Complexos polipiridínicos de rutênio mononuclares vem sendo ativamente estudados como catalisadores da reação de oxidação de água a oxigênio, mas o complexo ativado dos catalisadores mais eficientes envolve a formação de um dímero, indicando a importância da estrutura binuclear para ativação dos mesmos. Assim, nesta tese propomos o estudo dos possíveis efeitos sinérgicos em complexos binucleares de rutênio polipiridinas angulares para ativação das espécies de alta valência do tipo RuV=O e RuIV=O. Assim, foram preparadas séries de complexos polipiridínicos de rutênio empregando os ligantes tridentados derivados de terpiridinas e bidentados tipo bipiridina na forma cloro complexos e aqua complexos mono e binucleares, capazes de atuar como precursores das espécies ativas de alta valência por meio de reações de transferência de elétrons acoplado a transferência de prótons (PCET). Os complexos [RuCl(bpy)(phtpy)](PF6), [Ru2Cl2(bpy)2(tpy2ph)](PF6)2 e [Ru2Cl2(Clphen)2(tpy2ph)](PF6)2 (phtpy= 4\'-fenil-2,2\':6\',2\'\'-terpiridina, bpy= 2,2´-bipiriridina, Clphen= 5-cloro-1,10-fenantrolina e tpy2ph= 1,3-bis(4\'-2,2\':6\',2\'\'-terpiridil)benzeno) e seus aqua complexos foram sintetizados e caracterizados por técnicas espectroscópicas e eletroquímicas. Os complexos [RuCl(bpy)phtpy](PF6), [Ru2Cl2(bpy)2(tpy2ph)](PF6)2 e [Ru2Cl2(Clphen)2(tpy2ph)](PF6)2 apresentam apenas reações de transferência de elétrons onde o estado de oxidação máximo do íon rutênio é 3+. Todavia, os respectivos aqua complexos [Ru(H2O)(bpy)(phtpy)](PF6)2, [Ru2(H2O)2(bpy)(tpy2ph)](PF6)4 e [Ru2(H2O)2(Clphen)2(tpy2ph)](PF6)4 podem ser oxidados de modo a gerar complexos de alta valência com íon rutênio nos estados de oxidação 4+ e 5+ via reação de transferência eletrônica acoplada a transferência de prótons (PCET). Os complexos de RuIV=O são gerados em potenciais relativamente baixos e não apresentaram atividade eletrocatalítica significativa, enquanto que as espécies RuV=O ([RuV(O)(bpy)(phtpy)]3+ e [Ru2V(O)2(bpy)2(tpy2ph)]6+) atuam como catalisadores eficientes para a reação de oxidação da água a oxigênio. Os valores de TOF para os complexos binuclear (0,97 s-1) é cerca de três vezes maior que para o complexo mononuclear (0,32 s-1), confirmando a presença de efeitos sinérgicos que aceleram a liberação de oxigênio no complexo binuclear. As propriedades eletrocatalíticas dos complexos polipiridínicos de rutênio de alta valência foram transferidos para a superfície de eletrodos via eletropolimerização redutiva do complexo [Ru2(H2O)2(Clphen)2(tpy2ph)](TfO)4. Neste caso foram observadas a geração eletroquímica de espécies contendo o íon rutênio nos estados de oxidação 2+, 4+ e 5+, enquanto que a espécie no estado 3+ aparentemente não é estável e sofre desproporcionamento. O eletrodo modificado preservou a alta atividade eletrocatalítica do aqua complexo binuclear para a reação de oxidação da água (TOF de 0,80 s-1) e também para a oxidação de álcool benzílico a benzaldeído, com kRuIV= 14,70 L·mol-1 s-1 demonstrando o elevado potencial do material para a oxidação de substratos orgânicos. / Mononuclear ruthenium polypyridyl complexes have been studied as catalysts of oxygen evolution in water oxidation reaction, but the activated complex of most efficient catalysts assume the formation of dimers indicating the importance of the binuclear structure for their activation. Thereby, in this thesis we propose the study of possible synergistic effects in binuclear ruthenium polypyridyl complexes in order to activate species with high valence as RuV=O and RuIV=O for multi-electronic catalytic oxidation reactions. For this purpose, it was prepared a series of ruthenium polyppyridyl complexes using tridentate ligands based in terpyridine and bidentate bipyridine generating binuclear chloride complexes and aqua complexes which are able to act as precursors of the respective high valence active species generated by proton coupled electron transfer (PCET) reactions. The [RuCl(bpy)(phtpy)](PF6) and [Ru2Cl2(bpy)2(tpy2ph)](PF6)2 complexes (phtpy= 4\'-phenyl-2,2\':6\',2\'\'-terpyridine, bpy= 2,2´-bipyridine and tpy2ph= 1,3-bis(4\'-2,2\':6\',2\'\'-terpyridin-4-yl)benzene) and their respective aqua complexes were synthetized and characterized by spectroscopic and electrochemical techniques. The chloro complexes [RuCl(bpy)(phtpy)](PF6), [Ru2Cl2(bpy)2(tpy2ph)](PF6)2 and [Ru2Cl2(Clphen)2(tpy2ph)](PF6)2 (Clphen= 5-Chloro-1,10-phenanthroline) show only electron transfer reactions where the maximum oxidation state of the ruthenium ion is 3+. However, the respective aqua complexes [Ru(H2O)(bpy)(phtpy)](PF6)2, [Ru2(H2O)2(bpy)2(tpy2ph)](PF6)4 and [Ru2(H2O)2(Clphen)2(tpy2ph)](PF6)4 can be oxidized further by proton coupled electron transfer (PCET), generating high valence complexes where the ruthenium oxidation state can be 4+ and 5+. Complexes of RuIV=O are generated in relatively low potentials and do not presented significant electrocatalytic activity for oxidation of water to dioxygen, whereas the RuV=O species ([RuV(O)(bpy)(phtpy)]3+ and [Ru2V(O)2(bpy)2(tpy2ph)]6+) showed to be efficient catalysts for the reaction of water oxidation. The values of TOF for the binuclear complexes (0,97 s-1) were about three times larger than for the mononuclear complex (0,32 s-1), confirming the presence of synergistic effects accelerating the formation and release of oxygen by the binuclear complex. The electrocatalytic properties of high valence ruthenium polypyridyl complexes were transferred to electrodes surface by reductive electropolymerization of the [Ru2(H2O)2(Clphen)2(tpy2ph)](TfO)4 complex. In this case the electrochemical generation of ruthenium 2+, 4+ and 5+ species were observed whereas the 3+ species was not stable and disproportionated. The modified electrodes preserved the high electrocatalytic activity of the binuclear aqua complexes for water oxidation reaction (TOF de 0,80 s-1), and also for oxidation of benzyl alcohol to benzaldehyde with kRuIV= 14,70 L mol-1 s-1 demonstrating the high catalytic efficiency for oxidation of organic substrates.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Complexos de bipiridinas de rutÃnio sÃo bastante estudados na literatura por apresentarem propriedades de interesse em diversas Ãreas como estudos fotoquÃmicos e fotofÃsicos, aplicaÃÃo em sistemas biolÃgicos e como fotosensibilizadores em cÃlulas solares. No presente trabalho, os complexos do tipo cis-[Ru(bpy)(dcbH2)(L)Cl], onde L = Azul do Nilo (NB), Azul de Toluidina (TBO), 9-Aminoacridina (9AA), Azure B (AB) e Violeta de Cresila (VC) foram sintetizados e caracterizados por tÃcnicas espectroscÃpicas e eletroquÃmica para aplicaÃÃo em cÃlulas solares sensibilizadas por corante (DSCs). AlÃm destes, o complexo cis-[Ru(dcbH2)(bpy)(TCNE)Cl] (Ru-TCNE) tambÃm foi testado como sensibilizador em DSC. Estes compostos apresentaram bandas de transferÃncia de carga do tipo MLCT na regiÃo do visÃvel e potenciais redox termodinamicamente favorÃveis para as reaÃÃes de transferÃncia de carga que ocorrem no dispositivo fotoeletroquÃmico. A adsorÃÃo quÃmica dos complexos sensibilizadores na superfÃcie do TiO2 foi evidenciada pelo deslocamento das bandas de MLCT para regiÃes de menor energia quando comparadas aos espectros em soluÃÃo. Os desempenhos fotovoltaicos dos complexos como sensibilizadores em DSC foram avaliados atravÃs das curvas corrente versus potencial, obtidas em condiÃÃes padrÃo AM 1,5. As DSCs contendo os sensibilizadores Ru-TBO e Ru-AB apresentaram os menores desempenhos fotovoltaicos com eficiÃncia global de 0,02 e 0,06%, respectivamente. JÃ as cÃlulas solares sensibilizadas pelos corantes Ru-NB e Ru-VC obtiveram um rendimento de 0,11% com baixos valores de eficiÃncia de incidÃncia de conversÃo de fÃtons a corrente, IPCE. Os melhores resultados foram para as cÃlulas contendo os corantes Ru-9AA e Ru-TCNE, as quais apresentaram rendimentos de 0,54 e 2,01%, respectivamente, com valores de IPCE iguais a 10% para Ru-9AA e 48% para Ru-TCNE. Todos os complexos apresentaram eficiÃncia global de conversÃo de energia solar em elÃtrica inferiores ao complexo padrÃo N3. / Bipyridines ruthenium complexes are widely studied in the literature for presenting interesting properties in various fields such as photochemical and photophysical studies, applications in biological systems and as photosensitizers in solar cells. In this work, the complexes of the type cis-[Ru(bpy)(dcbH2)(L)Cl], where L = Nile blue (NB), Toluidine blue (TBO), 9-aminoacridine (9AA), Azure B (AB) and Cresyl Violet (VC) were synthesized and characterized by spectroscopic and electrochemical techniques for application in dye-sensitized solar cells (DSC). In addition, the complex cis-[Ru(dcbH2)(bpy)(TCNE)Cl] (Ru-TCNE) was also tested as a sensitizer DSC. These compounds showed bands of charge transfer type MLCT in the visible region and thermodynamically favorable redox potentials for the charge transfer reactions which occur in the photoelectrochemical device. The adsorption of the chemical sensitizers complexes on the surface of TiO2 was evidenced by displacement of MLCT bands to lower-energy when compared to the spectra in solution. The photovoltaic performances of the complexes as sensitizers in DSC were evaluated through current versus potential curves obtained in standard AM 1.5 conditions. The DSC sensitizers containing Ru-TBO and Ru-AB had the lowest overall efficiency with photovoltaic performances of 0.02 and 0.06%, respectively. As for the dye-sensitized solar cells by Ru-NB and Ru-VC obtained a yield of 0.11% with low efficiency values of incident conversion of photon to current, IPCE. The best results were for cells containing the dyes Ru-9AA and Ru-TCNE, with energy conversion efficiency of 0.54 and 2.01%, respectively, with IPCE values equal to 10% for Ru-9AA and 48% for Ru-TCNE moieties. All complexes showed overall efficiency of converting solar energy into electricity below the N3 complex pattern.

La Tesi descriu de manera completa una sèrie de complexos de ruteni amb lligands polipiridílics i lligands auxiliars de tipus fosfina, dmso, nitril o aquo. Es descriuen estudis d'isomerització (cis/trans o coordinació meridional/facial) en complexos mononuclears, a partir de tècniques espectroscòpiques. Els resultats experimentals es corroboren a partir de càlculs DFT. S'han fet també estudis d'activitat catalítica en transferència d'hidrogen per als complexos Ru-fosfina. S'han sintetitzat també complexos dinuclears de ruteni amb el lligand tetradentat Hbpp i s'ha avaluat llur activitat en la catàlisi d'oxidació d'aigua, determinant la importància de la correcta orientació relativa dels centres actius Ru=O. L'heterogeneïtzació dels complexos sobre suports conductors permet avaluar llur activitat en fase heterogènia, millorant respecte el corresponent procés en dissolució. La co-polimerització dels catalitzadors amb espècies de tipus metalocarborà, amb major dilució del catalitzador i minimització de la sobreoxidació, millora notablement els resultats, permetent diverses reutilitzacions. / A number of ruthenium complexes having polypyridilic ligands together with phosphine, dmso, nitrile or aquo ligands are described. Isomerization processes (cis/trans or meridional/facial coordination) are studied for mononuclear complexes through spectroscopic techniques. The experimental results are confirmed by DFT calculations. Catalytic activity in transfer hydrogen reactions have also been evaluated for Ru-phosphine complexes. Dinuclear complexes containing the tetradentate Hbpp ligand have also been synthesized, and their catalytic activity in water oxidation catalysis has been tested, concluding that a right relative orientation of the active Ru=O sites is a key factor. Heterogenisation of catalysts over conducting supports allows evaluating their activity in heterogeneous phase, showing an improvement with regard to systems in solution. The co-polymerization of catalysts with metallocarborane monomers, involving higher catalyst dilution and minimization of sobreoxidation processes noticeably improves the results, also allowing several reutilizations.

Submitted by Regina Correa (rehecorrea@gmail.com) on 2016-09-19T14:14:44Z No. of bitstreams: 1 DissIPV.pdf: 1704019 bytes, checksum: 751e447a48fee6a71450395588fde1ab (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-23T18:19:29Z (GMT) No. of bitstreams: 1 DissIPV.pdf: 1704019 bytes, checksum: 751e447a48fee6a71450395588fde1ab (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-23T18:19:35Z (GMT) No. of bitstreams: 1 DissIPV.pdf: 1704019 bytes, checksum: 751e447a48fee6a71450395588fde1ab (MD5) / Made available in DSpace on 2016-09-23T18:19:41Z (GMT). No. of bitstreams: 1 DissIPV.pdf: 1704019 bytes, checksum: 751e447a48fee6a71450395588fde1ab (MD5) Previous issue date: 2016-04-14 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / The endothelium is a monolayer of cells that extends on the vascular inner surface, responsible for the modulation of vascular tone. By means of the release of nitric oxide (NO), the endothelium has an important protective function against cardiovascular diseases, producing vasodilation by several mechanisms and generating a series of other effects, since at high concentrations it may produce toxic effects to the cells. However, endothelial dysfunction is characterized mainly by the decreased ability of endothelial cells to release NO, which may be due to reaction with superoxide anion (O2 -) and formation of peroxynitrite (ONOO-). In previous studies, it was found that ruthenium complexes can also inactivate O2 - and NO release. However, through vascular reactivity technique in aortic hypertensive and normotensive rats, and detection study of released NO in endothelial cells, the objective of this study was to evaluate the potential of the drug cis- [Ru(bpy)2(NO2)(NO)](PF6)2 as a pharmacologic strategy to reverse and/or prevent endothelial dysfunction found in the arterial hypertension model 2K-1C as well as to perform the pharmacological characterization of the dependent effects removal of O2 - and NO release induced by these drugs. Thus our major vascular reactivity results indicated that the BPY concentration of 0.1 μM was able to reverse the endothelial dysfunction present in the aortas of animals 2K-1C. Likewise, its positive control, Deta-NO in a specific concentration of 10 μM was able to reverse endothelial dysfunction, besides presenting a potentiating effect in the presence of endothelium. Furthermore, our results indicate that the lowest detection of NO in HUVECs treated with Ang. II, in addition to BPY compound occurs by the increased formation of O2 -, since in the presence of SOD there was an increased release of NO by BPY. Furthermore, it was observed that the BPY releases NO in solution in a sustained concentration-dependent form, where the presence of the endothelial cells increased and Angiotensin II reduces NO release, indicating a reduction or oxidation in BPY compound and also degradation of NO the formation of O2 -. / O endotélio é uma monocamada de células que se estende sobre a superfície interna vascular, responsável pela modulação do tônus vascular. Por meio da liberação do óxido nítrico (NO), o endotélio apresenta importante função protetora contra as doenças cardiovasculares, produzindo vasodilatação por diversos mecanismos e gerando uma série de outros efeitos, visto que em altas concentrações pode produzir efeitos tóxicos às células. Contudo, a disfunção endotelial é caracterizada principalmente pela diminuição da capacidade das células endoteliais em liberar NO, que pode ser decorrente da reação com ânion superóxido (O2 -) e formação de peroxinitrito (ONOO-). Em estudos prévios, foi verificado que complexos de rutênio podem inativar O2 - e também liberar NO. Contudo através de técnica de reatividade vascular em aorta de ratos hipertensos e normotensos, e estudo de detecção de NO liberado em células endoteliais, o objetivo do presente estudo foi avaliar o potencial da droga cis-[Ru(bpy)2(NO2 -)(NO)](PF6)2 como estratégia farmacológica para reverter e/ou prevenir a disfunção endotelial encontrada no modelo de hipertensão arterial 2R-1C, bem como realizar a caracterização farmacológica dos efeitos dependentes da remoção do O2 - e liberação do NO induzidos por estas drogas. Desta forma os principais resultados de reatividade vascular indicaram que o BPY na concentração de 0,1 μM foi capaz de reverter a disfunção endotelial presente nas aortas de animais 2R-1C. Da mesma forma, seu controle positivo, Deta-NO, em uma concentração específica 10 μM, foi capaz reverter a disfunção endotelial, além de apresentar potencialização de seus efeitos na presença do endotélio. Além disso, houve menor detecção de NO em HUVECs tratadas com Ang. II, além do composto BPY, ocorre pela maior formação de O2 -, uma vez que na presença de SOD ocorreu aumento na liberação de NO pelo BPY. Ainda, observou–se que o BPY libera NO em solução de forma concentração dependente e prolongada, em que a presença das células endoteliais aumentou a liberação de NO e a angiotensina II reduz sua liberação de NO, indicando redução ou oxidação no composto BPY e degradação do NO pela formação do O2 -.

Submitted by Cláudia Bueno (claudiamoura18@gmail.com) on 2015-10-26T16:54:27Z No. of bitstreams: 2 Tese - Flávia de Castro Pereira - 2014.pdf: 7274098 bytes, checksum: 2478fc770e9bfbd8ffb6361d038b525d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2015-10-27T14:38:45Z (GMT) No. of bitstreams: 2 Tese - Flávia de Castro Pereira - 2014.pdf: 7274098 bytes, checksum: 2478fc770e9bfbd8ffb6361d038b525d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-10-27T14:38:45Z (GMT). No. of bitstreams: 2 Tese - Flávia de Castro Pereira - 2014.pdf: 7274098 bytes, checksum: 2478fc770e9bfbd8ffb6361d038b525d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-03-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The resistance acquired by some tumor cell lines retricts the use of drugs made of platinum because of Ruthenium compounds have been objects of great attention for presenting antimetastatic properties and low toxicity. Ruthenium compounds form compounds with the most different chemical binders, presenting good behavior and expanding the possibilities offor biological applications. A wide variety of coordination has enabled studies on ruthenium complexes, andseveral oxidation stages (Ru (II), Ru (III), and Ru (IV)) under physiological conditions and the rate of binder substitution. This study ranges the citotoxic activity of ruthenium (III) compound cis- Tetraammine(oxalato)Ruthenium(III) Dithionate - {Cis-[Ru(C2O4)(NH3)4]2(S2O6)} to treat human erythroleukemia (K562) tumor cell lineand the complex of ruthenium (II) coordinated a phosphine ligand and nitrile front tumor lineage S180 through the techniques of assay cell viability, assay kinetics of cell cycle phases, annexin V assay/ propidium iodide, test of mitochondrial membrane potential, test comet and gene expression through real time PCR. Both antiproliferative and cytotoxic activity revealed that K562 cells cultured with ruthenium (III) compound showed meaningful decrease in proliferation. Ruthenium(III) compound induced the IC50 value was of 18.28 μM set againts the cell cycle profiles cells not treated. Flow cytometric analysis indicated a sub-G1 arresting effect of ruthenium compound on K562 cells. Through the cell viability assay through MTT reduction technique, it was found that the complex of ruthenium (II) phosphine coordinated and nitrile presented cytotoxic activity when facing the tumor strain S180 with IC50 17.02±8.21μM and IC50 de 53.73 ± 5.71 μM for lymphocyte. When analyzing the cell cycle of tumor cells S180 treated with complex of ruthenium (II) caused increase in cells in G0/G1 and in S phase decreased. We observed an increase G2 / M. In the analysis of apoptosis assays, the results pointed that the complex ruthenium (II) induced cell death via apoptosis in tumor strain S180 as proved the increase in annexin cells V positive, depolarization of the mitochondrial membrane potential, activation of caspase 3 (Casp3) and 8 (Casp8) and increased expression levels of caspase-3 (Casp3) (mRNA), Bax (mRNA) and Tp53. The results lead to the conclusion that both complexes of ruthenium (II) and (III) induce cytotoxic activity against cell models tested, and that this activity correlates with alterations in cell cycle phases and induction of cell death via apoptosis. / Fármacos à base de cisplatina ainda são os anticancerígenos mais utilizados no mundo. Os compostos de rutênio têm sido objetos de grande atenção devido as suas propriedades antimetastática, baixa toxicidade e vários estados de oxidação (Ru (II), Ru (III) e Ru (IIV)) em condições fisiológicas. O presente trabalho teve como objetivo investigar in vitro os efeitos citotóxico e mecanismo de morte do complexo Ditionato de cis-Tetraamino(oxalato)rutênio(III) na linhagem tumoral de leucemia mielóide crônica (K562) e do complexo de rutênio (II) coordenado a ligante fosfina e nitrila [RuCl(bcn)(bipy)(dppe)]PF6, em linhagem tumoral S180 a partir das técnicas de ensaio de viabilidade celular, ensaio de cinética das fases do ciclo celular, ensaio anexina V/Iodeto de Propídeo, ensaio de potencial de membrana mitocondrial e expressão gênica por PCR em tempo real. Os resultados mostraram que o complexo de rutênio (III) provoca uma significativa redução na proliferação de células K562. O complexo de rutênio (III) induziu uma IC50 =18,28 μM. A análise por citometria de fluxo indicou um efeito sub-G1 dos complexos de rutênio sobre células de K562. O composto provocou um aumento de dano significativo nas células em todas as concentrações testadas em comparação ao controle negativo, o que pode ser associado à citotoxicidade com efeito direto sobre o DNA das células de K562. A partir do ensaio de viabilidade celular pela técnica de redução do MTT, verificou-se que o complexo de rutênio (II) coordenado a fosfina e nitrila apresentou atividade citotóxica frente à linhagem tumoral S180 com IC50 17,02±8,21μM e IC50 de 53,73 ± 5,71 para linfócito. Na análise do ciclo celular de células tumorais S180 tratadas com o complexo de rutênio (II), casou indução de G0/G1, fase S e G2/M. Na análise dos ensaios de apoptose, os resultados demonstraram que o complexo de rutênio (II) induziu morte celular via apoptose na linhagem tumoral S180, como evidenciado pelo aumento no número de células anexina V positivo, despolarização do potencial de membrana mitocondrial, ativação das caspase 3 (Casp3) e 8 (Casp8) e aumento dos níveis de expressão de caspase-3 (Casp3) (mRNA), Bax (mRNA) e Tp53 . A partir dos resultados conclui-se que ambos os complexos de rutênio (II) e (III) induzem atividade citotóxica frente aos modelos de células testadas, sendo que a atividade está correlacionada às alterações nas fases do ciclo celular e indução de morte celular via apoptose.

Complexos polipiridínicos de rutênio mononuclares vem sendo ativamente estudados como catalisadores da reação de oxidação de água a oxigênio, mas o complexo ativado dos catalisadores mais eficientes envolve a formação de um dímero, indicando a importância da estrutura binuclear para ativação dos mesmos. Assim, nesta tese propomos o estudo dos possíveis efeitos sinérgicos em complexos binucleares de rutênio polipiridinas angulares para ativação das espécies de alta valência do tipo RuV=O e RuIV=O. Assim, foram preparadas séries de complexos polipiridínicos de rutênio empregando os ligantes tridentados derivados de terpiridinas e bidentados tipo bipiridina na forma cloro complexos e aqua complexos mono e binucleares, capazes de atuar como precursores das espécies ativas de alta valência por meio de reações de transferência de elétrons acoplado a transferência de prótons (PCET). Os complexos [RuCl(bpy)(phtpy)](PF6), [Ru2Cl2(bpy)2(tpy2ph)](PF6)2 e [Ru2Cl2(Clphen)2(tpy2ph)](PF6)2 (phtpy= 4\'-fenil-2,2\':6\',2\'\'-terpiridina, bpy= 2,2´-bipiriridina, Clphen= 5-cloro-1,10-fenantrolina e tpy2ph= 1,3-bis(4\'-2,2\':6\',2\'\'-terpiridil)benzeno) e seus aqua complexos foram sintetizados e caracterizados por técnicas espectroscópicas e eletroquímicas. Os complexos [RuCl(bpy)phtpy](PF6), [Ru2Cl2(bpy)2(tpy2ph)](PF6)2 e [Ru2Cl2(Clphen)2(tpy2ph)](PF6)2 apresentam apenas reações de transferência de elétrons onde o estado de oxidação máximo do íon rutênio é 3+. Todavia, os respectivos aqua complexos [Ru(H2O)(bpy)(phtpy)](PF6)2, [Ru2(H2O)2(bpy)(tpy2ph)](PF6)4 e [Ru2(H2O)2(Clphen)2(tpy2ph)](PF6)4 podem ser oxidados de modo a gerar complexos de alta valência com íon rutênio nos estados de oxidação 4+ e 5+ via reação de transferência eletrônica acoplada a transferência de prótons (PCET). Os complexos de RuIV=O são gerados em potenciais relativamente baixos e não apresentaram atividade eletrocatalítica significativa, enquanto que as espécies RuV=O ([RuV(O)(bpy)(phtpy)]3+ e [Ru2V(O)2(bpy)2(tpy2ph)]6+) atuam como catalisadores eficientes para a reação de oxidação da água a oxigênio. Os valores de TOF para os complexos binuclear (0,97 s-1) é cerca de três vezes maior que para o complexo mononuclear (0,32 s-1), confirmando a presença de efeitos sinérgicos que aceleram a liberação de oxigênio no complexo binuclear. As propriedades eletrocatalíticas dos complexos polipiridínicos de rutênio de alta valência foram transferidos para a superfície de eletrodos via eletropolimerização redutiva do complexo [Ru2(H2O)2(Clphen)2(tpy2ph)](TfO)4. Neste caso foram observadas a geração eletroquímica de espécies contendo o íon rutênio nos estados de oxidação 2+, 4+ e 5+, enquanto que a espécie no estado 3+ aparentemente não é estável e sofre desproporcionamento. O eletrodo modificado preservou a alta atividade eletrocatalítica do aqua complexo binuclear para a reação de oxidação da água (TOF de 0,80 s-1) e também para a oxidação de álcool benzílico a benzaldeído, com kRuIV= 14,70 L·mol-1 s-1 demonstrando o elevado potencial do material para a oxidação de substratos orgânicos. / Mononuclear ruthenium polypyridyl complexes have been studied as catalysts of oxygen evolution in water oxidation reaction, but the activated complex of most efficient catalysts assume the formation of dimers indicating the importance of the binuclear structure for their activation. Thereby, in this thesis we propose the study of possible synergistic effects in binuclear ruthenium polypyridyl complexes in order to activate species with high valence as RuV=O and RuIV=O for multi-electronic catalytic oxidation reactions. For this purpose, it was prepared a series of ruthenium polyppyridyl complexes using tridentate ligands based in terpyridine and bidentate bipyridine generating binuclear chloride complexes and aqua complexes which are able to act as precursors of the respective high valence active species generated by proton coupled electron transfer (PCET) reactions. The [RuCl(bpy)(phtpy)](PF6) and [Ru2Cl2(bpy)2(tpy2ph)](PF6)2 complexes (phtpy= 4\'-phenyl-2,2\':6\',2\'\'-terpyridine, bpy= 2,2´-bipyridine and tpy2ph= 1,3-bis(4\'-2,2\':6\',2\'\'-terpyridin-4-yl)benzene) and their respective aqua complexes were synthetized and characterized by spectroscopic and electrochemical techniques. The chloro complexes [RuCl(bpy)(phtpy)](PF6), [Ru2Cl2(bpy)2(tpy2ph)](PF6)2 and [Ru2Cl2(Clphen)2(tpy2ph)](PF6)2 (Clphen= 5-Chloro-1,10-phenanthroline) show only electron transfer reactions where the maximum oxidation state of the ruthenium ion is 3+. However, the respective aqua complexes [Ru(H2O)(bpy)(phtpy)](PF6)2, [Ru2(H2O)2(bpy)2(tpy2ph)](PF6)4 and [Ru2(H2O)2(Clphen)2(tpy2ph)](PF6)4 can be oxidized further by proton coupled electron transfer (PCET), generating high valence complexes where the ruthenium oxidation state can be 4+ and 5+. Complexes of RuIV=O are generated in relatively low potentials and do not presented significant electrocatalytic activity for oxidation of water to dioxygen, whereas the RuV=O species ([RuV(O)(bpy)(phtpy)]3+ and [Ru2V(O)2(bpy)2(tpy2ph)]6+) showed to be efficient catalysts for the reaction of water oxidation. The values of TOF for the binuclear complexes (0,97 s-1) were about three times larger than for the mononuclear complex (0,32 s-1), confirming the presence of synergistic effects accelerating the formation and release of oxygen by the binuclear complex. The electrocatalytic properties of high valence ruthenium polypyridyl complexes were transferred to electrodes surface by reductive electropolymerization of the [Ru2(H2O)2(Clphen)2(tpy2ph)](TfO)4 complex. In this case the electrochemical generation of ruthenium 2+, 4+ and 5+ species were observed whereas the 3+ species was not stable and disproportionated. The modified electrodes preserved the high electrocatalytic activity of the binuclear aqua complexes for water oxidation reaction (TOF de 0,80 s-1), and also for oxidation of benzyl alcohol to benzaldehyde with kRuIV= 14,70 L mol-1 s-1 demonstrating the high catalytic efficiency for oxidation of organic substrates.

O óxido nítrico (NO) é um versátil agente biológico, atuando em diversas partes do organismo, tais como cérebro, artérias, sistema imunológico, fígado e pulmões. Sua natureza radicalar lhe confere grande reatividade e versatilidade, tornando o entendimento de sua bioquímica um desafio. A molécula de NO tende a reagir rapidamente com alguns metais de transição, formando compostos estáveis denominados complexos nitrosilos, os quais podem ser utilizados como fonte geradora de óxido nítrico. A liberação de NO a partir de complexos nitrosilos pode ocorrer por redução química, eletroquímica e fotoquímica. No presente trabalho foi estudada a obtenção, caracterização e permeação cutânea de um complexo nitrosilo de rutênio, o trans-[RuC(cyclam)(NO)]C2 (cyclam-NO), que associado ao fotossensibilizador protoporfirina IX, possui a peculiaridade de absorver na região do visível, podendo então ser aplicados na terapia fotodinâmica (TFD) para tratamento de câncer de pele. A mistura dos compostos foi incorporada em nanodispersões de cristais líquidos, de fase cúbica (DFC) e de fase hexagonal (DFH), e sua penetração/permeação in vitro em pele de modelo animal foi avaliada, assim como o comportamento fotoquímico do sistema, no que se refere à liberação de NO, visando uma futura aplicação em TFD. A atividade citotóxica dos compostos isolados e em mistura foi avaliada frente às linhagens B16F10 e Melan-A, na ausência e presença de luz, mostrando maior atividade da mistura dos compostos quando irradiados em 630 nm. Foram construídos diagramas de fase binário e ternário e, a partir destes, foram escolhidas as formulações a serem estudadas. Estas formulações foram caracterizadas por microscopia de luz polarizada e difração de raios-X e foram avaliados o tamanho médio de partícula e o índice de polidispersividade das nanodispersões obtidas e sua estabilidade por turbidimetria. Também foi analisada a liberação de oxigênio singlete e de NO a partir dos compostos em solução e destes incorporados nas formulações. Foi desenvolvido e validado um método analítico por cromatografia líquida de alta eficiência para a quantificação simultânea dos compostos nos experimentos. A liberação dos compostos a partir das formulações usando membrana de acetato de celulose também foi avaliada, sendo possível detectar apenas o cyclam-NO. O estudo da eficiência de encapsulação mostrou que cerca de 70% da quantidade adicionada dos compostos foi incorporado na DFC e cerca de 80% na DFH. Os experimentos in vitro de permeação e retenção dos compostos em pele de orelha de porco mostraram aumento significativo da concentração dos compostos, comparado a controles contendo os mesmos em PEG. A DFH promoveu um aumento na concentração de PpIX no estrato córneo (EC) de 2,6 vezes e na epiderme+derme se EC ([E+D]) de 3,4 vezes, e para o cyclam-NO de 2,7 vezes no EC e 2,4 vezes na [E+D]. Já a DFC aumentou em 1,6 vezes a quantidade de PpIX no EC e 1,9 vezes na [E+D] e em 4,6 vezes a quantidade de cyclam-NO no EC e em 2,0 vezes na [E+D]. Os resultados obtidos permitem sugerir que estes sistemas são adequados para utilização como potenciais carreadores para a associação cyclam-NO e PpIX na TFD do câncer de pele e que esta associação apresentou efeito sinérgico, sendo mais eficiente que a utilização de apenas um dos compostos. / Nitric oxide (NO) is a versatile biological agent, acting in several parts of the body such as brain, arteries, immune system, liver and lungs. Its radical nature gives great versatility and reactivity, making the understanding of its biochemical a challenge. The NO molecule tends to react quickly with some transition metals, forming stable compounds called nitrosyl complexes, which can be used as a source of nitric oxide. NO release from nitrosyl complexes can occur by chemical, electrochemical or photochemical reduction. In this work, the acquisition, characterization and permeation of a nitrosyl ruthenium complex, trans-[RuC(cyclam)(NO)]C2 (cyclam-NO), which associated with the photosensitizer protoporphyrin IX, has the peculiarity of absorbing in the visible region, and could then be applied in photodynamic therapy (PDT) for treatment of skin cancer, were studied. The mixture of compounds was incorporated into liquid crystal nanodispersions, cubic (DFC) and hexagonal (DFH) phases, and its penetration/permeation in vitro in an animal model skin was evaluated, as well as the photochemical behavior of the system, with regard to NO release, seeking a future application in PDT. The cytotoxic activity of the compounds alone and in combination was evaluated against the B16F10 and Melan-A cell lines, in the absence and in the presence of light. Binary and ternary phase diagrams were constructed, and from these, the formulations to be studied were chosen. These formulations were characterized by polarized light microscopy and X-ray diffraction and were evaluated for particle size and polydispersity index of nanodispersions obtained and their stability by turbidimetry. Also, the release of singlet oxygen and NO from the compounds in solution and incorporated in the formulations was discussed. An analytical method using high efficiency liquid chromatography was developed and validated for simultaneous quantification of compounds in the experiments. The release of compounds from formulations using cellulose acetate membrane was evaluated, and only the cyclam-NO could be detect. The study of the encapsulation efficiency showed that about 70% of the added amount of the compounds was incorporated in the DFC and approximately 80% in DFH. In vitro permeation and retention experiments of the compounds in pig ear skin were performed, showing a significant increase in the concentration of the compounds in the skin layers, compared to controls containing compounds in polyethylene glycol. The DFH promoted an increase in the concentration of PpIX in the stratum corneum (EC) of 2.6 times and in the epidermis + dermis without EC ([E + D]) of 3.4 times, and the cyclam-NO by 2.7 times for EC and 2.4 times in the [E + D]. DFC already increased by 1.6 times the amount of PpIX in EC and 1.9 times at the [E+D] and 4.6 times the amount of cyclam-NO in EC and 2.0 times in the [E + D]. The results may suggest that these systems are suitable for use as potential carriers for the association of cyclam-NO and PpIX for use in skin cancer PDT and that this association showed a synergistic effect, being more efficient than the use of only one of the compounds.

Ce travail est consacré à la synthèse et la caractérisation des commutateurs et des fils moléculaires incorporant l'unité et le ruthénium organométalliques fractions photochromiques. La première partie traite de lanthanides complexe Yb combiné avec l'unité et le ruthénium acétylure fractions photochromiques afin de moduler la luminescence avec l'aide de redox et de stimuli lumineux. Dans la deuxième partie explique la combinaison d'unités DTE photochromiques avec des fragments acétylures de ruthénium pour fixer sur la surface de nanoparticules métalliques afin d'affiner leur résonance plasmonique grâce à la modification de l'environnement de surface en utilisant la lumière et redox stimuli. La troisième partie décrit la préparation de complexes de lanthanides combinés avec une unité photochromique spiropyranne pour commuter les propriétés SMM des complexes via photoisomérisation de l'unité spiropyranne. Dans la dernière partie, nous présentons la synthèse de Oligo (phénylène éthylène) Les fils moléculaires avec différents noyaux centraux afin d'obtenir une variété de fil avec différents niveaux d'énergie HOMO-LUMO pour vérifier l'effet de l'épinglage. / This work is devoted to the synthesis and characterization of novel molecular switches and wires incorporating photochromic unit and ruthenium organometallic moieties. The first part deals with lanthanide Yb complex combined with photochromic unit and ruthenium acetylide moieties in order to modulate the luminescence with the help of redox and light stimuli. In the second part explained the combination of photochromic DTE units with ruthenium acetylide moieties to attach on the surface of metal nanoparticles in order to tune their plasmonic resonance through the surface environment modification by using light and redox stimuli. The third part describes the preparation of lanthanide complexes combined with a spiropyran photochromic unit in order to switch the SMM properties of the complexes via photoisomerization of the spiropyran unit. In the last part, we report the synthesis of Oligo(phenylene ethylene) molecular wires with different central cores in order to obtain various wire with different HOMO-LUMO energy levels to check the effect of pinning.

Les processus d’oxydation et d’amination sont très importants dans le monde de l’industrie mais les procédés actuels sont polluants. Afin de réaliser ces transformations de manière catalytique et propre, les réactions bioinspirées par transfert d’atome d’oxygène (TAO) et d’azote (TAN) ont été étudiées. La formation de l’espèce active à haut degré d’oxydation étant bien connue dans le cas des TAO, l’enjeu se situe dans le design des ligands. Dans le cas des TAN, cette étape est moins bien étudiée, limitant le développement de nouveaux catalyseurs. Enfin, l’utilisation d’une source d’énergie lumineuse, et non plus chimique, est recherchée afin de diminuer les déchets produits lors de ces réactions.Deux stratégies ont été mises en œuvre au cours de ce projet. Pour l’étude des réactions par TAO, deux nouveaux jeux de ligands, similaires aux porphyrines et aux BODIPY, ont été synthétisés. L’obtention et la caractérisation des complexes de ruthénium ainsi que leur réactivité par oxydation chimique ou électrochimique ont été réalisées. Pour les réactions de TAN, le mécanisme du dimère connu Rh2(esp)2 de type PCET (transfert couplé de proton et d’électron), semblable à celui des réactions par TAO, a été étudié en identifiant les différents intermédiaires formés grâce à une étude spectro-électrochimique. Ces différentes étapes ont ensuite été réalisées par voie photochimique développant ainsi l’utilisation de l’énergie lumineuse pour réaliser des réactions de TAO et TAN de manière éco-compatible. / Processes of oxidation and amination hold an important place on an industrial level but the current available methods are polluting and non-sustainable. To perform these transformations in the contour of green catalysis, bio-inspired oxygen atom transfer (OAT) and nitrogen atom transfer (NAT) reactions were addressed. In the case of OAT, the mechanism for the formation of the active species, the highly oxidized metal-oxo, is rather well described, and the challenge relies in the design of ligands to stabilize such species. For NAT, this step is less studied which limits the development of new catalysts. An even more challenging task resides in the use of light energy to generate these active species in the perspective to replace the classic oxidants. During this thesis, two projects have been undertaken. Firstly, the synthesis of dipyrrin based ligands and the corresponding ruthenium complex was evaluated for their ability to perform OAT reactions using conventional oxidants or the electrochemical way. Regarding the NAT reactions, we have investigated on the electrochemical, chemical and photochemical activation of the known catalyst Rh2(esp)2. Our strategy consisted in the activation of the nitrogen atom donor substrate, the sulfonamidate, in the coordination sphere of the catalyst. We disclose the spectroscopic signatures for the stepwise activation of the catalyst-substrate form. This work has as objective to set us on the path to develop a sustainable way to perform these reactions.

Anticancer active metal complexes such as cisplatin are routinely used for treating various cancers since 1978. However, the side effects of cisplatin overwhelm its therapeutic potential, especially in the latter stages of treatment. The nonspecific cytotoxicity of drugs could be avoided if targeted delivery to cancer cells is achieved using two different methodologies namely, enhanced permeability and retention in solid tumors (EPR) and receptor mediated endocytosis using a homing agent (RME). Ru(II)-arene complexes which are delivered specifically into cancer cells by the transferrin enzyme are less toxic compared to other metal complexes. The thesis describes the synthesis and use of Ru(II)-η6cymene complexes with different ancillary ligands which modulates the anticancer activity and the utility of two macromolecular vehicles in directed drug delivery. Ru(II)-η6cymene complexes with different heterocyclic ancillary ligands are synthesized and their anticancer activity tested against various cancer cell lines. Ruthenium complexes with mercaptobenzothiazoles are found to be quite active against the H460 cell lines that overexpress transferrin receptors and non-cytotoxic to the normal cell line, HEL299. Biophysical studies show that complexes (H1 and H8) can unwind the pBR322 DNA and inhibit the Topo IIα enzyme. A unique biphasic melting curve of CT DNA is observed in the presence of H1 which is attributed to formation of a dinuclear species (H20). Half-sandwich complexes of 6-thioguanine (6-TG) have also been prepared to improve the delivery and efficacy of 6-TG which is used in spite of a deleterious photoreaction. The Ru complexes cytotoxic to several leukemia cell lines. As they are photostable and anticancer active, they are better than 6-TG. Anticancer activity exhibiting piazselenols are used as ancillary ligands to make Ru(II)-arene complexes. Unfortunately, 1H NMR spectra suggests that piazselenol complexes dissociate in solution. However, the nitro substituted piazselenol and its Ru complex show the greatest cytotoxicity (<0.1 µM) against the A2780 cell line. The utility of PAMAM dendrimers and hyper branched polymers (hybramers) conjugated with a homing agent to target cancer cells by EPR and RME is probed. A cytotoxic copper complex (CuATSM) is covalently attached to the macromolecules through a disulfide linker, cleaved in the presence of GSH. Targeting efficacy of the folic acid-dendrimer conjugates is checked against two glioma cell lines. The folic acid-dendrimer conjugate is more active compared to dendrimer conjugate without folic acid against folate-receptor-overexpressing LN18 cell line. Biotin conjugated dendrimer shows better accumulation in HeLa cells, which require high amounts of biotin for growth. In vivo studies demonstrate that the conjugate can cross the blood-brain barrier. These studies suggest that PAMAM dendrimer can be used as a targeted delivery vehicle for cytotoxic metal complexes. Hyperbranched polymers decorated with propargyl groups and hydrophilic OH terminated TEG groups are attached to biotin and a cytotoxic Cu complex. (CuATSM-SS-CONH-N3) through ‘click’ reactions and tested against the HeLa cell line. On the basis of the studies conducted, it is concluded that targeted delivery of cytotoxic metal complexes are possible in the case of Ru(II) half-sandwich complexes and macromolecular vehicles like dendrimers are suitable for specifically delivering copper complexes into cancer cells.