Na primeira etapa deste trabalho foram sintetizados novos ligantes do tipo N-piridínicos, derivatizados de cadeias de ácidos graxos, a partir dos óleos vegetais de babaçu e canola in natura, aqui denominados ligantes Graxo-Amida (GA). Estes foram caracterizados por espectroscopia na região de infravermelho (IV) e ressonância magnética nuclear de hidrogênio e carbono (RMN 1H e 13C). Os ligantes foram coordenados a centros de rutênio do tipo cis-[RuCl2(LL)2] onde LL = 2,2\'-bipiridina, em que os ligantes cloro foram substituídos por duas unidades do ligante Graxo-Amida. Os íons complexos obtidos do tipo [Ru(bpy)2(GA)2]2+ foram caracterizados por análise elementar (CHN), IV, voltametria cíclica, espectroscopias eletrônicas de absorção e emissão e RMN (1H e 13C). Os voltamogramas obtidos mostraram uma diferença de potencial redox entre o complexo sintetizado com o óleo de canola e o sintetizado com o óleo de babaçu, ao comparar esses resultados com estudos voltamétricos da literatura do íon complexo [Ru(bpy)2(3-Amnpy)2]2+. Observou-se que a composição de ácidos graxos desses óleos vegetais, onde a presença ou não de insaturações, pode influenciar nas propriedades eletrônicas das espécies. O composto mostrou-se estável a presença luz, e não sofreu fotoquímica. A influência do meio em solução foi verificada e os indícios demonstram que os complexos não sofrem solvatocromismo. Os complexos possuem emissão em ~700 nm a 25°C quando excitados em λ480. Numa segunda etapa, monômeros de olefina cíclica do tipo ácido-norborneno foram inseridos nas cadeias de éster metílico, obtidas através da transesterificação do óleo de canola. Essa inserção foi realizada através de anéis oxiranos gerados nas insaturações das cadeias do éster. Reações de polimerização via ROMP foram realizadas com précatalisadores do Grupo, e estes monômeros mostraram alguma atividade frente à polimerização. / In the first stage of this work new N-pyridinic kind of ligands were synthesized, as fatty acids chain derivatized, from babaçu and canola vegetable oils, called fatty-amide ligands (GA). They were characterized by infrared spectroscopy (IR) and hydrogen and carbon nuclear magnetic resonance (1H and 13C NMR). The ligands were coordinated to cis-[RuCl2(LL)2] ruthenium center kind, where LL = 2,2\'-bipyridine, in which chlorine ligands where replaced by two fatty-amide ligand units. The obtained [Ru(bpy)2(GA)2]2+ complex kind were characterized by elemental analysis (CHN), IR, cyclic voltammetry, electronic absorption and emission spectroscopy and 1H and 13C NMR. The obtained voltammograms showed redox potential difference between the canola oil synthesized complex and the babaçu oil synthesized complex, when compared to the complex ion [Ru(bpy)2(3-Amnpy)2]2+ voltammetrics studies present in literature. It was observed that the vegetable oil fatty acids composition, in terms of insaturations presence or absence, have electronic influence on the species. The compound was stable at presence of light and suffered no photochemistry. The solution solvent was verified and there were no signs of solvatochromism. The complexes exhibited ~700 nm emission at 25 °C. In a second stage, norbonene acid cyclic olefin monomers kind were inserted in the methylic ester chains, obtained through canola oil transesterification. ROMP polymerization reactions were performed with our research group\'s precatalyst and these monomers showed some activity due to the polymerization.

Alors que les besoins en énergie de nos sociétés modernes ne cessent de croître, et que la prise en compte des enjeux environnementaux occupe une place de plus en plus importante dans le développement de nouvelles technologies, la mise au point de procédés de production d’hydrogène utilisant des ressources renouvelables, telles que le rayonnement solaire comme source d'énergie ou l’eau comme donneur d’électrons et de protons, est un enjeu de toute première nécessité. Ce travail de thèse s’inscrit dans la continuité des études menées au sein de l’équipe « SolHyCat » du Laboratoire de Chimie et Biologie des Métaux sur le développement de systèmes électro- et photocatalytiques pour la réduction des protons en H2. Dans cette perspective, nous avons ainsi contribué à l’élaboration d’une photocathode moléculaire de production de H2 à travers la compréhension de différents paramètres moléculaires relatifs à sa construction. Dans un premier temps, nous nous sommes intéressés à la construction d’un lien covalent entre un motif photosensibilisateur et un centre catalytique de réduction des protons via la synthèse de dyades modèles. En parallèle, nous avons développé une méthodologie de synthèse permettant l’introduction de groupements d’ancrage robustes dans la sphère de coordination de photosensibilisateurs métallo-organiques. Enfin, l'étude des propriétés électrochimiques d'une nouvelle série de catalyseurs de réduction des protons à sphère de coordination polypyridinique a été étudiée. / There is an urgent need to provide solutions for the energetic challenge our planet has to face. The production of “environmentally friendly” fuels such as dihydrogen H2 through sunlight-driven water splitting holds great promise. Hydrogen is indeed a carbon-free energy carrier that can be stored and used on request to produce electricity thanks to the mature fuel cell technology. Moreover, water and solar energy form the ideal couple for H2 production because they are both readily available and their use is considered to be safe for the environment. The design and study of molecular photocatalytic systems for H2 evolution from water has therefore been the subject of intensive research interest in the last decade and their implementation into functional dye-sensitized photoelectrocatalytic cells recently appeared in the literature. It is nevertheless necessary to optimize the efficiency of these molecular systems in order to reach the targeted solar-to-hydrogen conversion yield. In that context, this PhD thesis aimed at getting a better understanding of parameters relevant for the optimization of molecular H2-evolving photocathodes: first, different coupling strategies have been studied to covalently assemble a light-harvesting unit with a redox-active moiety; second, a synthetic methodology allowing introduction of robust anchoring groups in the coordination sphere of ruthenium photosensitizers has been widely studied and the first photoelectrodes characterized; finally, a new series of proton reduction catalysts featuring a polypyridinic ligand has been investigated, allowing important kinetic and mechanistic insights to be obtained.

No description available.

Flavonols are hydroxyl-substituted flavonoids and naturally occur as secondary metabolites in plants. Several studies have discovered extensive medicinal properties of flavonols. The present work reports on structural and functional investigation of the B ring substituted flavonols based on spectroscopic and electrochemical techniques. The purpose of this study is to determine the influence of the B ring substitutions on the hydrogen bonding interactions, the electronic effects in ruthenium complexes and the Al3+ chelation of B ring substituted flavonols. The electronic effects of the B rings were changed by introducing methyl, methoxy and nitro groups at position 4ʹ on the B ring. The 3ʹ-methyl substitution was performed in order to increase the electronic density of the B ring via inductive effects. The 2ʹ-methyl and 2ʹ, 6ʹ-dimethyl substitutions increased the steric effects around the inter-ring bond between the B and the C rings, and the B ring was highly deconjugated from the AC rings. The intramolecular hydrogen bonding distances at 3-hydroxy-4-carbonyl units of the B ring substituted flavonols were elongated while the dihedral angles between the B and AC increased. Strong intermolecular hydrogen bonding interactions were also observed in the crystal structures of 4ʹ-methylflavonol, 4ʹ-methoxyflavonol, 4ʹ-nitroflavonol and 2ʹ,6ʹ-dimethylflavonol. Furthermore, several crystal packing patterns were observed, and it is postulated that dihedral angles and intramolecular hydrogen bonding distances are both affected by the intermolecular hydrogen bonding interactions and the crystal packing forces. In addition, the ruthenium complexes of B ring substituted flavonols were synthesized and characterized by spectroscopic and electrochemical techniques. B ring substitution effects were minimal in IR spectroscopy and X-ray crystallography. The levels of the conjugation of the rutheniumlavonolate complexes were demonstrated by electronic absorption spectra recorded in methanol at room temperature. The most positive oxidation potential was obtained with the electron withdrawing nitro group substitution, and the electron donating substitutions resulted in more negative oxidation potentials. The spectroscopic investigation of the complex formation of Al(III) with flavonols and 3-hydroxychromone is described. The stoichiometric composition and stability constants are also given. The comparison of the results obtained from Al(III) chelation shows significant effects of the B ring substitutions.

yes / The complexes [RuCp*(PP)Cl] (Cp* = C5Me5; [1], PP = dppm; [4], PP = Xantphos), [RuCp#(PP)Cl] (Cp# = C5Me4(CH2)5OH; [2], PP = dppm; [5], PP = Xantphos) and [RuCp*(dppm)(CH3CN)][SbF6] [3] were synthesized and evaluated in vitro as anticancer agents. Compounds 1–3 gave nanomolar IC50 values against normoxic A2780 and HT-29 cell lines, and were also tested against hypoxic HT-29 cells, maintaining their high activity. Complex 3 yielded an IC50 value of 0.55 ± 0.03 μM under a 0.1% O2 concentration.

Yes / The synthesis of nanoparticles of conjugates of caffeic acid-modified chitosan with ruthenium arene complexes is described. The chemical structure and physical properties of the nanoparticles were characterised by electronic absorption spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR), 1H NMR spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray powder diffraction (XRD), and circular dichroism (CD) analysis. The multi-spectral results revealed that caffeic acid is covalently bound to chitosan and chelates to {Ru(p-cymene)Cl}+. The DLS studies indicated that the Ru–caffeic acid modified chitosan nanoparticles are well-defined and of nanometre size. Such well-defined nanocomposites of chitosan and metal complexes might find a range of applications, for example in drug delivery. / We thank the National Natural Science Foundation of China (Project No. 21571154), the Jiangsu Overseas Research & Training Program for University Prominent Young & Middle-aged Teachers and Presidents, Leverhulme Trust (Early Career Fellowship No. ECF-2013-414 to NPEB), the ERC (Grant No. 247450 to PJS), EPSRC (EP/F034210/1 to PJS) and Science City (AWM/ERDF) for support, and EU COST Action CM1105 for stimulating discussions.

No description available.

The thesis “Ancillary Ligand Effects on the Anticancer Activity of Ruthenium (II) Piano Stool Complexes” is an effort to design better antitumor metallodrugs based on ruthenium(II) complexes with various H-bond donor/acceptor ligands and to understand their mechanism of action. Chapter 1 presents a brief review of metallodrugs and their mechanism of action. Different classes of metallodrugs are discussed. A short discussion on ruthenium based anticancer drugs and their established mechanism of action is also included in this chapter. Chapter 2 deals with the synthesis, characterization and anticancer activity of Ru(II) complexes with P(III) and P(V) ligands. The effect of a strong hydrogen bond acceptor on the cytotoxicity of the complexes has been investigated which allows comparison of complexes with ligands possessing a strong hydrogen bond donor or hydrogen bond acceptor. Partial oxidation of the tertiary phosphine ligands leads to a decrease in cytotoxicity of the ligand, while coordination to ruthenium resulted in a significant increase in the cytotoxicity. A molecular mechanism of action for these complexes was suggested on the basis of various biophysical studies. These complexes bind DNA through non-intercalative interactions which lead to the destabilization of the double helix of the DNA and also unwinding of the negatively supercoiled DNA. Results show that the presence of a hydrogen bond acceptor on the ligand is not capable of enhancing interactions with DNA in comparison with hydrogen bond donor groups. Cellular studies of these complexes showed that inhibition of DNA synthesis and apoptosis occur on treatment with these complexes. Interestingly, these complexes are found to be not only cytotoxic but also antimetastatic. Chapter 3 deals with the synthesis, characterization and anticancer activity of Ru(II) complexes with biologically active S containing heterocyclic ligands and their mechanistic study. Complexation of ruthenium with mercaptobenzothiazole (MBT) gave the most cytotoxic complex (H3) in the series. Heterocyclic Ru(II) complexes behave differently as evidenced by cellular and biophysical studies. Unlike phosphine complexes, H3 shows biphasic melting of DNA at higher concentrations which suggests two different types of interaction with DNA. Chapter 4 deals with synthesis and characterization of water soluble multiruthenated hydrophilic ruthenium(II) complexes with urotropine. An increase in cytotoxicity and binding affinity has been observed with increase in the number of ruthenium atoms per molecule. The complex with three ruthenium atoms showed the best activity. However cytotoxicity of the complexes decreases with decrease in the lipophilicity of the complexes. Chapter 5 describes studies on the interaction of Ru complexes with water, ss-DNA, AMP, GMP and GSH by various spectroscopic techniques. Hydrolysis of Ru-Cl bond in the complexes correlates with the cytotoxicity. Chapter 6 reports the summary of the observations of the thesis and the future prospects of metallodrugs.

Através da abordagem bottom-up, foram desenvolvidos novos sistemas supramoleculares baseados em complexos metálicos ligados por meio do ligante conjugado, trans-1,4-bis[2-(4-piridil)etenil]benzeno (BPEB). A combinação adequada de várias espécies selecionadas, conduziu a compostos bastante interessantes que foram caracterizados por meio 1H-RNM, voltametria cíclica e de espectrometria de massa, espectroscopia eletrônica, espectroeletroquímica. Seus correspondentes filmes moleculares também foram investigados por meio de microscopia de força atômica. Um desses sistemas foi constituído por clusters triangulares de acetato de rutênio com pontes µ-oxo e BPEB. Nesses casos, a espectrometria de massa acoplada à técnica de dissociação induzida por colisão, foi uma ferramenta poderosa para a investigação do processo de fragmentação em fase gasosa, permitindo a caracterização de novos intermediários, bem como a avaliação das energias de ligação envolvidas nos sistemas. Uma correlação linear das energias de ligação e parâmetros eletroquímicos foi demonstrada neste trabalho. Além disso, o comportamento eletrocrômico dos clusters de BPEB suportados sobre dióxido de titânio nanocristalino, também foi explorado na elaboração de dispositivos eletrocrômicos, com ótimo desempenho em termos de mudanças ópticas, reversibilidade e reprodutibilidade. Outro tipo de sistema foi baseado em complexos de rutênio-bipiridina e BPEB. Esses complexos foram empregados com bons resultados como sensibilizadores em células fotoeletroquímicas baseadas em dióxido de titânio nanocristalino, bem como em dispositivos eletrocrômicos de mesma natureza. Finalmente, as características estruturais do BPEB mostraram ser adequadas para exploração do reconhecimento molecular dos complexos na presença de β-ciclodextrina (β-CD). Neste estudo, foram gerados rotaxanos por meio da automontagem coordenativa do complexo binuclear µ-BPEB- bis[pentacianoferrato(II)] na presença de β-CD. Também foi demonstrado por meio de 1H-NMR, que a agregação do complexo de BPEB é bastante pronunciada em espectros de solução aquosa, sendo porém inibida na presença de β-CD. / The bottom up approach has been applied for the development of new supramolecular systems based on metal complexes connected by the linear, conjugated bridging ligand trans-1,4-bis[2-(4-pyridyl)ethenyl]benzene (BPEB). The combination of the many selected species led to very interesting compounds, which have been extensively characterized by means of ESI-MS, electronic spectroscopy, 1H-NMR, cyclic voltammetry and spectroelectrochemistry. Their molecular films have also been investigated by means of atomic force microscopy. One of such systems was constituted by triangular µ-oxo bridged ruthenium acetate clusters containing BPEB. In particular, mass spectrometry coupled with a collision induced dissociation technique provided a versatile tool for the investigation of their fragmentation process, allowing the characterization of novel intermediates, as well as, the evaluation of the binding energies involved in the systems. A linear correlation of the binding energies and electrochemical parameters has also been demonstrated in this work. In addition, the electrochromic behavior of the cluster-BPEB complexes supported on nanocrystalline titanium dioxide has also been exploited for the design of novel electrochromic devices, exhibiting sharp optical changes, high reversibility and great reproducibility. Another interesting type of system was based on polypyridine ruthenium(II) complexes and BPEB. Such species have been successfully employed as sensitizers in nanocrystalline titanium dioxide photoelectrochemical cells, and in photoelectrochromic devices. Finally, the suitable structural characteristics of BPEB have been explored in molecular recognition processes involving the corresponding complexes in the presence of ß-cyclodextrin (ß-CD). In this study, rotaxanes have been generated by coordination self-assembly of the binuclear µ-BPEB- bis[pentacyanoferrate(II)] complex and ß-CD. It has also been shown that the aggregation of the BPEB complexes, which proceeds to a high extent in aqueous solution, can be inhibited by adding ß-CD, as deduced by means of 1H-NMR spectroscopy

O NO é uma molécula endógena, envolvida em numerosos processos fisiológicos e patológicos. Diversas substâncias capazes de liberar NO in vivo têm sido estudadas, incluindo os complexos nitrosilo de rutênio, como o [Ru(terpy)(bdqi-COOH)NO](PF6)3, capaz de liberar NO após fotoestímulo. Considerando que as funções específicas do NO dependem de sua localização e cinética de liberação, e que a sua aplicação tópica pode evitar possíveis efeitos colaterais, o objetivo deste trabalho foi estudar a absorção cutânea passiva e iontoforética do complexo [Ru(bdqi-COOH)(terpy)(NO)](PF6)3, assim como a do NO dele liberado. A atividade citotóxica do complexo também foi estudada em cultura de células tumorais A431 na presença e ausência de luz e de corrente elétrica. Foi desenvolvido e validado um método analítico para a quantificação do complexo de rutênio por CLAE e estudos de pré-formulação de solubilidade, coeficiente de partilha e estabilidade do complexo foram realizados antes dos estudos de penetração cutânea. O complexo de rutênio manteve-se estável em solução aquosa a temperatura ambiente até o período de 48h, mas instável em contato com a pele inteira, com a degradação de 61% após 8h. Em contato apenas com o estrato córneo (EC), no entanto, a degradação do complexo não foi considerada significativa após 4 h. A aplicação de uma corrente elétrica fraca a uma solução do complexo em pH fisiológico não alterou a estabilidade do mesmo, que não apresentou degradação significativa por 6h. Nos estudos de penetração passiva, observou-se por CLAE e por espectrometria de massas com fonte de plasma acoplado (ICP-MS) que o complexo foi capaz de penetrar o EC sem sofrer degradação, mas liberando parte do NO quando em contato com a epiderme viável. A aplicação da iontoforese aumentou significativamente a quantidade de rutênio na epiderme viável e solução receptora (6 e 15 vezes respectivamente), indicando maior penetração do complexo. O complexo Ru-NO assim como seu aquo complexo (formado após liberação do NO), não apresentaram citotoxicidade às células A431, na ausência de luz. A irradiação das células incubadas com o complexo, passivamente, em 377 e 532nm com diferentes doses também não acarretou morte celular significativa. No entanto, a aplicação de corrente elétrica constante (0,3mA cm-2) seguida de incubação por 4h com o complexo levou a morte celular de aproximadamente 50% das células A431 após irradiação em 377 nm com a dose de 10J cm-2. Para atingir este mesmo resultado com a irradiação em 532nm foi necessário aumentar o tempo de incubação com o complexo para 24h. Conclui-se, resumidamente, que a corrente elétrica aumentou a entrada do complexo na pele e nas células, levando a liberação de maior quantidade de NO dentro delas, com consequente morte celular. A liberação do NO do complexo estudado ocorre não apenas por estímulo luminoso mas também por reações de oxi-redução quando em contato com a pele ou com a cultura de células estudadas. Sendo assim, propõe-se a encapsulação deste complexo em sistemas de liberação com o intuito de controlar a liberação do NO. Experimentos preliminares de nanopartículas contendo o complexo estão descritos no Apêndice 1 desta tese. / NO is an endogenous molecule that is involved in numerous physiological and pathological processes. Several compounds capable of releasing NO in vivo have been studied, including nitrosyl ruthenium complexes such as the [Ru (terpy)(bdqi-COOH)NO](PF6)3 that is capable of releasing NO after photo-stimulus. Because the specific role of NO depends on its location and kinetics of release, and its topical application may avoid possible side effects, the aim of this work was to study the passive and the iontophoretic skin absorption of the [Ru(terpy)(bdqi-COOH)NO](PF6)3 complex, as well as its NO release. The cytotoxic activity of the complex was also studied in A431 tumor cells in the presence and absence of light and electrical current. An analytical method for the quantification of the ruthenium complex by HPLC was developed and validated; studies of pre-formulation such as solubility, partition coefficient and stability of the complex were also performed before the penetration studies. The ruthenium complex was stable in aqueous solution at room temperature for 48 hours, but unstable in contact with the full-thickness skin (61% was degraded after 8 h). However, the complexs contact for 4 h with the stratum corneum (SC) alone did not lead to the complex degradation. The application of a weak electric current in a solution of the complex at physiological pH did not affect its stability, which showed no significant degradation for 6 h. In the passive penetration studies it was observed, by HPLC and inductively coupled plasma-mass spectrometry (ICP-MS), that the complex was able to penetrate the SC without degradation, but with some NO release when in contact with the epidermis. The application of iontophoresis significantly increased the amount of ruthenium in the viable epidermis and in the receiver solution (6 and 15 times, respectively), indicating greater complex penetration. The nitrosyl ruthenium complex and its aquo complex (formed after release of NO) showed no cytotoxicity to A431 cells in the absence of light. The irradiation of the cells incubated with the complex, passively, in 377 and 532 nm with different doses also did not cause significant cell death. However, the application of a constant electric current (0.3 mA cm-2) for 30 min followed by incubation for 4 h with the complex led to approximately 50% of A431 cell death after irradiation at 377 nm with a dose of 10J cm-2. To achieve this same result with irradiation at 532 nm it was necessary to increase the incubation time with the complex for 24 hours. In summary, the electric current increased the nitrosyl ruthenium complex skin and cell penetration, leading to release of higher amounts of NO into them, with consequent cell death. Furthermore, the release of NO from the ruthenium complex is showed to happen not only by light stimuli but also by redox reactions when it is in contact with the skin or with the culture of cells studied. Therefore, we propose the encapsulation of this complex in delivery systems in order to control the release of NO. Preliminary experiments with nanoparticles containing the complex are described in Appendix 1.