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The earliest landmark in computer technology was construction of the Electronic Numerial Integrator and Computer, ENIAC. Computational switching was performed with vacuum tubes and relays, rather large in size, making this computer rather unwieldy. The next milestone came with the integration of transistors into computers as the switching component. Since then, transistors have been miniaturised dramatically, resulting in the amount of components integrated on a computer chip increasing logarithmically with time. The components are nowadays so small and so densely packed that problems with leak currents and cross-talk can arise and the lower limit for transistor size will soon be reached. In order to meet increasing demands on the size and performance of electronics, a new paradigm is due – the molecular electronics approach. Oligothiophenes have been shown to possess the physical and chemical characteristics required for electron/energy transport in molecular systems. However oligothiophenes must be electronically coupled to other components within a molecular circuit for them to be functional. In this work, different modes of incorporation of [2,2’]-bipyridinyl functionalities onto the ends of prototypic oligothiophene wires have been examined. The bipyridine connectors allow complexation to metal centres which can then function as a source or sink of electrons in the circuit. Ruthenium tris-bipyridine complexes, in particular, possess interesting electrochemical and photophysical characteristics, making them suitable for use in molecular electronics. This thesis reports synthetic strategies to a range of novel ligands based on the [2,2’]-bipyridinyl system, together with a study of the redox and fluorescence properties of their ruthenium tris-bipyridine complexes. The mode of connection between the chelating bipyridine and the first member of the oligothiophene chain was found to have a profound effect upon the fluorescence lifetimes and intensities of the resulting complexes. The discovery of complexes exhibiting long and intense fluorescence (a requirement for directed electron/energy transfer within molecular networks) thus forms an important design element in future prototypes.

Orientador: Vanderlan da Silva Bolzani / Coorientador: Ian Castro Gamboa / Banca: Cintia Duarte de Freitas Milagre / Banca: Adriano Defini Andricopulo / Banca: Fernando Antônio Santos Coelho / Banca: Alcindo Aparecido dos Santos / Resumo: As leishmanioses englobam um espectro de doenças que afetam o ser humano e outros mamíferos nas regiões tropicais e subtropicais do planeta. São causadas por pelo menos 20 tipos de parasitas pertencentes ao gênero Leishmania, e apresentam diversas e complexas manifestações clínicas. Podem ser encontradas em mais de 88 países, sendo que o Brasil é um dos países endêmicos onde a doença está mais disseminada. Em 2010 foram confirmados 21.981 casos de leishmaniose tegumen-tar e 3536 de leishmaniose visceral, com 219 mortes. No mundo cerca de 350 mi-lhões de pessoas estão expostas à infecção e acredita-se que cerca de 12 milhões estejam infectadas, com cerca de 1-2 milhões de novos casos por ano e 60 mil óbi-tos. Pensando nisso, o presente estudo visou obter novas substâncias candidatas a serem utilizadas no combate as chamadas "Doenças Tropicais Negligenciadas", mais especificamente a Leishmaniose. Neste trabalho foram sintetizados doze aná-logos de meroterpenos, sendo nove compostos inéditos e ainda os compostos natu-rais isolados de Psidium guajava (psidial A, guajadial e pisguadial B), utilizando uma rota curta e linear e com rendimento global em torno de 20%. Um estudo sobre o mecanismo da reação de cicloadição [4+2] possibilitou determinar as barreiras de energia envolvidas nas transformações e permitiu compreender algumas limitações da metodologia empregada. Nos testes biológicos, os análogos sintéticos se mostra-ram promissores para combater a forma promastigota de Leishma... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Leishmaniasis encompasses a spectrum of diseases that affect humans and other mammals in the tropical and subtropical regions of the planet. They are caused by at least 20 types of parasites belonging to the genus Leishmania, and present diverse and complex clinical manifestations. They can be found in more than 88 countries, and Brazil is one of the endemic countries where the disease is most widespread. In 2010, 21,981 cases of tegumentary leishmaniasis and 3536 cases of visceral leish-maniasis were confirmed, with 219 deaths. Around 350 million people worldwide are exposed to the infection and an estimated 12 million are believed to be infected, with about 1-2 million new cases per year and 60,000 deaths. With this in mind, the pre-sent study aimed to obtain new candidate substances to be used in the fight against "Neglected Tropical Diseases", more specifically Leishmaniasis. In this work, twelve meroterpene analogs were synthesized, with nine new compounds and the natural compounds isolated from Psidium guajava (psidial A, guajadial and pisguadial B) using a short and linear route with a global yield of around 20%. A study of the mechanism of the cycloaddition reaction [4 + 2] made it possible to determine the energy barriers involved in the transformations and allowed to understand some limitations of the methodology used. In biological tests, synthetic analogues were shown to be promising to combat the promastigote form of Leishmania infantum, with EC50 values between ... (Complete abstract click electronic access below) / Doutor

This thesis describes the development of a synthetic route towards daphlongeranine B, an alkaloid isolated from the fruits of Daphniphyllum longeracemosum, by utilising an intramolecular Michael addition to form its unique tricyclic core. <strong>Chapter 1</strong> gives a general introduction to the family of Daphniphyllum alkaloids together with some recent examples, from the literature, illustrating some synthetic attempts towards structurally similar alkaloids. This chapter also features our retrosynthetic analysis of daphlongeranine B. <strong>Chapter 2</strong> details the synthesis of the model spirocyclic enone 72 which was the vital building block needed to investigate the key intramolecular Michael addition. This key reaction was then successfully validated and access to the unique tricyclic core 64 of daphlongeranine B was made possible. <strong>Chapter 3</strong> expands the scope of the key intramolecular Michael addition step. This chapter first describes a synthetic route to the Î2-substituted spirocyclic enone 112 and subsequently validates the key intramolecular Michael addition step to give the tricyclic core 138 of daphlongeranine B. <strong>Chapter 4</strong> details a synthetic route towards the spirocyclic fragment 141 by utilising a Baker's yeast reduction and a tandem addition/cyclisation reaction.

As cumarinas são estruturas interessantes aos olhos da química medicinal, apresentando diversas atividades biológicas sobre os mais variados alvos. Neste trabalho, em um primeiro momento, realizamos a extração com CO2 em meio supercrítico das cumarinas de Pterocaulon balansae, planta nativa do Rio Grande do Sul que apresenta em sua composição grandes quantidades destes compostos. A extração com CO2 supercrítico apresentou rendimentos satisfatórios em massa de sete cumarinas previamente descritas para estas espécies. Dentre estes se destacam os compostos majoritários 7-(2,3-epoxi-3-metil-3-butiloxi)-6-metoxicumarina e 5,6-dimetoxi-7-(2’,3’-epoxi-3-metilbutiloxi) cumarina. Realizamos também a síntese de 4-metilcumarinas através de reação de Pechmann, obtendo o composto LaSOM 77 (7-hidroxi-4-matilcumarina) com excelentes rendimentos, onde realizamos uma diversificação estrutural através da adição de um linker e posteriormente a síntese de triazóis através de “Click Chemistry”. Para tanto, utilizamos uma biblioteca de 35 alcinos disponíveis comercialmente e outros 3 sintetizados em nosso laboratório. Sendo assim, obtivemos uma biblioteca de 38 híbridos cumarina-triazol que apresentaram excelentes rendimentos, em tempos reacionais que variaram entre 20 e 50 minutos de reação sob irradiação de microondas. Os testes biológicos preliminares frente a linhagens cancerígenas indicaram que os compostos sintetizados apresentam potencial utilização como anticancerígenos, sendo ativos frente a linhagens celulares de câncer de pulmão, fígado e mama, apresentando baixa toxicidade em células sadias. A partir das investigações teóricas e experimentais relacionadas à este trabalho foi produzido um artigo de revisão, intitulado “New insights into the chemistry and antioxidante activity of coumarins” está aceito pelo periódico Current Topics in Medicinal Chemistry. / Coumarins are interesting structures for the medicinal chemistry, because present several biological activities. At first, we performed the supercritical CO2 extraction from Pterocaulon balansae, a plant native from Rio Grande do Sul, which has in its composition large amounts of these compounds. The extraction with supercritical CO2 showed satisfactory yields of seven coumarins previously described for this species. Among these compounds the coumarins 7-(2,3-epoxy-3-methyl-3-butyloxy)-6-methoxycoumarin e 5,6-dimethoxy-7-(2’,3’-epoxy-3-methylbutyloxy) coumarin are the majority compunds. We also performed the synthesis of 4-methylcoumarins using Pechmann reaction, obtaining the compound LaSOM 77 (7-hydroxy-4-methyl-coumarin) in excellent yield and perfomed the structural diversification trougth the addition of a linker and subsequentely synthesis of 1,2,3-triazoles by Click Chemistry. Therefore, was used a colection of 35 commercialy available alkynes and other 3 synthesized in our laboratory to obtain a colection of 38 coumarin-triazole hybrids in excellent yields and time of reaction ranging betwenn 20 and 50 minutes under microwave radiation. Preliminary biological tests against cancerous strains indicated that the synthesized compounds have potential use as anticancer agents against cell lines of lung, liver and breast cancer. From the theorical and experimental data from this work, one review paper was produced: The article is intitled “New insights into the chemistry and antioxidante activity of coumarins” is accepted to the journal "Current Topics in Medicinal Chemistry".

abstract: Humanity’s demand for energy is increasing exponentially and the dependence on fossil fuels is both unsustainable and detrimental to the environment. To provide a solution to the impending energy crisis, it is reasonable to look toward utilizing solar energy, which is abundant and renewable. One approach to harvesting solar irradiation for fuel purposes is through mimicking the processes of natural photosynthesis in an artificial design to use sunlight and water to store energy in chemical bonds for later use. Thus, in order to design an efficient energy conversion device, the underlying processes of the natural system must be understood. An artificial photosynthetic device has many components and each can be optimized separately. This work deals with the design, construction and study of some of those components. The first chapter provides an introduction to this work. The second chapter shows a proof of concept for a water splitting dye sensitized photoelectrochemical cell followed by the presentation of a new p-type semiconductor, the design of a modular cluster binding protein that can be used for incorporating catalysts, and a new anchoring group for semiconducting oxides with high electron injection efficiency. The third chapter investigates the role of electronic coupling and thermodynamics for photoprotection in artificial systems by triplet-triplet energy transfer from tetrapyrroles to carotenoids. The fourth chapter describes a mimic of the proton-coupled electron transfer in photosystem II and confirms that in the artificial system a concerted mechanism operates. In the fifth chapter, a microbial system is designed to work in tandem with a photovoltaic device to produce high energy fuels. A variety of quinone redox mediators have been synthesized to shuttle electrons from an electron donor to the microbial system. Lastly, the synthesis of a variety of photosensitizers is detailed for possible future use in artificial systems. The results of this work helps with the understanding of the processes of natural photosynthesis and suggests ways to design artificial photosynthetic devices that can contribute to solving the renewable energy challenge. / Dissertation/Thesis / Doctoral Dissertation Chemistry 2015