Dissertations / Theses on the topic 'Porphyrins and derivates'

L’impression moléculaire de polymères est une technique utile pour créer des récepteurs artificiels capables de lier sélectivement des substrats. Cette propriété de reconnaissance rend les polymères à empreintes moléculaires particulièrement intéressants pour développer des catalyseurs macromoléculaires. Notre objectif a ainsi été d’accéder à un catalyseur supramoléculaire recyclable et capable d’oxyder des dérivés du soufre dans des conditions hétérogènes en présence d’un oxydant doux et éco-compatible tel que le peroxyde d’hydrogène. Compte-tenu de l’engagement du laboratoire dans la lutte contre les armes chimiques, nous avons décidé d’orienter nos travaux vers la mise au point d’un système catalytique qui serait utile pour la décontamination de surfaces ou de matériels, suite à l’exposition à certains composés dont la détoxification passe par l’oxydation sélective d’un sulfure. Nous avons ainsi préparé un MIP à base de porphyrine dont nous avons testé l'efficacité dans l'oxydation de divers sulfures d’intérêt. Les conditions douces utilisées pour la catalyse ont ainsi permis de contrôler le degré d’oxydation d’un simulant de l’ypérite, en obtenant avec une très grande sélectivité le dérivé sulfoxyde, sans que le dérivé sulfone qui serait tout aussi toxique que l’arme chimique elle-même ne se forme. Aves des structures plus proches de celle du VX, nous avons montré qu’il était possible d’oxyder régiosélectivement le soufre, et mis en évidence l’intérêt de ce procédé pour faciliter le clivage d’une liaison C-S. Cette approche représente donc une stratégie de décontamination intéressante qu’il conviendra d’évaluer dans le cas de véritables agents de guerre chimique<br>Molecular imprinting polymer is a useful technique for creating artificial receptors able of selectively binding substrates. These recognition properties are particularly interesting for developing macromolecular catalysts. Our aim was to access to a reusable supramolecular catalyst able of oxidizing sulfur derivatives under heterogeneous conditions in the presence of a mild and eco-sustainable oxidant such as hydrogen peroxide. Given the expertise of the team, we decided to focus our work on the development of a catalytic system for the decontamination of surfaces or equipment, after an exposure to compounds that can be detoxified by a selective oxidation of sulfides. Thus, we prepared a porphyrin-based MIP that we tested in the oxidation of various sulfides. The mild conditions used for the catalysis allowed a control of the oxidation degree of a simulant of yperite, leading to a great selectivity the sulfoxide derivative, and avoiding the toxic sulfone formation. With other structures similar to VX, we showed that it is possible to regioselectively oxidize the sulfur atom, and highlighted the interest of this process to facilitate the cleavage of a C-S bond. This approach is then an interesting decontamination strategy that will be evaluated in the future to the case of true chemical warfare agents

Mestrado em Química<br>Neste trabalho é descrita a síntese de porfirinas regulares e N-confusas com o objetivo da realização de estudos acerca da sua eficiência como fotossensibilizadores (PSs) em terapia fotodinâmica (PDT) e a influência desta no splicing alternativo do mRNA. Os derivados porfirinicos foram preparados tendo como estrutura base a 5,10,15,20-tetraquis(1-metilpiridinio-4-il)porfirina. Inicialmente irá ser realizada uma breve introdução sobre os macrociclos tetrapirrólicos, nomeadamente sobre porfirinas. Segue-se o capítulo 2 onde há a descrição sintética dos derivados porfirínicos usados neste trabalho. Desta forma, através das condições estabelecidas por Lindsey foram sintetizadas duas porfirinas: 5,10,15,20-tetraquis(4-bromometilfenil)-2-aza-21-carboporfirina e a 5,10,15,20-tetraquis(4-bromometilfenil)porfirina e procedendo-se à sua cationização com piridina que originou os derivados 5,10,15,20-tetraquis(4-(piridinio-1-il-metil)fenil)-2-aza-21-carboporfirina e 5,10,15,20-tetraquis(4-(piridinio-1-il-metil)fenil)porfirina. A formação das porfirinas neutras ocorreu com baixo rendimento, mas a sua cationização foi conseguida com rendimentos acima dos 80%. Neste mesmo capítulo ainda são apresentadas as caracterizações fotofísicas de todos os derivados porfirínicos, nomeadamente fluorescência e geração de oxigénio singleto. As porfirinas regulares foram aquelas que demonstraram bons rendimentos quânticos de fluorescência e capacidade para gerar oxigénio singleto em DMF. No capítulo 3 são descritos todos os estudos biológicos realizados neste trabalho. Inicialmente foram realizados estudos de viabilidade celular em células MCF-7 e HeLa usando o teste com WST-1 e ATPliteTM e como PS de referência a 5,10,15,20-tetraquis(1-metilpiridinio-4-il)porfirina. Foram realizados estudos de concentração (0.1 μM-5.0 μM) e tempo de irradiação (0, 5, 10 e 15 min). A 5,10,15,20-tetraquis(4-(piridinio-1-il-metil)fenil)porfirina revelou ser o melhor PS, tendo sido selecionado um tempo de irradiação de 15 min e uma concentração até 5 μM para o estudos subsequentes. Os estudos de localização subcelular e uptake revelaram que a 5,10,15,20-tetraquis(4-(piridinio-1-il-metil)fenil)porfirina entra nas células mas não se localiza no núcleo como acontece com o controlo positivo. São ainda descritos estudos acerca do tipo de morte celular que as células podem sofrer depois da PDT com estes PSs. Por fim os estudos da influência da terapia fotodinâmica no splicing alternativo mostrou que a 5,10,15,20-tetraquis(4-(piridinio-1-il-metil)fenil)porfirina e a 5,10,15,20-tetraquis(1-metilpiridinio-4-il)porfirina parecem induzir um ligeiro splicing alternativo do mRNA.<br>In this work the synthesis of regular and N- confused porphyrins with the objective of assessing its efficiency as photosensitizers (PSs) in photodynamic therapy (PDT) and its influence in alternative splicing of mRNA is described. The porphyrin derivatives were prepared having as a template the 5,10,15,20-tetrakis(1-methylpyridynium-4-yl)porphyrin. Initially, a brief introduction about tetrapyrrolic macrocycles, namely about porphyrins will be done. Then, chapter 2 will follow with the synthetic description of the porphyrin derivatives used in this work. Through Lindsey conditions, two porphyrins were synthesized: 5,10,15,20-tetrakis(4-bromomethylphenyl)-2-aza-21-carbaporphyrin; 5,10,15,20-tetrakis(4-bromomethylphenyl)porphyrin and then we proceeded to their cationization with pyridine to give: 5,10,15,20-tetrakis(4-(pyridynium-1-yl-methyl)phenyl)-2-aza-21-carbaporphyrin and 5,10,15,20-tetrakis(4-(pyridynium-1-yl-methyl)phenyl)porphyrin. The formation of the neutral porphyrins occurred with low yield but its cationization was achieved with yields higher than 80%. In the same chapter, the photophysical characterization of all porphyrins, namely singlet oxygen production and fluorescence quantum yield were described. The regular porphyrins demonstrated good fluorescence quantum yields and ability to generate singlet oxygen in DMF. In chapter 3, all the biological assays done in this work are described. Initially, cellular viability studies were done in MCF-7 and HeLa cells using the WST-1 reagent and ATPliteTM and as PSs reference the 5,10,15,20-tetrakis(1-methylpyridynium-4-yl)porphyrin. Studies of concentration (0.1 μM-5.0 μM) and irradiation time (0, 5, 10 and 15 min) were also done. The 5,10,15,20-tetrakis(4-(pyridynium-1-yl-methyl)phenyl)porphyrin showed to be the best PS and 15 min irradiation and a concentration up to 5 μM for the following studies were selected. The subcellular localization and uptake studies revealed that 5,10,15,20-tetrakis(4-(pyridynium-1-yl-methyl)phenyl)porphyrin can enter the cells but it is not localized in the nucleus, contrary to 5,10,15,20-tetrakis(1-methylpyridynium-4-yl)porphyrin. The studies regarding type of cell death that cells undergo after PDT treatment were also assessed. At last, the 5,10,15,20-tetrakis(4-(pyridynium-1-yl-methyl)phenyl)porphyrin and 5,10,15,20-tetrakis(1-methylpyridynium-4-yl)porphyrin seemed to induce a small alternative splicing of mRNA.

A TFD está baseada no uso de um fármaco fotossensível que, uma vez ativado por luz visível e na presença do oxigênio, induz a produção de espécies reativas de oxigênio tais como o radical peroxila, o ânion radical superóxido e o radical hidroxila (Tipo I) ou oxigênio singlete (Tipo II), que atuam diretamente sobre os sistemas biológicos, induzindo a morte da célula por processo necrótico ou apoptótico. A maioria dos tipos de tumores responde ao tratamento e os resultados são promissores. Entretanto, órgãos altamente pigmentados e vísceras maciças (fígado, baço, rins e medula óssea) impedem a penetração da luz visível para o tratamento, o que representa um tipo de resistência aos protocolos da Terapia Fotodinâmica. Torna-se necessário, portanto, procurar por novos agentes fotossensibilizadores. Estudos mostraram que a ação fotodinâmica induz mudanças diretas na membrana celular que levam a um desequilíbrio na homeostase iônica celular (íons sódio, potássio e cálcio), o que certamente leva a um dano no transporte de proteínas da membrana plasmática e, em última análise, a um stress osmótico irreversível. Neste trabalho, procurou-se determinar a potencialidade do uso da 5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxaciclopentadecane-2-aminometil)2,3,-5,6-tetrafluoro)fenil]-porfirina (H2C4P), e o Zn(II)5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxaciclopentadecane-2-aminometil)2,3,5,6-(tetrafluoro)fenil]-porfirinato (ZnC4P) como fármaco fotossensível. Avaliou-se também a zinco ftalocianina associada ao éter de coroa onde, graças à presença do éter de coroa, pôde-se observar uma potencialização da ação fotodinâmica. Nos estudos fotofísicos e fotoquímicos, observou-se que os fármacos porfirínicos possuem importantes propriedades espectroscópicas para a TFD. O rendimento quântico de produção de oxigênio singlete foi medido e o valor encontrado para H2C4P ( = 0,62) foi maior que o valor encontrado para ZnC4P ( = 0,46). Os valores de rendimento quântico de produção dos estados excitado tripletes (T) para ZnC4P foi da ordem de 0,73 ± 0,06 e para H2C4P foi da ordem de 0,63 ± 0,05, mostrando que o mecanismos Tipo II para a porfirina base livre H2C4P é dominante e para o fotossensibilizador metalado ZnC4P tem-se Tipo I dominante. Ambos os sistemas apresentaram uma eficiente ação fotodinâmica nos estudos com a linhagem de células J774-A.1. Fez-se uso de sondas fluorescentes para monitorar a distribuição e alteração na homeostase de íons através da membrana plasmática. Esses estudos mostraram que a presença dos ligantes éter de coroa na estrutura da porfirina, atuando concomitantemente à ftalocianina, potencializa a ação fotodinâmica. Observou-se que o 18-crow-6 éter de coroa minimiza a diferença de potencial da mesma ordem de magnitude de quando está associado à ZnPc em uma formulação lipossomal (da ordem de 50%), o que mostra que a ZnPc não interfere na formação dos canais de íons potássio formados. Os resultados indicaram um grande potencial de aplicação do ligante éter de coroa associado ou ligado covalentemente ao fármaco no uso da TFD, visto que o éter de coroa não modificou as características fotofísicas e fotoquímicas dos fotossensibilizadores, uma nova perspectiva no que chamamos de Terapia Fotodinâmica Sinérgica.<br>Photodynamic Therapy (PDT) is based on the use of a photosensitive drug which, once activated by visible light and in the presence of oxygen, induces the production of several reactive species of oxygen, such as the peroxyl radical, superoxide anion and hydroxyl radical (Type I) or singlet oxygen (Type II), which act directly over the biological systems inducing the cell death, through a necrotic or apoptotic process. Most of the types of tumor respond to the treatment and the results are prosperous. However, highly pigmented organs and massive viscera (kidneys, spleen, liver and bone marrow) block the penetration of the visible light for the treatment, what represents a kind of resistance towards the Photodynamic Therapy protocols. Hence, it is necessary to look for new phosensitizing agents. Studies have shown that the photodynamic action induces direct changes in the cell membrane that lead to an unbalance in the cell ionic homeostasis (sodium, potassium and calcium ions), what certainly causes damage to the plasmatic membrane protein transport, and in a final analysis, irreversible osmotic stress. In this work, we aimed at determining the potentiality of the use of the 5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxacyclopentadecane-2-aminometil)2,3,- 5,6-(tetrafluoro)phenyl] porphyrin (H2C4P), and the Zn(II)5,10,15,20-tetrakis[4- (1,4,7,10,13-pentaoxacyclopentadecane-2-aminomethyl)2,3,5,6-(tetrafluoro)- xvi phenyl]-porphyrinate (ZnC4P) as a photosensitive drug. We evaluated also the phytalocianine zinc associated to the crown ether where, due to the presence of the crown ether, we could observe a potentialization of the photodynamic action. In the photophysical and photochemical studies, we observed that the porphyirinic drugs present important spectroscopic properties to PDT protocol. The singlet oxygen production quantum yield was measured and the value found for H2C4P (FD = 0.62) was higher than that one found for ZnC4P (FD = 0.46). The value of the quantum yield of the production of the triplet excited states (FT) for ZnC4P was 0.73, and for H2C4P it was 0.63, showing that the mechanism Type II for the free-base porphyrin H2C4P is the dominant effect, and for the ZnC4P metallated photosensitizer, Type I process is the dominant one. Both systems present an efficient photodynamic action in the studies with the J774-A.1 cell strain. We used fluorescent probes to monitor the distribution and alteration of the ionic homeostasis through the plasmatic cell membrane. These studies showed that the presence of the crowned-ether ligants in the structure of the porphyrine, acting together with the dye structure, potentializes the photodynamic action. We observed that the 18-crow-6 crown ether decrease the difference in the transmembrane electrical potential in the same order of magnitude when it is associated to the ZnPC in a liposome formulation, (around 50%), what shows that the ZnPC does not interfere in the action of the potassium ion channels. xvii These results indicated a great potential of application of the crowned-ether ligant associated or covalently connected to the drug in the use of PDT, protocol once the crown ether structure did not modify the photophysical and photochemical characteristics of the photosensitizers, a new perspective in what we call Synergic Photodynamic Therapy.

Made available in DSpace on 2015-05-14T12:59:56Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 8420094 bytes, checksum: e38d9fce0fc67703d2f3e878474b7c32 (MD5) Previous issue date: 2013-02-27<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES<br>The Piper L. genus is the largest one among the Piperaceae. Containing at least 1000 species, they are located mainly on the neotropical region of Earth and it draws our attention due to its medical, economical, chemical and cultural properties, such as anti-inflamatory, antibacterial and fungicide actions. Piper genus species have been becoming research sources for specific classes of secondary metabolites which play an important role concerning biological activities, including alkaloids, amides, chalcones, chromenes, flavonoids, lignans, terpenes, cyclopentanediones, steroids, porphyrin derivatives and benzoic acid derivatives. Piper caldense C. DC., which is commonly known as Pimenta D arda , is used in Paraíba as sedative, snake venom antidote, anti-toothache agent, and as active in located pain treatments through the use of compresses. This research reports the phytochemical study of P. caldense C. DC. leaves and fruits. Through usual chromatographic methods and spectroscopic techniques such as IR and one and two-dimensional ¹H and ³CNMR techniques and comparison with literature data it was possible to isolate and identify an mixture of the β-sitosterol and sitgmasterol steroids, besides porphyrin substances: 15-hydroxy-A-pophyrinlactone and a phaeophytin. Those fractions were obtained from crude ethanolic extract of P. caldense C. DC. leaves. Three benzoic acid derivatives were isolated from the hexane extract of P. caldense C. DC. fruits. From its leaves and fruits it was possible to obtain seven compunds commonly found it many vegetal species, but for the first time stated from P. caldense C. DC. The hexane and dichloromethane fruit extracts and isolated substances were submitted to microbiological assay and antifungal activites were detected concerning Candida genus yeast. This test is being done for the first time in the fruits of the studied species.<br>O gênero Piper L. é o maior da família Piperaceae, compreendendo pelo menos 1000 espécies, que se encontram distribuídas especialmente na região neotropical do globo terrestre e se destaca por suas propriedades medicinais, econômicas, químicas e culturais (anti-inflamatória, antibacteriana, anestésia e fungicida, dentre outros). Espécies do gênero Piper têm-se tornado fontes de pesquisa de classes específicas de metabólitos secundários com marcantes atividades biológicas, incluindo alcaloides, amidas, chalconas, cromenos, flavonoides, lignanas, terpenos e ciclopentanodionas, esteroides, derivados porfirínicos e derivados do ácido benzoico. Piper caldense C. DC., conhecida popularmente como pimenta d arda , é utilizada na Paraíba como sedativa, antídoto para picadas de cobras, para dores de dente, bem como na forma de compressa no local afetado para alívio da dor. Este trabalho reporta o estudo fitoquímico das folhas e frutos de P.caldense C. DC. Utilizando-se métodos cromatográficos usuais e técnicas espectroscópicas de IV e RMN de 1H e 13C uni e bidimensionais e a comparação dos dados com a literatura foi possível isolar e identificar do extrato etanólico bruto das folhas de Piper caldense C.DC., uma mistura de esteroides, o β-sitosterol e o estigmasterol, e duas substâncias porfirínicas, a 15-hidroxi-porfirionolactona A e a feofitina a, e, do extrato hexânico dos frutos, três derivados do ácido benzoico, compreendendo ao total sete substâncias, descritas pela primeira vez em Piper caldense C. DC. Os extratos hexânico e diclorometânico dos frutos e suas substâncias isoladas foram submetidos a ensaios microbiológicos, apresentando atividade antifúngica frente a leveduras do gênero Candida. Este ensaio está sendo feito pela primeira vez nos frutos da espécie estudada.

Uma série de oito derivados porfirínicos monocatiônicos, na forma de base-livre e metalados com Zn(II), e tendo grupos metila ou [Ru(bipy)2Cl]+ ligados ao átomo de nitrogênio do substituinte piridil em uma das posições meso do anel, foram sintetizadas e caracterizadas, visando sua aplicação como fotossensibilizadores no tratamento de tumores de pele por TFD. Além de possuírem características anfifílicas que favorecem a sua interação com membranas biológicas, os compostos apresentaram um elevado rendimento quântico de formação de oxigênio singlete, principalmente os derivados metilados das porfirinas base-livre. A baixa solubilidade em meio aquoso, fator limitante da utilização como fotossensibilizadores, foi superada por meio do encapsulamento dos mesmos em micro e nanocápsulas poliméricas, pelo método de coacervação. Duas formulações, uma baseada em hidroxietilcelulose (HEC) e outra na mistura atelocolágeno marinho/goma xantana (ACM), foram preparadas e suas eficiências fotodinâmicas e citotoxicidade frente à células HeLa determinadas. As formulações de ACM mostraram ser não-tóxicas, enquanto os preparados com HEC apresentaram uma pequena, mas significativa citotoxicidade no escuro. Por outro lado, todas as formulações se tornaram tóxicas quando irradiadas com laser de 650 nm ou luz branca proveniente de lâmpada de mercúrio. Dentre as formulações preparadas, as mais ativas foram aquelas preparadas com os derivados porfirínicos base-livre metilados em ACM, provavelmente em virtude da maior eficiência de entrega do composto fotoativo em relação ao sistema polimérico de HEC, aliado aos elevados rendimentos quânticos de formação de oxigênio singlete em relação aos demais compostos. Além disso, o encapsulamento influenciou significativamentente a interação e citolocalização dos fotossensibilizadores, e consequentemente a taxa e o mecanismo de morte celular. Os estudos por microscopia de fluorescência confocal, evidenciaram que as nanocápsulas de ACM são capazes de penetrar na membrana das células, alcançando o citoplasma e liberando gradativamente o composto fotoativo no seu interior. Quando não encapsulada, em solução de dmso, a porfirina se acumula preferencialmente na membrana celular. Consequentemente, neste caso a irradiação levou ao comprometimento da integridade da mesma e o desencadeamento da necrose celular, indesejável na terapia por ocasionar inflamação nos tecidos. Em contrapartida, o tratamento com formulações de fotossensibilizadores nanoencapsulados promoveram menos danos mas favoreceram a apoptose, um mecanismo de morte programada que geralmente leva a regeneração rápida e total dos tecidos, e ausência de processos inflamatórios<br>A series of eight monocationic porphyrins derivatives as free-base and Zn(II) complexes, with methyl or [Ru(bipy)2Cl]+ groups bond to the nitrogen atom of the meso-pyridyl substituent, were synthesized and characterized aiming their application as photosensitizers in the treatment of skin tumors by Photodynamic Therapy (PDT). Those compounds, especially the methylated derivatives of the free-base porphyrins, are potentially useful because showed higher quantum yields for the photoinduced formation of singlet oxygen and amphiphilic character, that enhanced their interaction with biological membranes. The low solubility in aqueous media, a limiting factor for use as photosensitizers, was overcome by encapsulating them in polymeric micro-and nanocapsules using the coacervation method. Two formulations, one based on hydroxyethyl cellulose (HEC) and another in the marine atelocollagen/xanthan gum (MAC) mixture were prepared and their photodynamic efficiencies and cytotoxicity against HeLa cells determined. The MAC formulations were shown to be non-toxic, while the HEC presented a small but significant cytotoxicity in the dark. On the other hand, all formulations become toxic when irradiated with 650 nm laser or white light from a mercury lamp source. The most actives, among all formulations, were those prepared using the methylated free-base porphyrin derivatives and MAC, probably due to the higher delivery efficiency of the photosensitizers in relation to the formulations prepared with HEC, associated with their higher quantum yields of photoinduced formation of singlet oxygen of those species as compared with the other compounds. In addition, the encapsulation influenced the interaction and cytolocalization of the photosensitizers, and consequently the rate and mechanism of cell death. The MAC nanocapsules were shown to penetrate the cell membrane by confocal fluorescence microscopy, reaching the cytoplasm where gradually released the photoactive compound. However, the porphyrin derivatives preferentially accumulated in the cell membrane when in DMSO solution. Consequently, the irradiation compromised the membrane integrity leading to necrosis, an undesirable process since cause tissue inflammation. In contrast, the treatment with encapsulated photosensitizer formulations promoted a much lower level of photoinduced damage and apoptosis, a more desirable death mechanism characterized by a complete and rapid regeneration of tissues and absence of inflammatory processes.

La présente thèse décrit la synthèse de briques de base de fullerènes pour la préparation de dispositifs moléculaires photoactifs combinant C60 et porphyrines. La cycloaddition alcyne-azoture catalysée au cuivre (I) a été utilisée comme outil de synthèse pour la préparation des dérivés C60 complexes.L’utilité synthétique de synthons C60 a été montrée avec la préparation d’édifices moléculaires complexes présentant des propriétés spécifiques pour diverses applications. Ainsi, un système photoactif flexible combinant C60 et porphyrine a été synthétisé. Cependant la flexibilité de l’espaceur liant les sous-unités de ce composé conduit à des variations de structurales importantes et complique ainsi l’analyse des études photophysiques.Dans ce contexte, nous nous sommes proposé dans une première partie de la présente thèse de parfaitement contrôler l’orientation et la distance des différentes sous-unités au sein de systèmes C60-donneurs. Afin de répondre à ce besoin, nous avons construit une brique de base de C60 rigide ayant un groupe azoture aromatique. Ainsi, la réaction « click » avec un phénylacétylène conjugué au groupement donneur conduit à un espaceur rigide entre les deux sous-unités.La deuxième partie de ce travail a été consacrée à la synthèse d’hexa-adduits du C60 portant différents groupements fonctionnels. Une méthode de synthèse permettant de préparer des hexa-adduits du C60 fonctionnalisés a été mise au point au laboratoire.Cette stratégie a été modifiée et des composés de C60 comportant dix fonctions azotures et une fonction alcyne protégée ont été synthétisés; dans ce cas il est possible d’introduire dans un premier temps par une réaction click dix groupes fonctionnels. Et dans un second temps; après déprotection de la fonction alcyne, une seconde réaction de click permet alors de greffer un fonctionnel différent<br>The present PhD thesis manuscript is focused on the use of fullerene building blocks for the preparation of photoactive molecular devices combining C60 and porphyrins. Cu(I) Catalyzed alkyne-azide cycloaddition was used as a synthetic tool for the preparation of complex C60 derivatives. Specifically, in the first part (Chapter II-B), a flexible fullerene-porphyrin triad has been developed and the photophysical studies were performed. The flexible linker between the fullerene core and the azide groups prevented any conformational control on the relative orientation and distance between the two photoactive subunits connected together. This prompted the development of an analogous building block in which the azide unit is directly connected to the bridging phenyl ring (Chapter II-C). In this way, the click reaction with porphyrin-alkyne derivatives give access to hybrid systems with a controlled relative orientation of the two moieties. This is of fundamental importance for a better understanding of the structural parameters affecting the electron and/or energy transfer kinetic in such dyads.In the second part (Chapter III), a fullerene hexaadduct scaffold is used to build up sophisticated multiporphyrin systems for various applications. The preparation of these multi-chromophoric ensembles relies on the click-click approach developed in our group

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico<br>A busca por processos quÃmicos que reduzam ou eliminem o uso e a geraÃÃo de substÃncias tÃxicas tem sido crescente nas Ãltimas dÃcadas. Com este novo direcionamento para reduÃÃo do impacto das atividades industriais, foram propostas alternativas que possam reduzir o impacto ambiental. Neste aspecto, foram sintetizados meso-porfirnas do tipo A4 (meso-5,10,15,20) a partir do LÃquido da Casca da Castanha do Caju - LCC (uma fonte renovÃvel, local, abundante e biodegradÃvel). O primeiro derivado refere-se à formaÃÃo do composto bromado, seguido da obtenÃÃo do derivado aldeÃdico, finalmente, com o auxÃlio do pirrol, tem-se a formaÃÃo da meso-porfirina. Os compostos foram purificados em coluna cromatogrÃfica e caracterizados por tÃcnicas experimentais de RMN 13C e 1H , GC-EM, IV e UV-VIS, que confirmaram a obtenÃÃo do produto desejado. A porfirina base livre foi submetida aos processos de metalaÃÃo utilizando-se para isto, Ni(C2H3O2).4H2O, Zn(CH3COO)2 e Cu(CH3COO)2, como sal doador do metal e diclorometano como solvente, a reaÃÃo permaneceu em agitaÃÃo constante. A metalaÃÃo foi acompanhada por espectroscopia no UV-VIS e cromatografia de camada delgada.<br>The search for chemical processes that reduce or el iminate the use and generation of toxic substances has been increasing in recent deca des. With this new direction for reducing the impact of industrial activities have p roposed alternatives that could reduce the environmental impact. Here, were synthesized po rphyrins of A4 type (5, 10,15,20) from the bark of the Net's Cashew nuts - LCC (a ren ewable source, location, abundant and biodegradable). The first derivative is the for mation of the compound bromine, followed by obtaining a secondary aldehydic, finall y, with the help of pyrrole, has been the formation of porphyrin. The compounds were puri fied by column chromatography and characterized by experimental techniques of 1 H and 13 C NMR, GC-EM, IR and UV- VIS, which confirmed the achievement of the desired product. The porphyrin free base was subjected to the processes of metallic using it for this, Ni(C 2 H 3 O 2 ).4H 2 O, Cd(CH 3 COO) 2 and Pb(CH 3 COO) 2 , as the metal salt donor and dichloromethane as solvent as the reaction methodology remained in con stant turmoil. The metallic processes were accompanied by the UV-VIS spectrosco py and thin-layer chromatography.

Processos que envolvem sensibilização são extremamente importantes para diversas áreas do conhecimento, incluindo a biologia, a química e a medicina. A aplicação de sensibilização em medicina tem se destacado, especialmente, em face de uma modalidade alternativa de tratamento de câncer denominada terapia fotodinâmica (TFD). Uma das linhas de pesquisas fundamentais para a evolução da terapia fotodinâmica é o desenvolvimento de novos fotossensibilizadores (Fs) com composição definida, que absorvam na janela terapêutica (600- 800nm) e que apresentem maior eficiência na indução de apoptose. Os Fs que apresentam cargas positivas e que são relativamente lipofílicos, permeiam membranas e são atraídos pelo potencial negativo das mitocôndrias, que tem papel central no controle da vida e da morte celular. Neste trabalho foi realizado um estudo da influência dos grupos funcionais na atividade dos Fs, através da funcionalização da protoporfirina IX (Pp IX). Foram estudadas três diferentes rotas sintéticas. Na rota I (esquema 14), utilizou-se como composto de partida a Hematoporfina IX (Hp IX), a qual foi funcionalizada com grupos aminas e amidas, respectivamente, nas hidroxilas e nas carboxilas. Esta rota forneceu baixo rendimento global (20%), e compostos de difícil purificação, no entanto obteve-se 1 composto puro. Na rota II (esquema 15), utilizou-se como composto de partida a Pp IX, a qual foi funcionalizada nos grupos vinílicos com grupos aminas. Obteve-se 4 compostos, com rendimento global de reação superior a 50%, mas observou-se que ocorre uma reação de eliminação que impede a quartenarização das aminas localizadas nas posições &#945; ao anel porfirínico. Na rota III (esquema 16), os grupos carboxílicos de Pp IX foram transformados em cloreto de ácido, que foram substituídos por compostos bifuncionais, amina primária e um segundo grupo. Esta rota possibilitou a obtenção de 7 compostos, inclusive compostos quaternários com rendimento global de reação superior a 70%. Dois derivados da clorofilina, que apresentam a banda QIV com um &#949; elevado em 650nm, foram também sintetizados. Todos os compostos, foram caracterizados estruturalmente de forma inequívoca através do espectro eletrônico (UV-vis e fluorescência), vibracional no infravermelho, RMN de 1H e 13C (1D e 2D) e espectrometria de massa. A série de compostos obtidos permitiu um estudo da relação entre a estrutura química do Fs com a sua fotoatividade. As propriedades fotofísicas foram caracterizadas por espectro de absorção e de emissão, fotólise de relâmpago a laser, eficiência quântica de fluorescência e de geração de oxigênio singlete. Estas determinações indicaram que as propriedades fotofísicas dos Fs não foram consideravelmente alteradas no processo sintético. Foi determinada a formação de agregados em solução aquosa e o equilíbrio monômero agregado foi deslocado no sentido da formação do monômero na presença de micelas de CTAB e SDS e de soro fetal. Observou-se, que a contribuição para desagregação é mais eficiente quando a carga da micela é oposta à do Fs. Foi determinado o coeficiente de partição octanol/água (logPo/a) em função do pH e constatou-se que os compostos que têm carga líquida apresentam valores de logPo/a entre -1 e 1 na faixa de pH entre 3 e 10. A incorporação destes compostos em lipossomos, seguiu perfil esperado considerando a carga, o logPo/a e a característica anfifílica dos compostos sintetizadas. Genericamente a eficiência de morte celular fotoinduzida seguiu o perfil de incorporação das drogas em células HeLa. Os estudos comparativos da citolocalização foram realizados por co-encubação das porfirinas sintetizadas com rodamina 123 (Rd), que se concentra em mitocôndrias. A localização em organelas citoplasmáticas foi determinada através de imagens obtidas por microscopia de fluorescência confocal. A sobreposição da emissão da Rd foi de 80% e 31% com o composto catiônico PpNpNI e aniônico PpNetPO3, respectivamente, comprovando a localização mitocondrial do composto positivo.<br>Processes that involve sensitization are extremely important for several areas of knowledge, including biology, chemistry and medicine. The application of sensitization in medicine is especially important, in face of an alternative modality of cancer treatment called Photodynamic Therapy (PDT). One of the lines of basic research important for the evolution of PDT is the development of new photosensitizers (PS) with defined composition, that absorb in the therapeutical window (600-800nm) and that present greater efficiency in the induction of apoptosis. Positively charged PS with the proper lipophilic/hidrophilic balance permeate membranes and are attracted by the negative potential of mitochondria, which is an organelle that has central roles in the control of cell life and death. In this work the influence of the functional groups in the activity of PS was carried out, through the functionalization of protoporphyrin IX (Pp IX). Three different synthetic routes were used. In route I (scheme 14), Hematoporphyrin IX (Hp IX), was used as departure compound and it was modified with amino and amide groups in hydroxyls and carboxyls, respectively. We found low yield in the synthetic (20%) and purification steps. However 1 pure PS was obtained. In route II (scheme 15), Pp IX was used as departure compound, which was modified in the vinilic groups with amino groups. We obtained 4 compounds, with global yield superior than 50%, but it was observed that an elimination reaction occurs that hinders the quarternization of the amino groups located in position &#945; to the porphyrin ring. Into route III (scheme 16), the carboxilic groups of Pp IX had been transformed into chloride acid, which was substituted by bi- functional groups, primary amine in one side and another group in the other. This route made it possible to obtain 7 compounds, including quaternary ammonium compounds with global yield superior than 70%. Two derivatives of chlorophyllin, that present QIV band with large extinction coefficient in 650nm, also were synthesized. All compounds were characterized structurally through the electronic and vibrational spectra (UV-vis and fluorescence, IR), RMN of 1H and 13C (1D and 2D) and mass spectrometry. This series of compounds allowed us to study the relation between the chemical structure of the Fs with its photoactivity. The photophysical properties were characterized by emission and absorption spectra, laser flash photolysis, fluorescence emission in the visible and NIR regions (generation of singlet oxygen). These determinations indicated that the photophysical properties of the PS were not modified in the synthetic process. The formation of aggregates were characterized in aqueous solution and the balance between aggregate and monomer species was dislocated in the direction of the formation of monomers in the presence of CTAB, SDS micelles and fetal serum. It was observed, that the disaggregating efficient is larger with micelles that have the opposite charges to that of the PS. The Octanol water partition coefficient (logPo/a), was determined as a function of pH. logPo/a values between -1 and 1 were observed for charged PS in the pH range of 3-10. The incorporation of these compounds in liposomes, followed the expected profile considering the charge, logPo/a and the amphifilic nature. Generically, the photoinduced cell death efficiency followed the profile of incorporation of the PS in HeLa cells. Comparative studies of cytolocalization were carried out by co-incubation of the cells with porphyrins and Rhodamine 123 (Rd), which localizes in mitochondria. The localization in cytoplasmic organelles was determined through fluorescence confocal microscopy images. The overlapping emission of the Rd was of 80% and 31% with the cationic PpNpNI and the anionic PpNetPO3 compounds, respectively, proving the mitochondrial localization of the positive PS.

Nesta tese serão discutidos alguns aspectos químicos, fotoquímicos e fotofísicos importantes no desenvolvimento de fotossensibilizadores para aplicação em terapia fotodinâmica (TFD). Os estudos abrangeram a investigação de 29 espécies, sendo que 20 delas continham um anel porfirínico convencional e 9 eram porfirinas duplamente N-confusas. As primeiras foram sintetizadas para apresentarem diferentes números e tipos de substituintes catiônicos coordenados à posição meso do anel porfirínico, mais especificamente as meso(N-4-piridil)fenilporfirinas e as meso(N-3-piridil)fenilporfirinas contendo um, dois (em trans), dois (em cis), três e quatro grupos [Ru(bipy)2Cl]+ ou CH3+ (figura 1). Em contraste com as porfirinas convencionais. as outras 9 estruturas consistiram das formas protonadas, neutras e desprotonadas de porfirinas que exibem dois anéis pirrólicos adjacentes voltados para fora do anel porfirínico, mais especificamente a base livre (H2N2CP) e os respectivos complexos de prata (AgHN2CP) e de cobre (CuHN2CP). Esta peculiaridade estrutural permite coordenar metais de transição por meio de dois átomos de carbono e dois de nitrogênio, estabilizando fortemente íons metálicos em estados de oxidação anormalmente elevados como Ag3+ e Cu3+. Os dois nitrogênios pirrólicos externos ao anel são susceptíveis tanto a protonação quanto a desprotonação, possibilitando a modulação das propriedades eletrônicas desses compostos por simples alteração no pH do meio. De um modo geral, a acidificação das amostras perturbou mais significativamente suas propriedades fotoquímicas que a desprotonação. Em especial, as espécies neutras metaladas apresentaram bandas bastante intensas na região fototerapêutica de 600 a 750 nm, além de um elevado rendimento quântico de formação de oxigênio singlete (&#934;&#916; &#62; 0,90 para o complexo Ag(III)). Todavia, um processo de fotodecomposição atribuído ao ataque do 1O2 formado, também foi observado. Ambos os processos, &#934;&#916; e fotodecomposição, parecem ser modulados pelo metal coordenado no centro do anel. Tanto a coordenação de Ag(lII) como Cu(lII) aumentou o &#934;&#916;, provavelmente devido ao efeito do metal pesado sobre o cruzamento interssistema. Todavia, verificou-se que o derivado AgHN2CP é muito menos reativo que o CuHN2CP e a base livre. Os motivos deste comportamento ainda não são completamente compreendidos, mas é evidente que o complexo de Ag(lII) apresenta melhores propriedades fotodinâmicas que as demais. Em comparação com as porfirinas duplamente N-confusas, as demais 20 porfirinas catiônicas são muito mais solúveis em água. Neste caso, o enfoque dos experimentos foi direcionado às aplicações biológicas propriamente ditas. Assim, além das propriedades fotofísicas associadas à formação de oxigênio singlete (1O2), também foram exploradas a influência do número dos substituintes periféricos sobre a ligação e danos fotooxidativos provocados em eritrócitos, lipossomos, mitocôndrias e células cancerígenas. Os resultados de &#934;&#916; mostraram ser inversamente proporcionais ao número de cargas positivas, para as porfirínas contendo grupos N-4metilpiridíniom. Estas diferenças foram consistentes com os efeitos de agregação, causados pela formação de dímeros ou oligômeros, no caso das espécies mais hidrofóbicas. Os coeficientes de partição em n-octanol/água (logPOA) corroboraram estes resultados, apresentando uma dependência inversamente proporcional ao número de cargas positivas ou proporcional ao número de resíduos fenila. As eficiências de ligação à bicamada lipídica mitocondrial, lipossomal e celular e os processos de peroxidação lipídica fotoinduzidos mostraram uma dependência proporcional aos valores de logPOA, exceto para as porfirinas contendo complexos de rutênio. O comportamento não linear neste último caso pode estar associada a dissociação da ligação rutênio-porfirina, devido a elevada força iônica das soluções fisiológicas utilizadas. Neste caso, a descoordenação dos complexos periféricos deve promover uma drástica diminuição da solubilidade do composto. Por este motivo os experimentos foram conduzidos somente com as espécies metiladas. No caso, de mitocôndrias isoladas verificou-se que a interação também apresenta uma razoável participação do potencial de membrana. De fato, quando a mitocôodria estava energizada foi observado um acréscimo de 15% no acúmulo da 3P2cMe em comparação com à mitocôndria desacoplada. Para as demais porfirinas houve um menor acúmulo com o aumento do número de resíduos N-3-metilpirídínio. Em todos os experimentos, um comportamento diferenciado foi observado no caso dos isômeros dicatiônicos. A espécie com cargas dispostas nas posições cis (3P2cMe) apresentou praticamente o dobro de eficiência que o correspondente isômero trans (3P2tMe). Este comportamento parece consistente com uma maior penetração da primeira espécie na bicamada lipídica, proporcionado pelo caráter antipático de sua estrutura química. Os resultados apresentados neste estudo mostraram que estas séries de meso-porfirinas catiônicas constituem sistemas bastante interessantes para a compreensão dos efeitos estruturais envolvidos na ação fotodinâmica dos compostos sobre membranas lipídicas, devido à possibilidade de modulação da relação hidrofilicidade/lipofilicidade, sem alterar significativamente a eficiência na formação de 1O2. Além disso, a disposição espacial das cargas positivas na estrutura do fotossensibilizador demonstrou ser extremamente crítica no processo de ancoragem do mesmo na membrana celular ou mitocondrial e consequentemente em causar efeitos fotooxidativos mais eficientemente. As porfirinas contendo grupos 3-metilpiridínio apresentam vantagens sobre as 4-metilpiridínio, normalmente estudas, por serem mais hidrofílicas, terem menor tendência de agregação e possuírem similar atividade fotodinâmica. Em especial, a estrutura anfipática da 3P2cMe associada a sua elevada formação de 1O2 e estabilidade lhe conferem uma interessante potencialidade como agente fototerapêutico.<br>In this thesis the chemical, photochemical and photophysical relevant aspects for the development of new photosensitizers for photodynamic therapy applications are discussed. 20 conventional porphyrins species and 9 doubly Nconfused porphyrins species were investigated. The first series contains variable number (1 to 4) of cationic groups, [Ru(bipy)2CI]+ or CH3+ (figure 1), bound to the meta or para-pyridil N-atoms of meso-phenylpyridylporphyrins. On the other hand, the protonated, neutral and deprotonated doubly N-confused porphyrins possess two rotated adjacent pyrrol rings, such that they have two coordinating camon atoms. Consequently, transition metal ions in unusually high oxidation states such as Ag(lII) and Cu(lII) can be stabilized by this structure, while the outer pyrrol N-atoms are susceptible to protonation and deprotonation reactions, allowing the modulation of their electronic properties simply by controlling the pH of the solution. In general, the protonation perturbed more significantly the photochemical properties than the deprotonation. The neutral species exhibit intense absorption bands in the phototherapeutical range (600 to 750 nm), associated with a high singlet oxygen sensitization quantum yield (&#934;&#916;&#62; 0,90 for the Ag(lII) complex). Furthermore, a photodecomposition process due to the reaction with 1O2 was also identified. Both &#934;&#916; and photodecomposition are influenced by the metal ion coordinated to the doubly N-confused porphyrin ring. The coordination of Ag(lIl) and Cu(lII) increased &#934;&#916;, probably due to the enhancement of intersystem crossing quantum yield associated with the heavy atom effects. However, AgHN2CP is much more stable than CuHN2CP or the free-base, but the reasons are not clear and should be further investigated. The above results clearly evidence the superior properties of the Ag(lIl) complex as photosensitizer for PDT applications. The 20 cationic pyridylporphyrin derivatives are much soluble in water and experiments directed to biological applications could be carried out. Accordingly, in addition to the quantum yield for singlet oxygen generation(1O2), the effect of the stereochemistry and number and position of the electrically charged substituents on the binding constants and photooxidative damage on erythrocytes, lipossomes, mitochondria and HeLa cells were evaluated. The &#934;&#916; values were constant in the case of the N-3-methylpyridinium derivatives but inversely proportional to the number of positive charges for the N-4-methylpyridinium derivatives. This was assigned to an increase of aggregation of the sensitizers as the number of meso-phenyl rings and the lipophylicity increase. The partition coefficients in n-octanol/water (logPOA) corroborate that assertion showing a linear correlation with increasing of the number of phenyl groups. The binding efficiency towards the mitochondrial, lipossomal and cellular membrane and the photo-induced lipidic peroxidation processes were directly proportional to the logPOA, except for the ruthenated porphyrins. This last behavior may be associated with the dissociation reactions of the rutheniumpyridylporphyrin bond in the physiologic solution. Accordingly, those experiments were carried out only with the methylpyridynium derivatives. For the first time, we showed inequivocally that the interaction of the methyllated porphyrins with mitochondria are significantly influenced by the membrane potential. In fact, when the mitochondria was energized a 15% increase was observed in the binding constants of 3P2cMe in comparison with teh results with decoupled mitochondria. Also, the amount of bond porphyrin sensitizer decreased as the number of methylpyridynium groups was increased, following the same tendency as above. The behavior of the cis (3P2cMe) and trans (3P2tMe) isomers didn\'t follow the general tendency for the other derivatives in a series, such that the binding constants of the cis isomers were always about twice higher than for the trans, which were much higher than predicted by the general behavior. This means that they can associate more strongly and penetrate deeper in the membrane than the more charged porphyrin derivatives. In particular, the cis species is amphiphilic, i.e. possess an adequate structure for that interaction. The results presented in this thesis showed conclusively that the two series of meso-phenylpyridylporphyrins are adequate for the investigation of the effect of the stereochemistry on the bonding ability and photodynamic properties of those photosensitizers. This is particularly true due to the possibility of modulating the ratio between hydrophobicitylhydrophylicity and the stereochemistry without influencing significantly the quantum yield for 1O2 generation. The meta- series showed an advantage over the conventionally used para- series of methylpyridynium porphyrins because it is more soluble and shows lesser tendency to aggregate. In condusion, the amphiphilic 3P2cMe is the species with the highest potentiallity as por sensitizer because of its high binding constants, low tendency to associate and high &#934;&#916;.

Made available in DSpace on 2017-07-24T19:38:03Z (GMT). No. of bitstreams: 1 Elementos pre textuais.pdf: 126219 bytes, checksum: a4c1ca3bb1afd43046bbfa4177592e32 (MD5) Previous issue date: 2010-02-26<br>There is a considerable interest in the synthesis of water soluble porphyrins due to its use as models of biological systems, as drugs and as homogeneous catalysts in aqueous media. Within this context, this work describes the synthesis of meso-tetraphenylporphyrins with reactive groups on the meso-phenyl ring to generate trimethylarylammonium salts derivatives, resulting in cationic porphyrins with hydrophilic character. Thus, it was obtained iodide salts of 4-TMA-TPP 13 by the complete alkylation of 4-DMA-TPP 15 (91% yield), and 4-NH2-TPP 12 using 2,6-lutidine (69% yield). The synthesis of porphyrins 2-NO2-TPP 16, 2-NH2-TPP 17, 4-NO2-TPP 14, 4-NH2-TPP 12 and 4-DMA-TPP 15 were also studied. The methods described in the literature for the synthesis of 2-NO2-TPP 16 and 4-NO2-TPP 14 were optimized, and the yield (40%) of for 2-NO2-TPP 16 was higher than those reported in the literature (5% overall yield). Porphyrins 17 and 12 were obtained by reduction of 16 and 14, respectively, using concentrated hydrochloric acid and tin (II) chloride dihydrate, without requiring an inert atmosphere. The method was improved, thus facilitating the isolation and purification steps. The synthesis of 4-DMA-TPP 15 was performed using both Adler-Longo method (5% yield) and a modification of Adler’s method, using 1:1 mixture of propionic and octanoic acids (7,0% yield). The porphyrins were fully characterized by infrared, UV-Vis and RMN spectroscopies. All the spectral data were consistent with those reported in the literature.<br>Há considerável interesse na síntese de porfirinas aquossolúveis devido à possibilidade de usá-las como modelos de sistemas biológicos, como drogas e como catalisadores homogêneos em meio aquoso. Dentro deste contexto, este trabalho descreve a síntese de meso-tetrafenilporfirinas com substituintes reativos no anel meso-fenila para obtenção de derivado porfirínico catiônico, resultando em porfirinas com caráter hidrofílico. Assim, obtivemos sais de iodeto de 4-TMA-TPP 13 a partir da metilação de 4-DMA-TPP 15, com rendimento de 91%, e a partir da metilação de 4-NH2-TPP 12, usando 2,6-lutidina, com rendimento de 69%. A reação de obtenção das porfirinas 2-NO2-TPP 16, 2-NH2-TPP 17, 4-NO2-TPP 14, 4-NH2-TPP 12 e 4-DMA-TPP 15 também foram estudadas. Os métodos descritos na literatura para a síntese da 2-NO2-TPP 16 e 4-NO2-TPP 14 foram alterados para facilitar e otimizar as etapas de isolamento e purificação. Para a 2-NO2-TPP 16 obteve-se rendimento de 40%, superior aos 5% descritos em literatura. As amino-porfirinas 17 e 12 foram obtidas por redução de 14 e 16, respectivamente, utilizando-se ácido clorídrico concentrado e cloreto de estanho (II) dihidratado e, sem a necessidade de atmosfera inerte. O método foi assim simplificado, facilitando as etapas de isolamento e purificação. A síntese da 4-DMA-TPP 15 foi a partir do método Adler-Longo, com rendimento de 5,0%, e a partir do método de Adler-Longo modificado em que utilizou-se como solvente uma mistura 1:1 de ácido propanóico e octanóico, com rendimento de 7,0%. As porfirinas sintetizadas foram caracterizadas por espectrometria na região do infravermelho (IV), do ultravioleta e visível (UV-Vis) e por ressonância magnética nuclear (RMN) de H1 e C13. Os dados espectrais obtidos estão de acordo com os descritos na literatura.

Anthraquinone (AQ) derivatives with relatively high reduction potentials have been synthesized to afford good candidates for electron transfer studies in DNA. Electron withdrawing groups on the anthraquinone ring gave derivatives with less negative reduction potentials. The anthraquinone imide (AQI) derivatives had reduction potentials less negative than AQ derivatives. The AQI ring system was subject to base-induced hydrolysis. Water-soluble sulfonated tetraarylporphyrins have been studied in a wide variety of contexts. Herein, we report the first synthesis of a pentasulfonated porphyrin bearing an internal cyclic sulfone ring. Treatment of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS4) with fuming H2SO4 gave a structure consistent with initial sulfonation followed by dehydration to give a sulfone bridge between an ortho-position of one of the phenyl groups and a β-pyrrole position on the porphine ring (TPPS4Sc). The structure was established by ESI-MS and 1HNMR. The Soret absorption is red shifted by about 32 nm compared to that of TPPS4. Streptococcus pyogenes obtains iron by taking up heme from the environment during infection. One of the heme uptake pathways is the Sia or Hts pathway. The initial protein in this pathway is Shr, which has two heme-binding NEAT domains, NEAT1 nearer the N-terminus, and NEAT2 nearer the C-terminus. We report biophysical characteristics of these two NEAT domains. To assess stability of this domain towards heme release, denaturation studies of the Fe(II) and Fe(III) forms were performed. For each domain, both the Fe(II) and the Fe(III) forms behave similarly in thermal denaturation and guanidinium denaturation. Overall, NEAT2 is more stable than NEAT1. Spectral signatures, sequence alignment and homology modeling for both domains suggest that one of the axial ligands is methionine. NEAT2 autoreduces as the pH increases and autooxidizes as the pH decreases. Heme uptake from the host environment is the only iron acquisition pathway in S. pyogenes; inhibition of this pathway might be an approach to infection control. Compounds that might inhibit the heme uptake pathway were selected via virtual screening.

En aquest treball s’ha desenvolupat la química dels 2,2’-bipirroles. En aquest sentit, s’ha obtingut el derivat 5,5’-dibromo-2,2’-bipirrole per un tractament del 2,2’-bipirrole amb N-bromosuccinimida. La aplicació de reaccions de química organometálica, com les reaccions de Suzuki o Stille, ha permès l’ obtenció d’oligòmers del 2,2’-bipirrole, els quals presenten propietats òptiques per la seva aplicació en optoelectrònica. La química del pal·ladi aplicada al 5,5’-dibromo-2,2’-bipirrole ha permès l’obtenció del primer quaterpirrole estable per a síntesis de macrocicles, entre els que es destaquen les porfirines esteses com la hexafirina, la heptafirina, la octafirina y també els ciclo[8]pirroles. Seguint el mateix esquema també s’ha obtingut el primer sexipirrole estable per a síntesis de macrocicles. El sexipirrole s’ha obtingut mitjançant la reacció de Suzuki de un quaterpirrole dibromat estable a temperatura ambient amb un derivat borònic del pirrole. Aquest producte ha permès la obtenció de les primers porfirines esteses que contenen el sexipirrol a la seva estructura macrocíclica, aconseguint macrocicles de 10 y 12 unitats de pirrole. Amb la química desenvolupada per a l’obtenció de oligòmers y macrocicles derivats del pirrole, s’han pogut obtenir diversos polímers conjugats amb reaccions d’ acoblament organometàl·lic del 5,5’-dibromo-2,2’-bipirrole, o mitjançant una polimerització oxidant o electroquímica d’ oligòmers del 2,2’-bipirrole. S’ha observat que els polímers presenten selectivitat en front del anió fluorur, observant-se un canvi de color y una disminució en la fluorescència.<br>En el presente trabajo se ha desarrollado la química de los 2,2’-bipirroles. Para ello se ha obtenido el derivado 5,5’-dibromo-2,2’-bipirrol mediante el tratamiento del 2,2’-bipirrol con N-bromosuccinimida. La aplicación de reacciones de química organometálica como Suzuki y Stille ha permitido la obtención de diversos oligómeros del 2,2’-bipirrol, los cuales presentan propiedades ópticas para su aplicación en optoelectrónica. La química del paladio aplicada al 5,5’-dibromo-2,2’-bipirrol ha permitido la obtención del primer cuaterpirrol estable para síntesis de macrociclos, entre los que cabe destacar las porfirinas expandidas tales como la hexafirina, heptafirina u octafirina, y también los ciclo[8]pirroles. Con el mismo esquema se ha obtenido también el primer sexipirrol estable para síntesis de macrociclos. El sexipirrol se ha obtenido mediante la reacción de Suzuki de un cuaterpirrol dibromado, estable a temperatura ambiente, con un derivado borónico del pirrol. Éste producto ha permitido la obtención de las primeras porfirinas expandidas que contienen el sexipirrol en su estructura macrocíclica, consiguiendo macrociclos de 10 y 12 unidades de pirrol. La química desarrollada para la obtención de oligómeros y macrociclos del pirrol ha permitido también la obtención de diversos polímeros conjugados a partir de reacciones de acoplamiento organometálico del 5,5’-dibromo-2,2’-bipirrol, o mediante una polimerización oxidante o electroquímica de oligómeros del 2,2’-bipirrol. Se ha observado que los polímeros presentan selectividad frente al anión fluoruro, observándose un cambio de color y un decaimiento en la fluorescencia.<br>In this work, the chemistry of a new family of 2,2’-bipyrroles has been developed. For this purpose a 5,5’-dibrominated-2,2’-bipyrrole has been prepared by treating 2,2’-bipyrrole with N-bromosuccinimide. The use of organometallic reactions such as Suzuki or Stille has allowed to achieve a new family of 2,2’-bipyrrole oligomers with interesting optical properties for optoelectronics. This methodology has allowed the preparation of the first stable quaterpyrrole. This new compound have given access to the synthesis of new macrocycles, including expanded porphyrins such as hexaphyrins, heptaphyrins, octaphyrins or cyclo[8]pyrroles. The first stable sexipyrrole for macrocycle synthesis has been obtained. Sexipyrrole has been prepared using the Suzuki reaction of a dibrominated quaterpyrrole with a pyrrole boronic derivative. This sexipyrrole has allowed the preparation of the first expanded porphyrins using sexipyrrole as a starting material. The synthesis of decaphyrin and dodecaphyrin has been achieved. The same chemistry developed for the preparation of oligomers and macrocycles has allowed the preparation of several 2,2’-bipyrrole conjugated polymers by means of organometallic coupling of 5,5’-dibrominated-2,2’-bipyrrole, or with oxidant or electrochemical polymerization of 2,2’-bipyrrole oligomers. It has been observed that some of these polymers acts as fluoride sensors.

Made available in DSpace on 2017-07-24T19:37:52Z (GMT). No. of bitstreams: 1 Ariana Rodrigues.pdf: 4102019 bytes, checksum: 823cb458ebe2eea53b3ba0d11aed9880 (MD5) Previous issue date: 2012-03-06<br>Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Paraná<br>The increasing pathogenic bacteria resistance to antibiotics has led to the development of new alternatives to replace them. The Photodynamic Antimicrobial Chemotherapy (PACT) is one of the alternatives recently researched. Several associations between photosensitizer (PS) and light sources are used to inactivate different micro-organisms. The porphyrin derivatives have interesting features and are amongst the most investigated compounds in PACT, showing promising results. The light-emitting diode (LED) source presents advantages, since this device has been shown efficient against bacteria and is economically feasible. The present study investigated the photodynamic activity of different porphyrin derivatives/LED systems for application in PACT. The following porphyrin derivatives were used: 5,10,15,20-tetrakis(2,6-difluor-5-sulfonatophenyl) sodium porphyrinate, Na4[H2(TDFSPP)], 5,10,15,20-tetrakis(2,6-difluor-5-sulfonatophenyl) zinc (II) sodium porphyrinate, Na4[Zn(TDFSPP)]) and 5,10,15,20-tetrakis(4-sulfonatophenyl) manganese (III) sodium porphyrinate, Na4[Mn(TSPP)]. LED systems were used in different emission bands: orange, red, green and blue. The photodynamic activity of PS/LED systems were analyzed through the photobleaching test, photoxidation of bovine serum albumin (BSA) protein, uric acid and microbiological assay with ATCC and hospital Staphylococcus aureus strains. The results showed no significant photobleaching of porphyrin derivatives using LED as a light source. The PS/LED systems led to oxidation of the BSA protein and uric acid, except for the derivative Na4[Mn(TSPP)]. The photoxidation constant rate for Na4[H2(TDFSPP)]/green and blue LED, Na4[Zn(TDFSPP)]/green and blue LED systems, were close to the constant rate for drugs with application in photodynamic therapy (PDT). The uric acid test result indicated that compounds are capable of generating singlet oxygen. The Na4[H2(TDFSPP)]/blue LED system had a higher photodynamic activity against ATCC and hospital S. aureus strains. The results demonstrated that the systems under study present potential to be used in PDT and PACT.<br>A crescente resistência de bactérias patogênicas a antibióticos levou ao desenvolvimento de novas alternativas que possam substituí-los. Uma das alternativas investigadas atualmente é a quimioterapia fotodinâmica antimicrobiana (PACT). Várias associações entre fotossensibilizadores (FS) e fontes de luz são utilizadas para inativar diferentes micro-organismos, comprovando a eficiência dessa terapia. Os derivados porfirínicos apresentam características interessantes para aplicação em PACT e estão entre os compostos mais investigados, apresentando resultados promissores. O uso de LED como fonte de luz apresenta vantagens, uma vez que esse dispositivo tem mostrado bons resultados na eliminação de bactérias e é economicamente mais viável. Assim, no presente estudo, investigou-se a atividade fotodinâmica de diferentes sistemas derivados porfirínicos/LEDs para possível aplicação em PACT. Para isso, utilizou-se os seguintes derivados porfirínicos: 5,10,15,20-tetrakis (2,6-difluoro-5-sulfonatofenil) porfirinato de sódio, Na4[H2(TDFSPP)], 5,10,15,20-tetrakis (2,6-difluoro-5-sulfonatofenil) zinco (II) porfirinato de sódio, Na4[Zn(TDFSPP)], e 5,10,15,20-tetrakis (4-sulfonatofenil) manganês (III) porfirinato de sódio, Na4[Mn(TSPP)]. A irradiação dos compostos foi feita utilizando-se sistemas de LED com diferentes faixas de emissão: alaranjado, vermelho, verde e azul. A atividade fotodinâmica dos sistemas FS/LED foi avaliada por meio dos testes de fotobranqueamento, foto-oxidação da proteína BSA, ácido úrico e de ensaio microbiológico, utilizando-se a bactéria Staphylococcus aureus de origem ATCC e hospitalar. Os resultados mostraram que os derivados porfirínicos não sofreram fotobranqueamento quando associados aos diferentes LEDs. Os sistemas FS/LED levaram à oxidação da proteína BSA e à degradação da molécula de ácido úrico, exceto para o derivado Na4[Mn(TSPP)]. As constantes de foto-oxidação obtidas para os sistemas Na4[H2(TDFSPP)]/LED verde e azul; Na4[Zn(TDFSPP)]/LED verde e azul, ficaram próximas aos valores obtidos para fármacos com aplicação em Terapia Fotodinâmica (TFD). Os resultados do teste do ácido úrico para esses mesmos sistemas indicaram que eles são capazes de gerar oxigênio singlete. O sistema Na4[H2(TDFSPP)]/LED azul apresentou maior atividade fotodinâmica sobre as cepas de S. aureus ATCC e hospitalar. Assim, os resultados demonstram que os sistemas investigados apresentam potencial para aplicação em TFD e PACT.

Le biocartol ou acide (1r)-cis-hemicaronaldehydique, un compose cyclopropanique enantiopur provenant de la synthese industrielle d'insecticides pyrethroides, est utilise comme synthon pour la preparation de nouvelles porphyrines chirales. Nous decrivons la synthese d'amides du biocartol, puis la synthese des porphyrines correspondantes par condensation avec le pyrrole. Celles-ci sont obtenues exclusivement sous la forme de l'atropoisomere , avec un rendement variant de 7 a 60%. Une serie de complexes de manganese (iii) de ces chiroporphyrines, derivees d'amides et d'esters du biocartol, ont ete prepares. Ces complexes sont de bons catalyseurs pour l'epoxydation asymetrique d'olefines prochirales. Les substrats a structure rigide cyclique sont epoxydes avec la plus grande selectivite. Ainsi, des exces enantiometriques allant jusqu'a 86% ont ete obtenus pour l'epoxydation du 1,2-dihydronaphtalene en (1s, 2r)-epoxy-1,2,3,4-tetrahydronaphtalene. L'influence de differents facteurs (nature des substituants, solvant, ligand axial, metal) sur la reactivite et l'enantioselectivite ont ete etudies. Des etudes structurales par resonance magnetique nucleaire et par diffraction des rayons x ont permis d'etablir une correlation entre structure et induction asymetrique dans cette serie. Nous avons mis en evidence que l'encombrement sterique au niveau du centre metallique lors de l'epoxydation est le determinant principal de l'enantioselectivite. Ces resultats sont interpretes par un modele geometrique de l'approche de l'olefine vers le centre metallique. La complexation d'amines derivees d'olefines prochirales par les chiroporphyrines de cobalt (iii) a egalement ete etudiee.

Des complexes metalliques de la tetramethylchiroporphyrine, de symetrie et possedant des groupements meso derives du biocartol, ont ete synthetises, caracterises, et utilises dans quatre axes de recherches. _la caracterisation du complexe bis-ethanol de la tetramethylchiroporphyrine de fer(iii), en solution et en phase solide, revele que ce compose presente un etat de spin inhabituel : le spin intermediaire pur (s = 3/2). _l'insertion d'un metal diamagnetique, le cobalt(iii), coordonnant les amines au cur de la porphyrine, a permis l'analyse qualitative et quantitative de la composition de derives d'amines par resonance magnetique nucleaire du proton. Cette methode s'est averee precise, fiable, rapide et tres facile d'utilisation. _l'addition de -aminoalcools sur cette meme molecule resulte en la complexation preferentielle d'un enantiomere. Les aspects cinetiques et thermodynamiques ont ete abordes, et une explication quant a l'enantioselectivite observee est avancee sur la base de liaisons hydrogene intramoleculaires de type c-h___o. _parmi differentes complexes de la tetramethylchiroporphyrine, ceux de fer(iii) et de manganese(iii) ont donne les meilleurs resultats pour la catalyse d'aziridination asymetrique, avec des exces enantiomeriques allant jusqu'a 57% pour le styrene. Un point remarquable est l'induction asymetrique opposee de ces deux catalyseurs, chacun favorisant la formation majoritaire d'un enantiomere.

Tese arquivada ao abrigo da Portaria nº 227/2017 de 25 de Julho.<br>The thesis consists of two major research topic i.e. Porphyrin and Nano crystalline cellulose. The porphyrin project started with the production of porphyrin chromophores for dye sensitized solar cells. These derivatives were required as references for an ongoing project of the research group that hosted me. In addition, some porphyrin-porphyrin tweezers were prepared using a one pot synthetic methodology developed in our lab, based on the use of trichloro triazine as a linker. These derivatives were necessary for collaboration with Professor Nina Berova at Columbia University that studies their use for the determination of the absolute configuration of chiral molecules by circular dichroism. After this training period, the thesis project continued with an original research based on the use of clickchemistry for porphyrin functionalization. The nanocellulose project started with the production of nanocrystalline cellulose from microcrystalline cellulose by acid hydrolysis. The nanocellulose has chemically modifiable OH groups on the surface. This allows the use of a wide range of chemical reactions for its functionalization. The linking of a pH sensitive dye on the surface of NCC was studied. In addition, several strategies were being employed for the functionalization of NCC with other groups such as cationic substituents (using (2,3-epoxypropyl)trimethylammonium chloride), amino (using epichlorohydrin and 3-aminopropyltrimethoxysilane), carboxy (using ammonium persulfate and TEMPO). Out of various chemical modifications carried out on NCC, the TEMPO mediated carboxylation for introduction of carboxyl group on NCC was proved to be easy, convenient and even resulted in high degree of functionalization. Using these material and typical carbodiimide chemistry, functional groups such as porphyrins (that acts as a sensitizer for singlet oxygen production) and a nitro-derivative (capable of producing NO upon irradiation) were prepared. These features are under study to verify their potential in various therapeutic applications.

Thesis (M.Sc.)--York University, 2003. Graduate Programme in Chemistry.<br>Typescript. Includes bibliographical references (leaves 88-91). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pMQ99270

by Ka Lok Cheng.<br>Thesis (M.Phil.)--Chinese University of Hong Kong, 2000.<br>Includes bibliographical references (leaves 115-122).<br>Abstracts in English and Chinese.<br>Abstract --- p.i<br>Abstract (in Chinese) --- p.ii<br>Acknowledgement --- p.iii<br>Table of Contents --- p.iv<br>List of Figures --- p.viii<br>List of Tables --- p.xi<br>Abbreviations --- p.xii<br>Chapter PART I --- SYNTHESIS OF FERROCENE-CONTAINING PUSH-PULL DIPHENYLPORPHYRINS --- p.1<br>Chapter Chapter 1 --- Introduction --- p.2<br>Chapter 1.1 --- Introduction to Nonlinear Optics --- p.2<br>Chapter 1.1.1 --- Interactions of Light with Matters --- p.2<br>Chapter 1.1.2 --- Structural Requirements of Second-Harmonic Generating Molecules --- p.4<br>Chapter 1.2 --- Ferrocene as an Electron Donor in Second Harmonic Generating Molecules --- p.7<br>Chapter 1.3 --- Porphyrin as a Platform of Second Harmonic Generating Molecules --- p.16<br>Chapter 1.4 --- Target Molecules of this Project --- p.22<br>Chapter Chapter 2 --- Result and Discussion --- p.23<br>Chapter 2.1 --- Preparation of Alkynyl Fragments --- p.23<br>Chapter 2.1.1 --- Preparation of 2-ferrocenylethyne (24) --- p.23<br>Chapter 2.1.2 --- Preparation of 1 -ethynyl-4-nitrobenzene (26) --- p.24<br>Chapter 2.1.3 --- "Preparation of l-ethynyl-4-(N,N-dimethylaminophenyl) benzene (28)" --- p.25<br>Chapter 2.2 --- Preparation of Porphyrin Precursors --- p.26<br>Chapter 2.3 --- "Synthesis and Characterizations of 5-(2'-Ferrocenylethynyl)-l5- formyl-10,20-diphenylporphyrinatonickel(II) (36)" --- p.29<br>Chapter 2.4 --- "Synthesis and Characterizations of 5-(2',2'-Dicyanoethenyl)-l5- (2""-Ferrocenylethynyl)-10,20-diphenylporphyrinatonickel(II) (38)" --- p.33<br>Chapter 2.5 --- "Synthesis and Characterizations of 5-Ferrocenylethynyl-l 5-(4""- nitrophenylethynyl)-10,20-diphenylporphyrinatonickel(II) (40)" --- p.37<br>Chapter 2.6 --- "Synthesis and Characterizations of 5-Ferrocenylethynyl-l 5-(4'- (N,N-dimethylamino)phenyl)ethynyl)-10,20-diphenyl porphyrinatonickel(II) (47)" --- p.43<br>Chapter 2.7 --- Conclusion for Part One --- p.47<br>Chapter Chapter 3 --- Experimental Section --- p.48<br>Chapter 3.1 --- General Information --- p.48<br>Chapter 3.2 --- Physical Measurements --- p.48<br>Chapter 3.3 --- Preparation of Alkynyl Fragments --- p.49<br>Chapter 3.4 --- Preparation of Some Known Porphyrins --- p.54<br>Chapter 3.5 --- "Synthesis of Ferrocenyl ""Push-pull"" Porphyrin" --- p.58<br>Chapter PART II --- LIGHT-HARVESTING NAPHTHALENE-PHTHALOCYANINE SYSTEMS --- p.65<br>Chapter Chapter 4 --- Introduction --- p.55<br>Chapter 4.1 --- Porphyrin-based Light-harvesting systems --- p.66<br>Chapter 4.1.1 --- Multiporphyrins --- p.57<br>Chapter 4.1.2 --- Carotenoid-porphyrins --- p.74<br>Chapter 4.1.3 --- Boron-dipyrrin porphyrins --- p.75<br>Chapter 4.1.4 --- Anthracene-porphyrin systems --- p.73<br>Chapter 4.1.5 --- Dendritic porphyrins --- p.79<br>Chapter 4.2 --- Phthalocyanine-based Light-harvesting systems --- p.80<br>Chapter 4.3 --- Objective of this project --- p.83<br>Chapter Chapter 5 --- Result and Discussion --- p.84<br>Chapter 5.1 --- Preparation of naphthalene-phthalocyanine systems --- p.84<br>Chapter 5.1.1 --- Synthesis of zinc(II) tetra( 1 -naphthoxy)phthalocyanines --- p.84<br>Chapter 5.1.2 --- Synthesis of tetra[2-(l´ة-naphthoxy)ethoxy] phthalocyaninatozinc(II) (83) --- p.85<br>Chapter 5.1.3 --- "Synthesis of 2,3,9,10,16,17,23,24-octa( 1 -naphthoxy) phthalocyaninatozinc(II) (89)" --- p.86<br>Chapter 5.2 --- Absorption spectra of naphthalene-phthalocyanine systems --- p.88<br>Chapter 5.2.1 --- Absorption spectra at different concentrations --- p.89<br>Chapter 5.2.2 --- Comparison of the absorption spectra of the naphthoxy phthalocyanine with the spectra of the mixture of corresponding 1-ethoxynaphthalene and alkoxyphthalocyanines --- p.92<br>Chapter 5.3 --- Fluorescence Quantum yields of Naphthalene-Phthalocyanine Systems --- p.96<br>Chapter 5.4 --- Singlet-singlet energy transfer efficiencies of Naphthalene- phthalocyanine Systems --- p.98<br>Chapter 5.4.1 --- Methodology --- p.98<br>Chapter 5.4.2 --- Determination of energy transfer quantum yields --- p.99<br>Chapter 5.5 --- Conclusion for Part II --- p.103<br>Chapter Chapter 6 --- Experimental Section --- p.104<br>Chapter 6.1 --- General Information --- p.104<br>Chapter 6.2 --- Synthesis of tetra( 1 -naphthoxy)phthalocyanines --- p.105<br>Chapter 6.3 --- Synthesis of tetra(naphthoxyethoxy)phthalocyanine --- p.108<br>Chapter 6.4 --- Synthesis of octa( 1 -naphthoxy)phthalocyanine --- p.111<br>References --- p.115<br>Appendix A: Spectra of new compounds not discussed in the main text --- p.123<br>Appendix B: X-ray crystallographic data of compound40 --- p.133

碩士<br>國立成功大學<br>光電科學與工程學系<br>101<br>This study aims to employ synthetic porphyrins in organic planar heterojunction (PHJ) solar cells. The results suggest a well-defined Donor / Acceptor interface between porphyin and fullerene derivatives, which exhibit credible photovoltaic efficiency. Also, the improved open-circuit voltage (VOC) and device performance are observed through alternating acceptor components in the active layer. Comparative studies of thin-film properties and device characteristics are reported, in which the same porphyrin material is deposited using both solution-process and thermal deposition in vacuum. In addition, a series of porphyrin derivatives is investigated as electron donor in porphyrin-base organic solar cells to get more insights into the correlations between molecular structures and device characteristics.

The thesis is in three parts. Initially, work centred on the development of conjugation technology for covalently binding the photosensitizer (PS) benzoporphyrin derivative monoacid ring A (BPD) to monoclonal antibodies (MoAbs) using a water soluble carrier molecule, modified poiyvinyi alcohol (M-PVA). This conjugation procedure has been shown to be reliable and reproducible and result in negligible loss of biological activity of both MoAb and PS. The second part of the thesis was focused on determining the specificity and selectivity of the MoAb-PS conjugate in an In vitro system. The 5E8 MoAb, specific for human squamous cell lung cancer (A549), was used in this study. Extensive studies in which the 5E8-M-PVA-BPD conjugate was tested and compared with an irrelevant control conjugate - T48-M-PVA-BPD under a variety of experimental conditions established that the 5E8 conjugate had specificity in terms of binding to A549 cells, and had significantly (p <0.01) greater efficacy in photodynamic killing in cytotoxicity assays. Further experiments were carried out to determine whether internalization of the BPD enhanced photodynamic killing. The results showed that internalized conjugate had much higher cytotoxicity than did surface associated. This was shown using two different model systems - 5E8 and the C7 antibody which has specificity for human low density lipoprotein (LDL) receptors. The final part of the thesis was involved in determining the fate of MoAb-PS conjugates in yyQ. Studies were carried out in A549 tumor bearing nude mice comparing the biodistribution of 5E8-M-PVA-BPD and T48-M-PVA-BPD. Both conjugates had biodistribution characteristics which distinguished them from free BPD in that they remained in the circulation and most tissues for significantly (p <0.01) longer times than did free BPD. With the exception of the 5E8-M-PVA-BPD conjugate and A549 tumor tissue, levels in all tissues were highest at the 3 h time point following injection of conjugates. In the case of the A549 tumor and the 5E8-M-PVA-BPD conjugate, the highest concentration of BPD was observed between 14 and 24 h following injection. Since the conjugates tested behaved differently from free BPD it was presumed that the material did not dissociate in and that the specific conjugate demonstrated specificity for the A549 tumor in terms of the kinetics of its accumulation in tumor tissue.

碩士<br>國立臺灣海洋大學<br>光電科學研究所<br>103<br>This thesis studied the influence of four different porphyrin derivatives on the conversion efficiency of solar cells using the blends of the porphyrin and PC71BM. The efficiencies of devices utilizing the active layer of YY1:PC71BM,CHH6:PC71BM ,CHH8:PC71BM and CHH9:PC71BM blends are 1.58 %,1.90 %,1.33 %,2.01 %, respectively. The active layer comprising CHH9:PC71BM blend shower the highest absorption strength. The solar cell using the CHH9:PC71BM blends exhibited the highest conversion efficiency. Moreover ,based on the AFM images ,the morphology of the active layer comprising CHH9:PC71BM blend showed the lowest value of surface roughness compared with that of active layer using YY1:PC71BM,CHH6:PC71BM or CHH8:PC71BM blends. This indicates the solubility of CHH9:PC71BM is better than that of YY1:PC71BM,CHH6:PC71BM,CHH8:PC71BM ,leading to the smoother morphology of the active layer and the improved the theirs the carrier transport property ,and enhanced device performance.

Since flavones present a diverse and vast list of biological activities, including antioxidant, anti-inflammatory, anticancer, antimicrobial, antiviral, antidiabetic, anti-allergic, activities or modulation of enzyme activity or metabolic pathways like the lipid metabolism, the synthesis of new flavones bearing uncommon patterns may be extremely useful. Though, these new flavone derivatives may be bioactive, one question needs to be answered, are they properly metabolized in biological systems? To answer that, biomimetic studies are a good strategy and synthetic porphyrins can be used in biomimetic oxidations. Simultaneously, these biomimetic oxidations can be a new way to obtain new flavones. In this work new flavones bearing naphthyl groups were obtained in good yields (> 60%). They were synthesised by the oxidative cyclization of the appropriated chalcone derivatives, which were obtained through a Claisen-Schmidt condensation in very good yields (> 70%). The biomimetic oxidation showed that only the 2-naphthyl moiety was oxidised, indicated that the benzochromenone scaffold is very stable. In addition, the biomimetic oxidation led to the synthesis of new flavone derivatives. One of the oxidation products was evaluated for its antioxidant and anti-cholinesterase activities, unfortunately the results showed that its activity is not significant. The characterization of all synthesised compounds was made by nuclear magnetic resonance (NMR) spectroscopic studies, including 1H and 13C, and two-dimensional heteronuclear correlated spectroscopy (HSQC and HMBC)<br>Uma vez que tanto as flavonas de origem natural como as obtidas sinteticamente, apresentam uma diversa e extensa lista de atividades biológicas que incluem antioxidante, anti-inflamatória, anticancerígena, antimicrobiana, antiviral, antidiabética ou modulação do metabolismo de lípidos, a síntese de novas flavonas contendo grupos pouco usuais pode ser extremamente relevante. Embora, estes novos derivados possam ser biologicamente ativos, há uma questão que carece de resposta, serão estes compostos devidamente metabolizados pelos sistemas biológicos? Estudos biomiméticos podem ser uma boa estratégia para encontrar a resposta e porfirinas sintéticas podem ser usadas na oxidação biomimética. Simultaneamente estas oxidações biomiméticas podem ser um novo método de síntese de novas flavonas. Neste trabalho foram sintetizadas novas flavonas contendo grupos naftilo, em bons rendimentos (> 60%). Estas foram obtidas através da ciclização oxidativa das respetivas calconas, que por sua vez foram sintetizadas por condensação de Claisen-Schmidt e obtidas em muito bons rendimentos (> 70%). A oxidação biomimética demonstrou que apenas os grupos 2-naftilo foram oxidados, sendo isto indicativo da maior estabilidade do núcleo benzocromenona. As atividades antioxidante e anti-colinesterase foram avaliadas, apenas para um dos produtos da oxidação biomimética, infelizmente os resultados não foram significativos. Todos os compostos sintetizados foram caracterizados por estudos de espectroscopia de ressonância magnética nuclear (RMN), incluindo espectros de 1H e 13C, e estudos bidimensionais de correlação espectroscópica heteronuclear (HSQC e HMBC)<br>Mestrado em Bioquímica

This dissertation focuses on two research projects. The first project examines the reactions of tungsten(VI) alkyl alkylidyne and bis-alkylidene complexes with phosphines and water and the studies of thermodynamics and kinetics of the reactions. These studies have been conducted in part to determine the mechanistic pathway in the formation of novel tungsten(VI) species. The second portion of this dissertation focuses on the spin density and structures of biomimetic Fe(III) porphyrin derivatives using neutron and X-ray diffraction techniques. The spin density and magnetic properties of an Fe(III) porphyrin derivative has been determined by polarized neutron diffraction. In the first portion of this dissertation, reaction of tungsten(VI) alkyl alkylidyne W(CH2SiMe3)3(≡CSiMe3) with Me2PCH2CH2PMe2 (DMPE), a bidentate phosphine, has been studied (Chapter 2). The reaction gives a DMPEalkylidyne adduct, which subsequently undergoes a tautomerization. The tautomeric mixture then converts to an alkyl alkylidene alkylidyne complex. Thermodynamic and kinetic studies as well as molecular modeling are used to understand these reactions. In Chapter 3, thermodynamic studies have been conducted of the addition of two mono-dentate phosphines to the tungsten(VI) alkyl alkylidyne complex. A reversible reaction has been observed with the mono-dentate phosphines. The reaction of tungsten(VI) alkyl alkylidyne W(CH2CMe3)3(≡CSiMe3) with H2O has been pursued. The reaction leads to the observation of the intermediate W2O2(µ-O)(CH2SiMe3)2(CH2CMe3)4 and subsequent formation of two oxo trimers. NMR spectroscopic studies have been used to determine the mechanistic pathway in formation of these trimeric complexes. In the second portion of this dissertation, variable-temperature X-ray studies have been conducted of Fe(TPP)Cl (TPP2- = meso-tetraphenylporphyrinate) (Chapter 5) and [Fe(TPP)(HIm)2]Cl (HIm = 1Himidazole) complexes (Chapter 6). The spin-density in the [Fe(TPP)(HIm)2]Cl (S = 1/2) complex has been probed using polarized neutron diffraction (Chapter 7). The study shows that the spin distribution of the unpaired electron is localized on the Fe(III) center. The Fe(TPP)Cl-d28 and [Fe(TPP)(DIm)2-d36]Cl complexes have been synthesized and characterized by X-ray diffraction (Chapter 8). A comparison is made between the protonated and per-deuterated X-ray diffraction structures.

博士<br>國立中興大學<br>物理學系所<br>98<br>In this research we investigate the transport and optical properties of three kinds of single crystals 5,10,15,20-tetrakis (4-N-ethylpyridyl) porphyrin salts (TEPyP-ions). The electrical conductivity exhibits high anisotropy, in that the conductivity along the stacking column, which is equal to 3.2 for sample TEPyP-4I, is three orders of magnitude larger than that perpendicular to the stacking column. In comparison to the solution spectra, the crystal spectra exhibit a blue shift of 0.09 eV in the B band and red shifts of 0.05 - 0.09 eV in the Q bands. The energy shifts are attributed to the exciton coupling interaction of the porphyrin molecules. Polarized reflectance measurements of the crystals reveal that the anisotropic reflectance is most intense when the light polarization is parallel to the molecular plane. The complex dielectric function and optical conductivity associated with each electronic transition are calculated based on analysis with a dielectric-function model. We also investigate the organic thin-film transistors fabricated employing the newly synthesized compound 5,10,15,20-(tetrakis(4-dodecoxylphenylethynyl)porphyrinato) zinc(II) (Zn-TDPP) as the active layer. The porphyrin was processed with side-chain substitution in the meso-position of the macrocycle. The organic film deposited by spin coating from a pyridine solution before being annealed in a furnace in argon gas to form homogenous polycrystals. Staggered source and drain gold contacts were made by argon ion sputtering with a stencil plate. The organic field-effect transistor (OFET) operates in the p-channel, accumulation-mode. The linear and saturation regimes were identified from the output and transfer characteristics. Carrier mobility, threshold voltage and ON/OFF ratio were calculated. The results show that the side-chain substitution greatly increased the solubility of the Zn-TDPP. The solution-processing technique can be used to fabricate porphyrin thin-film OFETs with a lower annealing temperature.

碩士<br>國立暨南國際大學<br>應用化學系<br>99<br>In this study, we synthesized a series of novel porphyrin dyes, and we studied their UV/Vis absorption and electrochemical properties. In our previous study, porphyrin dyes modified with pyrene, N-N-dimethylaniline or athracene as the substituent showed improved solar cell efficiencies. So we linked anthracene with pyrene or aniline derivatives as the substituent of porphyrin dyes, in order to further improve the efficiencies of the dyes. In order to improve the aggregation of porphyrin dyes on TiO2 surface, we chose two kinds of long alkoxy chain to modify the main chromophore of dye, and they are 5,15-dibromo-10,20-bis [3,4,5-tris(dodecyloxy)phenyl] porphinato zinc(II) and 5,15-dibromo-10,20-bis [3,4,5-bis(dodecyloxy)phenyl] porphinato zinc(II). Upon UV/Vis absorption, with anthracene combined with pyrene or aniline derivatives as the substituent of porphyrin dyes, the Soret and Q absorption bands of the novel porphyrins are red-shifted and broadened. Upon CV and DPV measurements, the reduction and oxidation potentials of these porphyrin dyes with the same main chormphore are similar. This suggests that with pyrene or aniline substituent have similar effects on the redox properties of the complexes. Significantly, the porphyrins with long alkoxyl chains attached at the ortho- positions of the phenyl group have more negative reduction and oxidation potentials than those with long alkoxyl chains attached at meta- and para- positions of the phenyl group. This suggests that the porphyrin dyes with long alkoxyl chains attached at the ortho- positions of the phenyl group would expect to have a higher HOMO and LUMO energy level. Thus, we would expect porphyrin dyes with ortho- substituents would expected have a higher Voc and better photovotaic performance.

碩士<br>國立中興大學<br>物理學系所<br>95<br>In this research, we study three kinds of derivative of new porphyrin –BPP [5,15-Bis(4-carboxylicphenyl) porphyrinato) zinc (II ) ] as the dyes of Dye-Sensitized Solar Cells (DSSCs). The new BPP dyes can absorb more solar light with a broader wavelength range. We prepared nanocrystalline TiO2 films from four kinds of TiO2 paste, and used N3 dye as the sensitizer for a basic production method of DSSCs. We were able to get a conversion efficiency of 6.4% using the Dyesol paste. The absorption spectra of [2-3-4N,N-Bia(4-methoxylphenyl)-N- (4-ethynylphenyl)amine] substituted BPP shift down to lower energies as the number of substituent is increased. The B band main absorption peak shifts from 413 to 451 nm (one substitute) and 472 nm (two substitutes); the Q band main absorption peak shifts from 543 to 624 nm (one substitute) and 676 nm (two substitutes). We report the current-voltage characteristic curves, fill factor (FF), shirt-circuit current Isc, open-circuit voltage Voc, and conversation efficiency η under the standard conditions of AM 1.5 incident light with 100 mW/cm2 power for the three types of porphyrin-derivative DSSCs . The parent BPP dye has the highest solar-to-energy conversion efficiency of η = 0.46%, and FF = 61.1%, ISC = 0.113 mA, VOC = 0.563 V were obtained.

Dissertação de Mestrado em Química apresentada à Faculdade de Ciências e Tecnologia<br>A questão ambiental e o desenvolvimento sustentável são uns dos grandes assuntos, tanto no cenário nacional como mundial. O conceito de desenvolvimento sustentável foi introduzido há cerca de 30 anos com o objetivo de satisfazer as necessidades do presente sem comprometer a capacidade das gerações futuras de satisfazerem as suas próprias necessidades, incluindo a capacidade de reduzir as consequências das substâncias que são produzidas e utilizadas. Nesse sentido, a química é essencial para garantir que a próxima geração de produtos e energia seja mais sustentável do que a atual. Deste modo, no início da década de 90, surgiu o conceito de Química Verde, tendo sido definido por Paul Anastas e John Warner como a invenção, desenvolvimento e aplicação de produtos químicos e processos, para reduzir ou eliminar o uso e a formação de substâncias perigosas à saúde humana e ao meio ambiente. A preocupação em desenvolver metodologias mais sustentáveis e que provoquem menos desperdícios tem levado os químicos orgânicos a ponderar métodos versáteis e altamente eficazes para promover as reações. Uma das técnicas que mais se tem desenvolvido e que se tem provado eficiente é a mecanoquímica. A ativação mecânica, normalmente realizada na ausência ou com o mínimo de solvente, aparece como uma alternativa para melhorar a sustentabilidade dos processos em Síntese Orgânica. Ao longo desta dissertação explorou-se a síntese de porfirinas e metaloporfirinas, desenvolvendo-se uma metodologia para a síntese de di-hidroporfirinas sob ação mecânica. A síntese via mecanoquímica permitiu a obtenção de clorinas com diversos substituintes, utilizando como agente redutor diimida, gerada in situ a partir de hidrato de hidrazina, com rendimentos semelhantes ou superiores aos métodos descritos na literatura. A utilização de hidrato de hidrazina, a eliminação do solvente e dos auxiliares de reação permitiu reduzir os tempos de reação e a formação de subprodutos. Assim, as novas metodologias aproximam-se dos princípios da Química Verde, sendo bastante evidente pela quantificação efetuada com recurso às métricas, Economia Atómica, E-Factor Completo e EcoScale.<br>Environmental issues and sustainable development are important national and international matters of our days. The concept of sustainable development was introduced about 30 years ago with the objective of covering the needs of the present without compromising the future generations’ ability to cover their own needs, including the capacity of reducing the consequences of the use and production of substances. In this point of view, chemistry is essential to ensure that the next generation of products and energy is more sustainable than the current. Thus, in the early 1990's, the concept of Green Chemistry was created by Paul Anastas and John Warner and was defined as the invention, development and application of chemical products and processes, to reduce or eliminate the use and formation of hazardous substances to humans’ health and the environment.The worry to put forth new more sustainable and less wasteful methods has led the organic chemists to consider versatile and highly effective methods to promote reactions. One of the most developed techniques that has been proven efficient is mechanochemistry. The mechanical activation, executed normally in the absence or with minimal use of solvents, appears as one of the best sustainable alternatives to the organic synthesis processes.Throughout this dissertation we explored the synthesis of porphyrins and metalloporphyrins and developed a methodology for the synthesis of dihydroporphyrins under mechanical activation.Synthesis via mechanochemistry allowed the production of chlorins with several substituents, using diimide as reducing agent, generated in situ from hydrazine hydrate, in yields similar or superior to those described in the literature. The use of hydrazine hydrate, the elimination of the solvent and the reaction auxiliaries allowed to reduce reaction times and the formation of by-products. Thus, the new methodologies approximate the principles of Green Chemistry, being quite evident by the quantification made using the metrics, Atomic Economy, E-Factor Complete and EcoScale.

碩士<br>國立中興大學<br>物理學系所<br>94<br>Abstract In this research , various nanocrystalline TiO2 films were prepared by the sol-gel method and the method of mixing commercial TiO2 nanometer powder. Structure and ingredients of the films were studied by FE-SEM,AFM and XRD; it was found that the characteristics of TiO2 films were related largely to the preparing techniques, crystalline form, crystalline size surface structure state of the TiO2 films can be controlled readily by varying the preparing procedures. The dye-sensitized solar cells (DSSC) were assembled with these films by N3 dye or porphyrin derivatives (5,15-Bis(4-carboxylicphenyl)porphyrinate)zinc(Ⅱ)-BPP dye, the KI/I2 electrolyte and a encounter electrode deposited as a platinum mirror. The optimized DSSC with N3 dye and anatase TiO2 of 0.23% exhibits a photo-to-electric conversion efficiency. The absorption spectrum of the BPP dye system shifts to visible after substitution ; the conversion efficiency enhances 2.1 times after.

碩士<br>國立暨南國際大學<br>應用化學系<br>100<br>In this thesis, we study reduction reactions of benzoic acid and zinc porphyrin derivatives in tetrahydrofuran. By adding H2O in tetrahydrofuran, we observed positive shift of the reduction potentials. In addition, we studied the influence of the long alkyl chains and electron-donating or withdrawing substituent on the reduction potentials of the carboxylic acid. As for the potentiostatic coulometry, we studied acid reductions by fixing the potentials upon electrolysis. However, we found no evidence of continuous hydrogen generation. The UV-visible absorption spectral titration of Zinc porphyrin titrated by TBAOH reveals that the first reduction reaction of ZnPE1 porphyrin in THF is actually the reduction of the carboxylic acid proton to hydrogen, not the reduction of the porphyrin itself.

博士<br>國立臺灣大學<br>化學研究所<br>101<br>We design a series of porphyrin derivatives with self-assembly motifs to study the correlation between molecular structure and self-assembled nanostructure. We use scanning electron microscopy and transmission electron microscopy as tools to identify the self-assembled structures of porphyrin derivatives. It is observed that the formation of different nano-morphologies such as nano-rod or hollow sphere can be manipulated either by the structural features and/or solvent compositions. In this regard, T-dicZnP with hydrophobic substitutions forms one-dimension rods, T-p-ditdiuZnP with hydrophilic substitutions gives hollow spheres. T-p-dicdiuZnP possessing the substituents of T-dicZnP and T-p-ditdiuZnP can interchange the nanostructure between one-dimension rods and hollow spheres through the control of solvent composition. We design a series of porphyrin isomers to map the correlation between molecular structure and self-assembled nanostructures. The porphyrin isomers form hollow spheres in protic solvent, but they give distinct nano-morphologies in aprotic solvent.