption peaks observed at 260 nm, 285 nm and 420 nm for Ag", Au3+ and Pd2+ ions respectively, disappeared after reduction indicating a complete reduction of the metal ions to zero-valent nanoparticles. High resolution transmission electron microscopy (HR TEM) revealed the formation of crystalline nonaggregated 25-35 nm sized nanoalloys. The elemental composition of the nanoalloys measured using energy dispersive X-ray spectroscopy (EDX) showed the presence of the three elements; Pd, Au and Ag. The well-dispersed non-agglomerated PdAuAg nanoalloys exhibited a reduced overpotential and a 33%, 400%,82% and 54% increase in current density for ammonia electro-oxidation compared to Pd, PdAg, PdAu nanoparticles and bare Pt electrode, respectively. The much improved current density of the well-dispersed PdAuAg nanoalloys is attributed to the increased electrochemically active surface area of the nanoalloys. This electro catalytic behaviour of the PdAuAg nanoalloys for ammonia oxidation in KOH solutions provides a promising route for development of low-cost and high performance electro catalyst for electro-oxidation of ammoniaMoreover, ammonia oxidation on platinum surfaces has been found to be a very structure sensitive reaction which takes place almost exclusively on Pt(100) surfaces. I report for the first time the preparation of sodium polyacrylate-capped Pt(100)Pd, pte 1OO)Au, pte 1OO)Ir, Pt(IOO)Rh, Pt(100)PdAu, Pt(100)IrAu, Pt(IOO)PdIr and Pt(IOO)RhAu nanoalloys. The reduction of the metal ions to nanoparticles was confirmed by UV-visible spectroscopy while the shapes and the structures of the nanoparticles were studied using HRTEM and CV. HRTEM analysis showed well distributed non-agglomerated 5-20 nm semi-spherical and cubic nanoalloys with lattice fridges on their surfaces indicating the crystalline nature of the nanoalloys. Pt(100) nanoalloy systems showed particles with triangular and cubic shapes. The existence of the preferentially cubic shaped nanoparticles in the samples indicated that the nanoalloys had some (100) sites orientation/a significant amount of (100) sites at their surfaces. The CV of the nanoparticles in the hydrogen adsorption/desorption region (-200 mV to 100 mV vs. Ag! AgCl) was used to obtain qualitative information about the surface structure of the nanoparticles. The voltammogram of oriented Pt(100) nanoparticles showed very clearly the presence of adsorption states associated with (110) sites, (100) domains and (l00) sites at -131 mV, -34 mV and 29 mV, respectively. The companson of this voltammetric profile with that obtained for a Pt(100) single crystal electrode clearly points out that the synthesised Pt nanoparticles have a high density of (100) sites. However, the peak that was observed at 29 mV in the CV of Pt(100) nanoparticles was not present in the vo ltammo grams of the Pt(100) nanoalloy systems confirming the formation of the nanoalloys. The results reported in this work demonstrate the importance of controlling the intrinsic structural properties of Pt nanoparticles; in terms of nature of the active sites and the effect of adding adatoms (such as Au, Pd, Rh, Ir) in order to understand their catalytic properties. The electrochemical activities of these nanoparticles for ammonia oxidation in basic medium showed an increase of over 100% current density compared to Pt electrode. Pt(lOO)RhAu nanoalloys showed the highest catalytic properties while Pt(lOO)PdAu had the lowest as shown in the trend: Pt(lOO)RhAu > Pt(lOO)PdIr > Pt(lOO) > Pt(lOO)IrAu > Pt(lOO)Pd> Pt(lOO)Rh > Pt(lOO)Au > Pt(lOO)Ir > Pt(lOO)PdAu. The synthesised oriented nanoalloys were further interrogated towards the oxidation of hydrazine as a fuel for hydrazine fuel cells. The oriented Pt(lOO) nanoparticles and Pt(lOO) nanoalloy systems exhibited over 1000% increase in current density and reduced oxidation overpotential compared to bare glassy carbon electrode. These excellent catalytic properties are attributed to the increased surface area and the presence of (100) sites which favour the oxidation of hydrazine.

Based on the success of diacyl-tert-butylhydrazines RH-5849 and RH-1266 in controlling agricultural crop pests, we endeavored to synthesize our own diacylbenzyl- and arylhydrazine derivatives for use against the malaria vector Anopheles gambiae. In the process of producing a library of compounds for assay against An. gambiae, it became clear that employing regioselective acylation techniques (in molecules that feature two nucleophilic, acyclic nitrogen atoms α to one another) would be imperative. Synthesis of the library derivatives proceeded rapidly and after topical assay, we found three compounds that were more toxic than the RH-series leads. One of the three displayed an LD50 value of half that of RH-1266, though patch clamp assay concluded that toxicity was not necessarily linked to inhibition of mosquito K+ channel Kv2.1. The acylation of monoarylhydrazines appears simple, but its regioselectivity is poorly understood when assumed as a function of basicity correlating to nucleophilic strength. We determined the ratio of the rate constants for distal to proximal N-acylation using 19F NMR spectroscopic analysis of reactions of 4-fluorophenylhydrazine with limiting (0.2 equiv) acylating agent in the presence of various bases. Acid anhydrides gave consistent preference for distal acylation. The selectivity of acylation by acyl chlorides when using pyridine gives strong distal preference, whereas use of triethylamine or aqueous base in conjunction with aroyl chlorides showed a moderate preference for proximal acylation. This observation yielded a convenient one-step method to synthesize proximal aroylarylhydrazines in yields comparable or superior to that provided by the standard three-step literature approach. Combined with NMR evidence of the distal nitrogen as the unambigiously stronger base of the two nitrogens, we propose a single electron transfer mechanism that predicts the regiochemistry of arylhydrazines toward acylating agents better than the nucleophilicity model based on pKa values. While synthesizing the acylhydrazine library for assay against An. gambiae, NMR spectroscopy revealed rotational isomerisms of two types: chiral helicity (M)/(P) and acyl (E)/(Z)-isomerism due to hindered rotation. Variable temperature NMR allowed the measurement of N-N bond rotational barriers, as well as estimate the barrier of (E)/(Z) interconversion. We obtained the X-ray crystal structures of four diacylhydrazines to test this hypothesis and revealed both the twist conformation around the N-N bond axis and (E)/(Z)-isomerism around the proximal acyl group. Computation (which agreed with the crystal structures) allowed us to estimate which (E)/(Z)-isomers were most likely being observed in solution at room temperature by NMR spectroscopy. In addition, we were able to calculate transition structures corresponding to N-N bond rotational barriers of (E,Z)- and (Z,Z)-isomers of model molecules and rationalize the difference in coalescence temperatures between (E,Z)- and (Z,Z)-isomers. / Ph. D.

O processo de isquemia-reperfusão é responsável pela geração de um dano agudo em uma série de órgãos do corpo humano, e, no coração, é o principal causador da doença crônica conhecida por insuficiências cardíaca. Atualmente não existe nenhuma opção terapêutica disponível na prática clínica contra esta injúria. Com o objetivo de desenvolver uma nova estratégia de combate a este dano, no presente trabalho investigamos a promessa da aplicação da recém-descoberta via UPRam num modelo de hipóxia reoxigenação in-vitro, sem obter sucesso. Contudo, os resultados gerados nestes experimentos forneceram pistas de que o uso do desacoplador CCCP é capaz de reduzir o dano deste insulto, porém o mecanismo celular responsável por esta proteção permanece desconhecido. Tentativas de desvendar este mecanismo utilizando a via lisossomal-autofágica ou a clivagem de OPA-1 falharam, mas produziram importantes insights a respeito do papel da protease mitocondrial OMA-1 no processo de hipóxia-reoxigenação, abrindo caminho para novos estudos subsequentes. / Ischemia-reperfusion injury is a process that occurs in many human organs including the heart, where it is the main trigger to heart failure, a chronic disease that kills over 40% patients only five years following the first diagnosis. Despite the bulky research on the subject, there is no available therapy on clinical practice against this insult. Attempting to develop a novel strategy to mitigate this damage, we investigated if the pro-survival effect of the recently discovered UPRam pathway could be protective in an in-vitro model of ischemia reperfusion. Despite the negative results regarding its conservation on mammalian cells, treatment with the mitochondrial uncoupler CCCP was proven to reduce cell death under this process, but the cellular mechanism responsible for this protection remained elusive. Aspiring to unravel this cellular response, we tested whether autophagy or OPA-1 cleavage was capable of abrogating the verified protection, but the results came back negative. Regardless of that, the behavior of OMA-/- cells over H/R stress has given new insights on novel strategies comprising I/R injury abrogation.

No description available.