Compostos do tipo [M2(O2CR)4] com ligação múltipla direta entre os centros metálicos apresentam importância do ponto de vista teórico bem como da química aplicada a diversas áreas. Recentemente tem havido um grande interesse voltado, especialmente, para o design de novos materiais construídos com base nestas unidades dimetálicas. O principal objetivo deste trabalho é o estudo de complexos de rutênio que apresentam núcleos M2 de valência mista do tipo Ru2(lI,III) com ligantes dicarboxílicos. A partir do complexo [Ru2(OAc)4CI], foram sintetizados compostos com os ligantes dicarboxilatos -O2C-R-CO2-, em que R são cadeias carbônicas saturadas (succinato, adipato e dodecanodioato) ou anéis aromáticos (tereftalato e 4,4\'-bifenildicarboxilato). Modificando-se a metodologia de síntese, foi possível isolar dois tipos de compostos: [Ru2(O2C-R-CO2)2CI] (R = succ, adip, dode, tere e bife) e [Ru4(O2C-R-CO2)5(H2O) 2] (R = adip e dode). Todos os compostos apresentam bandas de absorção na região do visível, ao redor de 450 nm, e do infravermelho próximo, ao redor de 1100 nm, que podem ser atribuídas, respectivamente às transições eletrônicas π (Ru-O, Ru2) → π* (Ru2) e δ (Ru2) → δ* (Ru2). Estas transições são características de espécies de [Ru2]5+, comprovando a manutenção das ligações metal-metal nos derivados. Os valores dos momentos magnéticos efetivos (µeff), calculados com base em medidas de susceptibilidade magnética, estão na faixa de 3,8-4,4 M.B para os compostos [Ru2(O2C-R-CO2)2CI] (R = succ, adip e dode) e correspondem à configuração eletrônica do estado fundamental do tipo σ2 µ4 δ2 (µ*)2 (δ *)1, com três elétrons desemparelhados, que é observada para carboxilatos de dirutênio (lI,III). Valores de µeff um pouco mais altos foram obtidos para os demais compostos, provavelmente devido à existência de algum tipo de acoplamento magnético. Nos espectros vibracionais FT-IR, observam-se bandas na faixa de 1470 a 1390 cm-1, que é típica das frequências de estiramentos νa e νs dos grupos COO- de carboxilatos ligados em ponte. Bandas relativas às frequências de estiramento das ligações metal-metal, ν(Ru-Ru), são observadas nos espectros Raman ao redor de 330 cm-1. Estes dados indicam que os compostos apresentam estruturas do tipo gaiola em que os ligantes carboxilatos formam pontes equatoriais (via grupo COO-) entre dois íons metálicos, estabilizando a ligação múltipla Ru-Ru. Devido à presença de dois grupos COO- para cada íon dicarboxilato, ocorre também a formação de pontes equatoriais entre centros de [Ru2]5+, gerando espécies poliméricas constituídas por unidades [Ru2(O2C-R-CO2)2]+. As posições axiais são ocupadas pelos ânions cloreto ou carboxilato, respectivamente nos casos dos compostos [Ru2(O2C-R-CO2)2CI] e [Ru4(O2C-R-CO2)5(H2O)2], que também formam pontes entre unidades dimetálicas. As presenças das pontes axiais e das pontes equatoriais entre unidades de [Ru2]5+ gerando estruturas tridimensionais que apresentam dois tipos distintos de lamelas ou camadas foram comprovadas com base nos valores das distâncias interplanares calculadas a partir dos difratogramas de raios-X de pó dos compostos. Os compostos são termicamente estáveis até a temperatura de ~ 250°C, conforme verificado por meio de estudos de análise termogravimétrica. Acima desta temperatura, começam a ocorrer perdas de massa que correspondem às perdas totais dos ligantes equatoriais e axiais, considerando-se o RuO2 como produto final das decomposições térmicas. Os compostos [Ru2(adip)2CI], [Ru2(tere)2CI] e [Ru4(dode)5(H2O)2] apresentam áreas superficiais elevadas, aproximadamente iguais a 170, 100 e 40 m2/g, respectivamente, que podem estar relacionadas à formação de estruturas microporosas. Estes tipos de estruturas com poros podem atuar como adsorvedores de gases, por exemplo, o que torna os compostos bastante promissores para aplicação na área de novos materiais microporosos, especialmente o primeiro cuja área é cerca de duas vezes maior do que a do segundo, o qual está descrito na literatura como bom adsorvedor para N2, O2 e Ar. / Compounds containing dimetal units [M2(O2CR)4] which have metal-metal multiple bonds are of great interest in both theoretical and applied chemistry. Recently they have been investigated as important compounds for the design of new materiaIs. The main goal of this work is the study of mixed valent diruthenium carboxylates. Compounds formed by Ru2(II,III) centers and -O2C-R-CO2- dicarboxylate ligands, where R is a saturated carbon chain (succinate, adipate and dodecanodioate) or aromatic ring (terephthalate and 4,4\'-diphenyldicarboxylate), were synthesized. Two types of compounds were obtained depending on the synthetic methodology: [Ru2( O2C-R-CO2)2CI] (R = succ, adip, dode, tere and bife) and [Ru4(O2C-R-CO2)5(H2O) 2] (R = adip and dode). AlI compounds exhibit absorption bands in the visible region, around 450 nm, and in the near infrared, around 1100 nm, which can be ascribed respectively to the π (Ru-O, Ru2) → π* (Ru2) and δ (Ru2) → δ* (Ru2) electronic transitions. These are characteristic of [Ru2]5+ dimetal species, indicating that the metal-metal bonds are present in the derivatives. The effective magnetic moments (µeff) values calculated from magnetic susceptibilities data are in the range of 3.8 - 4.4 B.M. for the [Ru2(O2C-R-CO2)2CI] (R = succ, adip and dode) compounds, corresponding to the σ2 µ4 δ2 (µ*)2 (δ *)1 ground state electronic configuration, with three unpaired electrons, that is observed for diruthenium (II,III) carboxylates. Higher µeff values found for the other compounds can be due to some type of magnetic coupling. The FT-IR vibrational spectra show characteristic bands in the region of 1470 1390 cm-1 that is typical of symmetric and asymmetric bridging carboxylate stretching modes. The metal-metal stretching modes, ν (Ru-Ru), are observed in the Raman spectra around 330 cm-1. Based on these results, it can be proposed that the compounds exhibit \'lantern\' type structures where the carboxylate ligands bridge two metal ions equatorially by COO- groups, stabilizing the Ru-Ru multiple bound. Due to the presence of two COO- groups for each dicarboxylate ion, there is the occurrence of equatorial bridges between [Ru2]5+ centers too, generating polymeric species constituted by [Ru2(O2C-R-CO2)2]+ units. The chloride or the carboxylate anionic axial ligands, respectively in [Ru2(O2C-R-CO2)2CI] and [Ru4(O2C-R-CO2)5(H2O)2] compounds, can also bridge the dimetal units in the axial direction. The existence of these axial and equatorial bridges between [Ru2]5+ units generate tridimensional network structures that exhibit two different types of layers, as shown by the analysis of the interplanar distances calculated from powder X-ray diffiaction of the solids. The compounds are thermally stable up to 250°C as indicated by thermogravimetric analysis. Above this temperature, there are losses of mass that correspond to the total losses of the equatorial and the axial ligands considering the RuO2 as the product of thermal decomposition. The [Ru2(adip)2CI], [Ru2(tere)2CI] and [Ru4(dode)5(H2O)2] compounds exhibit large superficial areas, about 170, 100 and 40 m2/g respectively, which could be indicative of microporous structures. These kinds of porous structures can be used as adsorbents for gases, for example. It makes the compounds very interesting for application as new microporous materiaIs, specially for the former which has a superficial area twice as bigger as the second one that is described in the literature as good adsorbent for N2, O2e Ar.

Protein phosphorylation is a post translational modification of proteins in which a serine, a threonine or a tyrosine residue is phosphorylated by an enzyme, kinase. Phosphorylation of proteins is a reversible and very important regulatory mechanism that occurs in both prokaryotes and eukaryotes. Phosphorylation turns many protein enzymes on and off, preventing or causing many diseases such as diabetes, cancer and rheumatoid arthritis. The phosphorylation on tyrosine residues of proteins is essential for transmission of signals for cell growth, proliferation and differentiation. Protein tyrosine phosphatases (PTPs) in concert with protein tyrosine kinases (PTKs) regulate many signal transduction pathways by controlling the degree of phosphorylation of tyrosine residues within the protein. While the roles and mechanisms of protein tyrosine kinases are well documented, our present understanding of protein tyrosine phosphatases is very limited. In this regard we still have much more to learn about PTPs. Here we propose the design and synthesis of novel protein tyrosine phosphatase mimetics and their activity against tyrosine phosphatases. Chapter two describes the synthesis of 2-aminopyrimidine chlorides, sulfonamides and the sequence of reactions to make its amino acid analog. Chapter three describes the synthesis of α-aryl, α,β-epoxy carboxylates, phosphonates and their biological activity against tyrosine phosphatases. These compounds could be very helpful in significantly improving the current understandings about the roles and mechanisms of the PTPs. These proposed tyrosine phosphatase inhibitors are believed to work effectively in treating the diseases by modulating the phosphorylation in signal transductions pathways. Chapter four describes the design and the synthesis of Peptide Nucleic Acids (PNAs) both standard as well as hybrid PNAs with novel cysteine based monomers that are aimed to increase the cellular uptake by introducing positively charged or amphipathic species attached to cysteine thiol functional group.

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No description available.

The present thesis provides a systematic investigation of coordination polymers of 3d, rare-earth (4f) and main group element (Bi) using both rigid aromatic, flexible aliphatic linkers. Luminescent sensing behavior towards nitro aromatics, metal ions and ferroelectric behavior have been investigated using some of the prepared compounds. The possible usefulness of lone pair on the structure has been investigated using bismuth based coordination polymers. The thermal and optical behavior of lanthanide coordination polymers (Ce, Pr and Nd) have also been studied. Chapter 1 An Overview of Coordination Polymer (CP) Compounds This chapter presents a brief introduction to coordination polymer (CP) compounds. Starting from the brief historical background on coordination compounds, this chapter shed light on some earlier developments in this family of compounds by Yaghi, Robson and others. The usefulness of carboxylate and imidazolates in construction of some important coordination polymer compounds like MOF-5, HKUST-1, ZIFs, MIL-53, UiO-66, CD-MOF-1 etc has been described in detail along with its properties. The coordination polymers exhibit many important properties and some of the properties like sorption, separation, ionic conductivity, catalysis and ferroelectricity have been discussed briefly and summerized. Chapter 1 also provides the general synthetic and characterization approaches that have been employed during the present studies. Chapter 2 Part A: Adenine Based Coordination Polymers with Cyclohexane dicarboxylic acids This chapter presents the synthesis, structure and properties of four new coordination polymers [Zn4(C8H10O4)2.5(C5H4N5)3.2H2O].7H2O.2DMA (I), [Cd3(C8H10O4)2(C5H4N5)2.H2O] (II), [Cd(C8H11O4)2(C5H5N5)2.2H2O] (III), [Cd(C8H10O4)(C7H8N5O).H2O]. 4H2O (IV), (CHDA = cyclohexane dicarboxylic acid, ad = adenine, DMA = dimethylacetamide, 9-HEA = 9-hydroxyethyl adenine). The compound I and II forms three-dimensional structure having distinct arrangements of 1,4-CHDA and adenine units with Zn and Cd metals respectively. The molecular complex unit is observed in compound III with 1,2-CHDA and adenine. Compound IV forms two-dimensional structure with 9-HEA and 1,2-CHDA. The observation of base-pairing interactions in the above compounds is noteworthy. In compounds I, II and IV amino groups are appears to be free and utilized for the detection of nitro aromatic explosives through fluorescence quenching. The results revealed that the emission behavior of the present compounds is greatly influenced by the hydroxyl nitroaromatic analyses like indophenol, dinitrophenyl and trinitrophenols with very low detection limits. The compound I also exhibits considerable sensitivity towards metal ion detection, especially Fe2+/Fe3+, Cr3+, Ag+ and Hg2+ ions in solution. The presence of free nitrogen sites in compound II has been explored for the base catalyzed Knoevenagel condensation reaction, the quantitative yields are observed with various aldehyde substrates. Part B: Adenine Based Coordination Polymer with Oxydiacetic acid: [Cd2(C4H4O5)2(C5H5N5)].H2O.DMA The synthesis, structure and properties of a Cd based coordination polymer with oxydiacetic acid and adenine, [Cd2(C4H4O5)2(C5H5N5)].H2O. DMA is described. The compound has a two-dimensional structure formed by the connectivity involving Cd and oxydiacetic acid. The adenine ligand binds with the Cd metal center through the pyrimidine nitrogen and hangs in the inter layer spaces. The layers are stacked in a ABAB.... fashion and the inter layer spaces occupied by the dimethyl amine and water molecules. The water molecules are very labile and its removal can be accomplished by heating the sample at 100°C, which is also confirmed by the single crystal XRD, PXRD and IR studies. The availability of free amino groups of adenine molecule has been utilized for the detection of nitroaromatics, especially nitrophenols with good sensitivity. The amino group was also found to be useful in catalyzing Knoevenagel condensation reactions. Chapter 3: Rare-Earth Metal Carboxylates: Ln2(µ3-OH)(C4H4O5)2(C4H2O4)].2H2O [Ln=Ce, Pr and Nd] This chapter describes synthesis, structure and properties of series of rare-earth based compounds, [Ln2(µ3-OH)(C4H4O5)2(C4H2O4)].2H2O (Ln = Ce, Pr and Nd). The malic acid and fumaric acid form part of the structure. The lanthanide centers are connected by the malate units to form a two dimensional layers, which are pillared by fumarate units forming the three-dimensional structure. Overall, structure can be described as I2O1 type inorganic in two-dimension (Ln-O-Ln layers) and organic in one dimension. The extra framework water molecules form a dimer and occupy the channels. The robustness of the framework was reflected in terms of facile removal and reinsertion of the water molecules, which is also confirmed by single crystal XRD, variable temperature IR and cyclic TGA study. The presence of water dimers and weakly interacting water chain suggested the possibility of proton migration in these compounds. Proton conductivity studies reveal the conductivity values of ~2.85 x 10-6 Ω-1cm-1 at 98% relative humidity. The optical studies revealed an up-conversion behavior involving more than one photon for the neodymium compound. Chapter 4: Bismuth Carboxylates with Brucite and Fluorite Related Structures The synthesis, structure and properties of three new bismuth based coordination polymers have been described in this chapter. The compounds [C4N2H10][Bi(C7H4NO4)(C7H3NO4)].H2O (I), [Bi(C5H3N2O4) (C5H2N2O4)] (II) and [Bi(µ2-OH)(C7H3NO4)] (III) were isolated employing hydrothermal condition with three different heterocyclicdicarboxylic acids, 3,6-pyridinedicarboxylic acid, 4,5-imidazoledicarboxylic acid and 3,4-pyridinedicarboxylic acid respectively. The structures of all the compounds have linkages between Bi2O2 and the corresponding dicarboxylate forming a simple molecular unit in I, a bilayer arrangement in II and a three-dimensional extended structure in III. The topological arrangement of the nodal building units in the structures resembles brucite related layers in II and fluorite related arrangement in compound III. By utilizing the secondary interactions, the structure of III can be correlated to a Kagome related net. The observation of such classical inorganic related structures in the bismuth carboxylates is noteworthy. Heterogeneous catalytic studies indicate Lewis acidic nature in the bismuth center in all three compounds. Chapter 5: Solvent dependent Delamination, Restacking and Ferroelectric studies in a Two-Dimensional Compound [NH4][Ag3(C9H5NO4S)2(C13H14N2)2].8H2O This chapter describes synthesis, structure, water dependent delamination/restacking and ferroelectric behavior in a layered coordination polymer compound, [NH4][Ag3(C9H5NO4S)2(C13H14N2)2].8H2O. The compound has a two-dimensional structure with the water molecules occupying the inter-lamellar spaces. The lattice water molecules can be fully removed and reinserted, which accompany the crystalline-amorphous-crystalline transformation. This transformation resembles the collapse/delamination and re-stacking of the layers. This transformation has also been investigated by in-situ IR and PXRD studies. The presence of a natural dipole (anionic framework and cationic ammonium ions) along with the non-centrosymmetric space group gives rise to a room-temperature ferroelectric behavior to the compound with saturation polarization (Ps) of 1.95 μC/cm2 and remnant polarization of 0.63 μC/cm2. The temperature dependent dielectric measurements indicate that the ferroelectric-paraelectric transformation occurs at 320 K. The ferroelectric-paraelectric transformation also follows the crystalline-amorphous-crystalline transitions.

Reaction of BiPh3 or Bi(OtBu)3 with benzohydroxamic acid (H2-BHA) results in formation of novel mono- and di-anionic hydroxamato complexes; [Bi2(BHA)3]∞1, [Bi(H-BHA)3] 2, [Bi(BHA)(H-BHA)] 3, all of which display nM activity against Helicobacter pylori. Subsequent dissolution of [Bi2(BHA)3]∞ in DMSO/toluene results in hydrolysis to the first structurally authenticated {Bi34} oxido-cluster [Bi34O22(BHA)22(H-BHA)14(DMSO)6] 4. / Dieser Beitrag ist aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Neste trabalho uma classe de carboxilatos trinucleares de rutênio coordenados a ligantes ortometalados foi apresentada. As propriedades eletrônicas, eletroquímicas e fotofísicas destes complexos foram investigadas, bem como a atividade anticâncer e interações com biomoléculas alvo, DNA e HSA. Foram realizadas as sínteses e caracterização dos ligantes (L2) C18H10N4, (L3) C19H12N4, (L4) C18H9ClN4, dos precursores (1) [Ru3O(OAc)6(CH3OH)3]CH3COO, (2) [Ru3O(OAc)6(CO)(CH3OH)2], (3) [Ru3O(OAc)6(CO)(py)2], (4) [Ru3O(OAc)6(H2O)(py)2]PF6 e dos novos complexos (1-5), [Ru3O(OAc)5(py)2(L)]PF6, (onde py = piridina, L1 = dppn, L2 = dppz, L3 = dppzCH3, L4 = dppzCl, L5 = phen). Os dados de RMN mostraram que a ortometalação dos ligantes fenazínicos afeta a estrutura dos complexos, com severo abaixamento de simetria. Já a investigação das propriedades eletrônicas e eletroquímicas indicaram que a presença de diferentes substituintes e a basicidade dos ligantes ortometalados influenciaram pouco as propriedades da unidade [Ru3O]+. Em termos da estrutura eletrônica dos complexos, este efeito indica que não há interações de natureza significativas entre os orbitais da unidade [Ru3O]+ e dos ligantes ortometalados. Esse fato pode se originar na falta de planaridade entre a unidade [Ru3O]+ e os ligantes fenazínicos. Os resultados de citotoxicidade em linhagem de célula tumoral (B16F10) e não tumoral (L929) mostraram que os complexos apresentam efeito citotóxico maior contra as células tumorais do que os ligantes livres, bem como baixa citotoxicidade contra a célula não tumoral. Estes resultados mostraram que a série com ligantes ortometalados traz os exemplos com os melhores desempenhos já observados em nosso grupo de pesquisa, em comparação com outros clusters com ponte -oxo, frente ao câncer de melanoma. Os estudos de interação com biomoléculas alvo mostraram que os complexos interagem com o DNA e a HSA. Com o DNA observou-se interações de natureza eletrostática, com contribuição do mecanismo de intercalação à medida que o tamanho e a extensão da conjugação dos ligantes ortometalados aumentam, sendo que o processo de intercalação é favorecido no caso do complexo (1) com o ligante dppn. Foram realizados estudos de interação dos complexos (1-5) com a HSA. Constataram-se valores altos das constantes de ligação complexos-HSA (da ordem 109 M-1) e alterações na estrutura secundária da proteína. Os parâmetros termodinâmicos de interação com o DNA e HSA indicaram que as interações clusters-biomoléculas também apresentam contribuições de caráter hidrofóbico / In this work a class of trinuclear ruthenium carboxylates coordinated to ortho-metallated ligands was presented. The electronic, electrochemical and photophysical properties of these complexes were investigated, as well as anticancer activity and interactions with target biomolecules, DNA and HSA. Synthesis and characterization of ligands (L2) C18H10N4, (L3) C19H12N4, (L4) C18H9ClN4, precursors (1) [Ru3O(OAc)6(CH3OH)3]CH3COO, (2) [Ru3O(OAc)6(CO)(CH3OH)2], (3) [Ru3O(OAc)6(CO)(py)2], (4) [Ru3O(OAc)6(py)2(CH3OH)]PF6 and the complexes (1-5), [Ru3O(OAc)5(py)2(L)] PF6, (where py = pyridine, L1 = dppn, L2 = dppz, L3 = dppzCH3, L4 = dppzCl, L5 = phen). NMR data showed that the ortho-metallation of phenazine ligands affects the structure of the complexes, with severe symmetry lowering. On the other hand, the investigation of the electronic and electrochemical properties indicated that presence of different substituents and the basicity of the ortho-metallated ligands influence little the properties of the unit [Ru3O]+. In terms of the electronic structure of the complexes, this effect indicates that there are no significant -type interactions between the orbitals of the [Ru3O]+ unit and ortometalated ligands. This fact may arise from the lack of planarity between the [Ru3O]+ unit and the phenazine ligands. The results of cytotoxicity in tumor cell and non-tumor cell lines showed that the complexes have a greater cytotoxic effect against tumor cells than free ligands, as well as low cytotoxicity against the non-tumor cell. These results have shown that the series with ortometal ligands brings the best performing examples already observed in our research group, compared to other trinuclear acetates of ruthenium with -oxo bridge, against melanoma cancer. The interaction studies with target biomolecules showed that the complexes interact with DNA and HSA. With the DNA, we observed interactions of an electrostatic nature, with contribution of the intercalation mechanism as the size and extent of conjugation of the orthomolected ligands increases, and the intercalation process is favored in the case of complex (1) with the dppn binder. Interaction studies of the complexes (1-5) with the HSA were performed. High complex-protein association constants (of the order 109 M-1) and alterations in the secondary structure were observed in the presence of the complexes (1-5). The thermodynamic parameters of interaction with DNA and HSA indicated that the clusters-biomolecules interactions also present hydrophobic contributions

Neste estudo, foram sintetizados complexos de ródio com aminoácidos e aminoácidos N-protegidos. Os compostos sintetizados foram caracterizados por análise elementar, espectrofotometria nas regiões do infravermelho e ultravioleta-visível, susceptibilidade magnética, ressonância magnética nuclear de próton e calorimetria exploratória diferencial. As técnicas analíticas utilizadas permitiram avaliar a estrutura dos complexos de ródio obtidos. Nos complexos sintetizados com aminoácidos, a ligação ocorreu pelos átomos de nitrogênio do grupamento amina e pelo oxigênio do grupo carboxila, formando anéis quelato de cinco membros, estrutura esta distinta da apresentada por compostos diméricos de ródio (II). Este modo de coordenação típico de carboxilatos de ródio dimérico, foi alcançado fazendo-se o bloqueio do grupamento amino, direcionando assim a coordenação do aminoácido, aos átomos de ródio, através dos dois oxigênios da carboxila. Numa etapa posterior, o grupo protetor foi removido por ataque ácido, tomando o complexo, anteriormente solúvel em solventes apoiares, totalmente solúvel em água, sendo mantida a estrutura de gaiola. Partindo-se dos complexos de ródio (II) sintetizados com aminoácidos N-bloqueados, foram obtidos adutos com o ácido isonicotínico, que se mostraram mais hidrossolúveis do que os complexos iniciais. Os compostos [Rh2(Boc-Gly)4)(I), [Rh2(Boc-L-Ala)4)(II) e seus respectivos adutos com o ácido isonicotínico foram submetidos a ensaios biológicos in vitro, onde foi avaliada a citotoxicidade destes sobre células tumorais K562, U937 e de tumor de Ehrlich. O aduto [Rh2(Boc-L-Ala)4](AIN)2(III) também foi submetido a um ensaio in vivo, de sobrevida. Camundongos portadores de tumor ascite de Ehrlich, tratados com solução do complexo (III), tiveram um aumento significativo de sobrevida, com formação de tumor sólido. Os complexos (I), (II), [Rh2(Boc-L-Val)4)(IV), [Rh2(Boc-L-Leu)4](V) e [Rh2(Boc-D-Phe)4)(VI) foram avaliados quanto ao seu potencial catalítico, em reações de hidrogenação. Os resultados foram expressos em termos de conversão de substrato em função do tempo de reação, número de rotação, freqüência de rotação e curvas TT x TTG. O complexo (I) apresentou atividade semelhante ao acetato de ródio (II), que foi utilizado como complexo de referência. Os demais compostos, (II), (V) e (VI) mostraram-se mais ativos que o acetato de ródio (II), nas reações de hidrogenação de hexeno-1 em etanol. / In this study, rhodium complexes were synthesized using amino acids and N-protected amino acids as ligands. The synthesized compounds were characterized by elemental analysis, IR and UVVis spectroscopy, magnetic susceptibility, proton magnetic nuclear resonance and diferential scanning calorimetry. The used analytical techniques allowed us to evaluate the structure of the obtained rhodium complexes. In the amino acids complexes, the binding occured through nitrogen atoms of the amino group and through the oxygen atom of the carboxyl group, forming chelate rings of five members, being these structures different from those presented by rhodium (II) carboxylates. This coordination mode was achieved protecting the amino group. In a next stage, the protecting group was removed by acid attack, turning the previously soluble in apolar solvents complex, totally soluble in water, being maintained the cage structure. From the N-protected amino acids rhodium (II) complexes synthesized, we obtained the isonicotinic acid adducts, more hydrossoluble than the original complexes. Antitumor activity of rhodium complexes [Rh2(Boc-Gly)4](I), [Rh2(Boc-L-Ala)4](II) and its isonicotinic acid adducts, was evaluated in vitro ( cell cultures K562, U937 and Ehrlich) and the compound [Rh2(Boc-L-Ala)4](AIN)2(III) was also submitted to a in vivo assay. Mices bearing Ehrlich ascite tumor, when treated with complex (III) solution, had a significant increase life span, with formation of solid tumor. The complexes (I), (II), [Rh2(Boc-L-Val)4](IV), [Rh2(Boc-L-Leu)4](V) and [Rh2(Boc-D-Phe)4](VI) were also tested in catalytic hydrogenation reactions. The results were expressed in terms of substrate conversion, turnover number, turnover frequency and TT x TTG curves. The complex (I) presented catalytic activity similar to the rhodium acetate (II), that was used as reference complex. The other compounds, (II), (V) and (I) exhibited improved catalytic behavior compared to rhodium (II) acetate in hydrogenation reactions using 1-hexene as substrate.

Radiossensibilizadores são definidos como agentes químicos que aumentam a sensibilidade das células hipóxicas à radiação, visando o aumento da eficácia da radioterapia no tratamento do câncer. Alguns Carboxilatos de Rh (II) e compostos nitroimidazólicos têm sido testados como radiossensibilizadores em doses elevadas de radiação, obtendo-se resultados significativos. Neste trabalho, foram sintetizados vários carboxilatos e um amidato de Rh (II): propionato, butirato, trifluoroacetato, citrato e trifluoroacetamidato, assim como os seus respectivos adutos com metronidazol, de fórmula geral: [Rh2(RCOO)4metro2] (R = CH3, C2H5, C3H7, C5 H7O5, e CF3) para o caso dos carboxilatos e [Rh2(CF3CONH) 4 metro2] para o aduto de trifluoroacetamidato. Os compostos foram caracterizados por análise elementar, espectroscopia eletrônica, infravermelho e de ressonância magnética nuclear de próton. O resultado desta caracterização permitiu estabelecer as rotas de síntese confirmando a formação dos carboxilatos tipo ponte e a presença do metronidazol nas posições axiais, numa relação 1:2. O efeito radiossensibilizador desses complexos de Rh (II) foi testado in vitro, irradiando-se, em atmosfera hipóxica, células de ovário de hamster chinês (CHO k1), na presença dos complexos, utilizando-se raios gama provenientes de uma fonte de 60Co, com doses de 2,7 e 4,3 Gy. Foi realizado teste de citotoxicidade para determinar as concentrações atóxicas de cada composto, eliminando a possibilidade de morte celular devido ao efeito tóxico dos mesmos. Na dose 2,7 Gy não houve nenhum efeito interessante; já com a dose de 4,3 Gy o [Rh2(CH3 COO)4] mostrou uma atividade radiossensibilizadora maior do que nos demais complexos. Os resultados foram semelhantes aos obtidos na literatura com doses de radiação até 10 vezes maiores. Devido à ausência de mudanças significativas no efeito radiossensibilizador entre os carboxilatos e amidato e seus respectivos adutos com metronidazol, foi determinada a constante de formação destes últimos, demonstrando que os mesmos sofrem decomposição quando em solução aquosa diluída. / Radiosensitizers are chemical agents that enhance the radiation sensitivity of hipoxic tumor cells aiming to better radiotherapy efficacy in the treatment of cancer. Some Rhodium (II) carboxylates and its adducts with nitroimidazole derivatives, have been tested as radiosensitizers in high doses of radiation, being obtained significant results. In this work, several Rhodium carboxylates and one Rhodium amidate previously described were synthesized: propionate, trifluoroacetate, citrate and , trifluoroacetamidate, as well as their respective adducts with nitroimidazole of general formula [Rh2(RCOO)4metro2] for the carboxylates and [Rh2(CF3CONH)4metro2] for the trifluoroacetamidate adduct. The compositions where characterized by elementary analysis, electronic and infrared spectroscopy and proton nuclear magnetic resonance. The results of that characterization allowed us to establish the synthesis routes and confirm the bridge type structure of the Rodhium compounds, beyond the presence of the metronidazole at the axial positions in the proportions of 1:2. The radiosensitizing effects of these Rh (II) complexes were tested in vitro by irradiation of Chinese hamster (CHO k1) cells under hipoxic atmosphere in the presence of the complexes, using gamma rays from a 60Co source and doses of 2,7 and 4,3 Gy. A cytotoxicity test has been performed to determinate the non-toxic concentrations of these compounds, in order to rule out the possibility of cellular death induced by the complexe´s cytotoxicity. A 2,7 Gy dose showed no interesting effects but under a 4,3 Gy dose, the complex Rh2(CH3 COO)4 showed a higher radiosensitizing effect than the order compounds and close to previously reported effects which required high radiation doses. As there was not a significant change in the radiosensitizing effect between the carboxylate and the amidate and their respective metronidazole adducts it was performed the measurement of the formation constant of that adducts. The results of that measurements gave evidence of adduct decomposition when in dilute aqueous solution.

Radiossensibilizadores são definidos como agentes químicos que aumentam a sensibilidade das células hipóxicas à radiação, visando o aumento da eficácia da radioterapia no tratamento do câncer. Alguns Carboxilatos de Rh (II) e compostos nitroimidazólicos têm sido testados como radiossensibilizadores em doses elevadas de radiação, obtendo-se resultados significativos. Neste trabalho, foram sintetizados vários carboxilatos e um amidato de Rh (II): propionato, butirato, trifluoroacetato, citrato e trifluoroacetamidato, assim como os seus respectivos adutos com metronidazol, de fórmula geral: [Rh2(RCOO)4metro2] (R = CH3, C2H5, C3H7, C5 H7O5, e CF3) para o caso dos carboxilatos e [Rh2(CF3CONH) 4 metro2] para o aduto de trifluoroacetamidato. Os compostos foram caracterizados por análise elementar, espectroscopia eletrônica, infravermelho e de ressonância magnética nuclear de próton. O resultado desta caracterização permitiu estabelecer as rotas de síntese confirmando a formação dos carboxilatos tipo ponte e a presença do metronidazol nas posições axiais, numa relação 1:2. O efeito radiossensibilizador desses complexos de Rh (II) foi testado in vitro, irradiando-se, em atmosfera hipóxica, células de ovário de hamster chinês (CHO k1), na presença dos complexos, utilizando-se raios gama provenientes de uma fonte de 60Co, com doses de 2,7 e 4,3 Gy. Foi realizado teste de citotoxicidade para determinar as concentrações atóxicas de cada composto, eliminando a possibilidade de morte celular devido ao efeito tóxico dos mesmos. Na dose 2,7 Gy não houve nenhum efeito interessante; já com a dose de 4,3 Gy o [Rh2(CH3 COO)4] mostrou uma atividade radiossensibilizadora maior do que nos demais complexos. Os resultados foram semelhantes aos obtidos na literatura com doses de radiação até 10 vezes maiores. Devido à ausência de mudanças significativas no efeito radiossensibilizador entre os carboxilatos e amidato e seus respectivos adutos com metronidazol, foi determinada a constante de formação destes últimos, demonstrando que os mesmos sofrem decomposição quando em solução aquosa diluída. / Radiosensitizers are chemical agents that enhance the radiation sensitivity of hipoxic tumor cells aiming to better radiotherapy efficacy in the treatment of cancer. Some Rhodium (II) carboxylates and its adducts with nitroimidazole derivatives, have been tested as radiosensitizers in high doses of radiation, being obtained significant results. In this work, several Rhodium carboxylates and one Rhodium amidate previously described were synthesized: propionate, trifluoroacetate, citrate and , trifluoroacetamidate, as well as their respective adducts with nitroimidazole of general formula [Rh2(RCOO)4metro2] for the carboxylates and [Rh2(CF3CONH)4metro2] for the trifluoroacetamidate adduct. The compositions where characterized by elementary analysis, electronic and infrared spectroscopy and proton nuclear magnetic resonance. The results of that characterization allowed us to establish the synthesis routes and confirm the bridge type structure of the Rodhium compounds, beyond the presence of the metronidazole at the axial positions in the proportions of 1:2. The radiosensitizing effects of these Rh (II) complexes were tested in vitro by irradiation of Chinese hamster (CHO k1) cells under hipoxic atmosphere in the presence of the complexes, using gamma rays from a 60Co source and doses of 2,7 and 4,3 Gy. A cytotoxicity test has been performed to determinate the non-toxic concentrations of these compounds, in order to rule out the possibility of cellular death induced by the complexe´s cytotoxicity. A 2,7 Gy dose showed no interesting effects but under a 4,3 Gy dose, the complex Rh2(CH3 COO)4 showed a higher radiosensitizing effect than the order compounds and close to previously reported effects which required high radiation doses. As there was not a significant change in the radiosensitizing effect between the carboxylate and the amidate and their respective metronidazole adducts it was performed the measurement of the formation constant of that adducts. The results of that measurements gave evidence of adduct decomposition when in dilute aqueous solution.