Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2017-09-06T12:46:35Z No. of bitstreams: 1 DissMAN.pdf: 2589036 bytes, checksum: 82bbd3895f9a5e39df35028736c8e29d (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-09-20T21:33:25Z (GMT) No. of bitstreams: 1 DissMAN.pdf: 2589036 bytes, checksum: 82bbd3895f9a5e39df35028736c8e29d (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-09-20T21:33:36Z (GMT) No. of bitstreams: 1 DissMAN.pdf: 2589036 bytes, checksum: 82bbd3895f9a5e39df35028736c8e29d (MD5) / Made available in DSpace on 2017-09-20T21:40:50Z (GMT). No. of bitstreams: 1 DissMAN.pdf: 2589036 bytes, checksum: 82bbd3895f9a5e39df35028736c8e29d (MD5) Previous issue date: 2017-05-12 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Cancers have become an increasingly relevant problem of public health in the last decades. Within neoplastic diseases, breast cancer is one of the most incidental in female population and related to a high mortality rate. Within types of breast cancer, triple-negative is the most aggressive one and prone to form metastasis to lung and brain. Because they do not express hormone receptors, triple-negative tumors do not have an auxiliary target therapy, thus, treatment is hampered and chemotherapy is the only option of treatment remaining for metastatic cases of this tumor type. However, chemotherapy drugs currently used, in some cases are not selective to tumor cells, acting only on the proportion of cells exposed to treatment or cells that are at certain stages of the cell cycle. Thus, non-tumor cells are affected and some neoplastic cells remain intact, characterizing tumor recurrences and resistance to treatment. Rosenberg and colleagues, in 1964, were responsible for the discovery of cisplatin, a metal and antiproliferative compound still widely used in therapies against various types of tumors, but despite its effectiveness, it has several side effects. Therefore, the search for more selective antitumor drugs for neoplastic cells and with fewer adverse effects is critical to advances in the treatment of cancer. With the limitations of cisplatin, new researches have been developed with ruthenium complexes. Ruthenium has properties that may justify its antitumor potential and selectivity for tumor cells; within them, the ability to imitate iron binding to many biomolecules, including transferrin and albumin. Previous studies have suggested the antitumor effects of ruthenium both in vitro and in vivo. Therefore, the aim of this study was to evaluate the chemosensitizing ability of the ruthenium complex [Ru(GA)(dppe)2]PF6, which we called Ru(GA), as well as its antitumor activity on triple-negative breast cancer cells (TNBC). In addition, differences between the in vitro behavior of cells treated with the compound and untreated cells were verified, as well as differences between the activity on tumor and non-tumor cells used in this study. The results demonstrated that the complex Ru(GA) was more efficient in inhibiting the proliferation of triple negative breast cancer cells MDA-MB-231, compared with the non-tumor cell line MCF-10A, which was more resistant to the complex. Furthermore, the compound was able to reduce the number and size of colonies, to modify the cytoskeleton and act inhibiting the migration ability of tumor cells. The complex also induced apoptosis by increasing the expression of pro-apoptotic genes such as Bax, Caspase-9, Caspase-3 and decreasing anti-apoptotic genes Bcl-2 in TNBC cells. Moreover, Ru(GA) was able to increase the expression of apoptotic proteins and sub-G1 phase distribution on tumor cells. Interaction assays with Ru(GA) and transferrin showed that this protein has a strong participation in the contact between ruthenium complexes and tumor cells, increasing their effectiveness. These results show that the complex Ru(GA) has antitumor potential against breast tumor cells and it might be a good alternative drug for the treatment of cancer. / Os cânceres têm se tornado um problema de saúde pública mundial cada vez mais relevante nas últimas décadas. Dentre os cânceres, o câncer de mama está entre os mais incidentes na população feminina, além de possuir um alto índice de mortalidade. Entre os tipos de câncer de mama, o triplo-negativo é o mais agressivo e propenso à metástases pulmonares e cerebrais. Por não possuir receptores hormonais, tumores triplo-negativos não possuem uma terapia alvo auxiliar e o tratamento é dificultado, sendo a quimioterapia a única opção de tratamento para os casos metastáticos deste tipo tumoral. No entanto, os medicamentos quimioterápicos utilizados atualmente, além de não serem seletivos para as células tumorais, atuam apenas sobre a proporção de células expostas ao tratamento ou que estejam em determinadas fases do ciclo celular. Assim, células não tumorais são atingidas e algumas células neoplásicas ainda permanecem intactas, caracterizando as recorrências tumorais e resistência ao tratamento. Rosenberg e colaboradores em 1964 foram responsáveis pela descoberta da cisplatina, um composto metálico e antiproliferativo ainda muito utilizado em terapias contra vários tipos de tumores, porém, apesar de sua eficácia, apresenta diversos efeitos colaterais. Portanto, a busca por medicamentos antitumorais mais seletivos para as células neoplásicas e com menos efeitos adversos torna-se fundamental para os avanços no tratamento do câncer. Com as limitações da cisplatina, novas pesquisas vêm sendo desenvolvidas com complexos de rutênio. O rutênio possui propriedades que podem justificar seu potencial antitumoral e seletividade para células tumorais, dentre elas, a capacidade de mimetizar o ferro na ligação a muitas biomoléculas, incluindo a transferrina e albumina. Estudos anteriores sugeriram os efeitos antitumorais do rutênio tanto in vitro quanto in vivo. Este trabalho teve como objetivo avaliar a capacidade quimiosensibilizadora do complexo de rutênio [Ru(GA)(dppe)2]PF6, o qual foi chamado de Ru(GA), bem como sua atividade antitumoral sobre células tumorais de mama do tipo triplo-negativo (TN). Adicionalmente, eventuais diferenças no comportamento in vitro de células tratadas com o composto em relação às células não tratadas foram verificadas, bem como diferenças entre a atividade nas células tumorais e não-tumorais utilizadas. Os resultados demonstraram que o complexo Ru(GA) foi o mais eficaz em inibir a proliferação das células tumorais de mama triplo negativas, da linhagem MDA-MB-231, em comparação com a linhagem não tumoral de mama MCF-10A que se mostrou mais resistente ao complexo. Ainda, o composto foi capaz diminuir o número e tamanho de colônias, de modificar o citoesqueleto e de atuar inibindo a capacidade migratória das células tumorais. O complexo também foi capaz de induzir apoptose aumentando a expressão de genes pró-apoptóticos como Bax, Caspase-9, e Caspase-3 e diminuindo a expressão genes anti-apoptóticos Bcl-2, nas células tumorais de mama triplo negativas. Além destes efeitos, o Ru(GA) aumentou a expressão de proteínas apoptóticas e a taxa de células em sub-G1 nas células tumorais. Ensaios de interação do Ru(GA) com transferrina mostraram que esta possui forte participação no contato entre complexos de rutênio e células tumorais, aumentando assim sua eficácia. Esses resultados mostram que o complexo Ru(GA) possui potencial antitumoral para células tumorais de mama, podendo ser uma nova alternativa de fármaco para o tratamento do câncer.

Partant des composés ATiO3 (A=Ba, Pb, Sr) bien connus pour leurs propriétés de type ferroélectriques, il est possible de concevoir des super-réseaux de basse dimensionnalité (multi-couches, phases de type ,…) où ces propriétés peuvent être modulées en fonction de la composition, de l'épaisseur des couches mises en jeu, des contraintes aux interfaces. Nous proposons ici d'étudier par calculs de premiers principes les instabilités structurales et la dynamique de réseau pour des systèmes simples dans cette famille. En définissant clairement les zones interfaciales et de cœur des couches, et en étudiant la convergence de leurs propriétés en fonction de l'épaisseur, ce travail vise à établir des potentiels interatomiques modèles, analytiques et transférables, pour la prédiction des propriétés dynamiques et des instabilités structurales de super-réseaux étendus et/ou complexes. / The aim of the present thesis is to investigate, from first-principles, the ferroelectricproperties and related phase transition behaviors in perovskite type compounds. Wewill not focus only on the bulk perovskite systems, but also on related layered superlatticeswhere the interface may play an important role and induce new phenomena.

Made available in DSpace on 2014-10-09T12:41:57Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:04:43Z (GMT). No. of bitstreams: 0 / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:41:57Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:04:43Z (GMT). No. of bitstreams: 0 / O 68Ga é um radionuclídeo promissor para a medicina nuclear, decaindo por emissão de pósitrons com abundância de 89%, apresentando tempo de meia vida física de 68 minutos, o que é compatível com a farmacocinética de muitas biomoléculas e substratos de baixo peso molecular. Outra característica importante é a sua disponibilidade por um sistema de gerador, onde o radionuclídeo pai, 68Ge (t1/2 = 270,95 dias) é adsorvido em uma coluna e o filho, 68Ga, é eluído na forma iônica 68Ga3+. O desenvolvimento dos geradores de 68Ge/68Ga teve início na década dos anos 60, mas o seu uso clínico começou a ser aceitável e relevante apenas recentemente. O método de separação do 68Ge do 68Ga mais utilizado é o sistema cromatográfico de troca iônica, devido sua praticidade de operação, mas outros sistemas de geradores já foram propostos, como de extração por solvente e técnica de evaporação. Atualmente, os geradores de 68Ge/68Ga são disponíveis comercialmente tanto com colunas utilizando matrizes inorgânicas preparadas com TiO2 ou SnO2 como também usando resina orgânica. A eficiência de eluição do 68Ga varia de 70 % a 80 %, apresentando uma queda ao longo do tempo. Os níveis de contaminação do 68Ge vão de 10-2 a 10-3 %, porém ocorre um aumento nos níveis de contaminação após longos períodos de uso. Mesmo com todos os avanços tecnológicos, ocorridos nas últimas décadas, no desenvolvimento dos geradores de 68Ge/68Ga, o eluato de 68Ga dos geradores comerciais ainda não é adequado para uso direto em seres humanos e algumas melhorias nos sistemas precisam ser feitas para diminuir os níveis de contaminação de 68Ge e impurezas químicas. O objetivo principal deste trabalho foi desenvolver um sistema de gerador de 68Ge/68Ga com o qual se pudesse eluir o 68Ga com qualidade necessária para uso clínico. O comportamento químico do Ge e do Ga foi avaliado em vários materiais adsorvedores inorgânicos. Foram desenvolvidos dois tipos de sistemas de geradores de 68Ge/68Ga utilizando o TiO2 como material adsorvedor: sistema de eluição com pressão manual e sistema de eluição a vácuo, controlado. As eficiências dos geradores foram similares às encontradas nos geradores comerciais, assim como os níveis de impurezas no eluato. Um novo método para o controle radionuclídico foi desenvolvido e apresentou resultados satisfatórios para determinação da contaminação do 68Ge no eluato do gerador. Foi proposto um protótipo de gerador capaz de fornecer 68Ga com a qualidade necessária para ser utilizado em aplicações médicas. / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

The work presented in this thesis has broadly established a few findings about the structure¬hyperpolarizability relation in molecular compounds: First, by measuring βHRS of an organic keto-enol tautomer, benzoylacetanilide in a binary solvent, I have shown that the first hyperpolarizability can be manipulated favourably by changing the composition of the solvent or by altering the pH of the solution. BA which exists in the pure keto form in water and as a keto-enol tautomer in ethanol, co-exists in equilibrium with the keto and enol forms at pH 11 in aqueous solution. The β value of the anion form is 709 x 10¬30 esu , whereas that of the enol is 232 x 10-30 esu and of the keto is 88 x 10-30 esu. There is an enhancement of β by ~ 8 times for the anion and ~3 times for the enol compared to the keto form. This opens up the possibility of finding large nonlinearities in organic molecules by simply ionizing it. Second, in organometallic complexes of divalent Ru, the first hyperpolarizability could be manipulated by altering the valence state of the metal center by oxidation or reduction or by introducing highly polarisable halogen atoms as substitutions in ligands attached to the metal center. The enhancement of first hyperpolarizability was observed in mononuclear [RuII(acac)2(CH3CN)2] complex by 1.7 times when the metal center was oxidized from RuII to RuIII. As it is already known that the complexes like [(acac)2Ru-bptz-Ru(acac)2] produce stable mixed valent compound, the enhancement of β by ~1.6 times is appearing because of that species only. Exploring Large Nonlinearity in Tautomers In this thesis I have taken a linear ketone for studying the effect of structure on β via the enol and anion formation mediated by solvent and pH of the medium. In the present study the proton transfer in BA took place in the ground state of the ketone and the enol or anion are produced in the ground states. The proton transfer reaction (tautomerism) can also happen in the excited state as well in some molecules where there is a substantial barrier to the proton transfer reaction in the ground state. In such systems, once the ketone is excited using ultraviolet light the barrier to proton transfer in the medium is overcome and a proton transfer in the excited state takes place and the enol is produced. Since such a system will be at higher energy, it will be interesting to do a two-laser experiment where the excited state hyperpolarizability is measured in a time resolved manner and the β value is determined in the excited state. Building Molecular Nonlinearity in Step-by-Step Electron Transfer In this thesis, I have dealt with a binuclear complex of Ru(II) which in one-step electrochemical oxidation produced a mixed valence compound which had substantially higher β value compared to the unoxidized complex. In this way it is possible to build a multicentered complex and see if sequential one-electron transfer and subsequent oxidation/reduction of the metal centers produce a mixed-valent metal compound with large molecular nonlinearity. The indication from the present study is that such a scheme should double the β value in each one-electron transfer step. Also the linker group/moiety between the successive metal centers will play an important role in dictating the efficiency of electron transfer. If the metal d-electrons in a multinuclear complex are linked through a π-conjugation, one would expect manifold enhancement of β. Such metal arrays can also be designed in 2 or 3 dimensions. The dimensionality of the multinuclear metal complexes can easily be changed by supramolecular design and synthesis strategy. Such metal networks may or may not generate large β molecules since electronic polarization in such systems may not be superimposable in a coherent fashion and may not add in a positive sense. All these remain to be tested and explored in the future.

Atomically flat colloidal semiconductor CdSe nanoplatelets (NPLs) with precisely controlled thickness possess a range of unique optoelectronic properties. Here, we study the growth of CdSe, CdTe, and CdS NPLs with the aim of synthesizing thicker NPLs in order to extend their optical activity further into the lower energy/larger wavelength range. We employ cadmium halides, which lead to faster reaction kinetics as confirmed by control experiments with cadmium hydroxide as a Cd-precursor. Addition of halides in all cases led to the formation of thicker NPL species, as compared with the corresponding syntheses without these additives. Analysis of a recent theoretical model of the platelet growth mechanism confirms an earlier suggestion that reducing both the reaction enthalpy and the surface energy of CdSe, by replacing acetate ligands with chloride ions, should indeed lead to thicker NPLs as observed. We noticed a formation of Cd0-metal nanoparticles in the first stage of the synthesis by preparing the Cd-precursor, which is another key finding of our work. We assume that these particles can serve as an active cadmium source facilitating the growth of the NPLs. The resulting 6 ML CdSe NPLs exhibited bright photoluminescence with quantum yield of up to 50%, exceptionally narrow spectrum centered at 582 nm with full width at half-maximum of approx. 11 nm, and small Stokes shift of 2 nm. Moreover, we demonstrated the synthesis of heterostructured core/shell CdSe/CdS NPLs based on 6 ML CdSe platelets, which also exhibited bright fluorescence. This work shows the possibility to overcome energetic barrier limiting the size (thickness) control by using appropriate promoters of the growth of CdSe, CdTe, and CdS 2D structures.

M. Tech. (Department of Chemistry, Faculty of Applied and Computer Sciences), Vaal University of Technology. / Water scarcity due to limited resources and pollution of the little available water by organic and inorganic contaminants remains as one of the critical issues of the 21st century. Several treatment methods have been developed, with some being used successfully at industrial scale but many challenges including secondary sludge generation, high operation costs, high maintenance costs and high energy input were observed. In this study, the adsorption process was explored as an effective means for the removal of Cr(VI) ions from aqueous solution due to its economic feasibility and use of abundantly available adsorbents. Amongst the many available adsorbents, this work focused on exploring functionalized activated carbons (ACs) as adsorbents for Cr(VI) ions due to their favorable adsorption characteristics which involve large surface area, high porosity, and high radiant stability. The iron oxide functionalized polyethyleneimine activated carbon-silica composites were prepared through co-precipitation of Fe(II) and Fe(III) over Macadamia activated carbon to form the AC-Fe3O4 co-shell which was reacted with tetraethylorthosilicate (TEOS) and the polyethyleneimine (PEI). The different adsorbents prepared were labelled AC-Fe3O4, AC-Fe3O4-SiO2 and AC-Fe3O4-SiO2-PEI. The adsorbents were further characterized using elemental analysis (CHNS), thermo gravimetric analysis (TGA), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET), transmission electron spectroscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). FTIR displayed successful attachment of Fe3O4 and SiO2 with bands at 404 and 786 cm-1 being assigned to the asymmetric vibration of Fe-O and Si-O-Si while the asymmetric stretch of Si-OH is observed at 1066 cm-1. XRD showed the presence of magnetite particles in the adsorbents confirmed by the JCPDS 00-019-0629. EDS revealed the presence of Fe, Si, and N atoms which can relate to successful incorporation of the desired functional groups. Each of these materials were evaluated for their Cr(VI) ion removal through batch adsorption experiments where one parameter at a time was varied while all others were fixed. The parameters investigated included the effect of pH, contact time, initials Cr(VI) concentration, adsorbent dosage concentration and temperature. The optimum conditions were obtained at pH 3, initial concentration 2.5 mg/L, contact time of 120 min for AC-Fe3O4-SiO2-PEI. The optimization of each parameter was done in order to determine the conditions in which the adsorbents work best in the uptake of Cr(VI). All the three studied adsorbents showed acceptable adsorption performance for the removal of Cr(VI) from aqueous solutions. Adsorption isotherms studied confirmed that the adsorption data in all the three adsorbents fitted well into the Langmuir isotherm, demonstrating a homogeneous monolayer coverage. Regarding the kinetic studies, the adsorption data were best described by the pseudo-second order rate model with R2 values of 0.974, 0.974 and 0.962 for AC-Fe3O4, AC-Fe3O4-SiO2 and AC-Fe3O4-SiO2-PEI, respectively. The adsorption capacity observed from the present study (6.62, 3.92 and 5.48 for AC-Fe3O4, AC-Fe3O4-SiO2 and AC-Fe3O4-SiO2-PEI, respectively) were satisfactory and suitable as compared to those reported in literature. Thermodynamics data of the adsorption processes revealed a feasible spontaneous endothermic adsorption process which also confirmed that the reaction process occurred through chemisorption.

The thesis consists of eight chapters of which the first chapter presents a brief overview of inorganic nanostructures. Synthesis and magnetic properties of MnO and NiO nanocrystals are described in Chapter 2, with emphasis on the low-temperature ferromagnetic interactions in these antiferromagnetic oxides. Chapter 3 deals with the synthesis and characterizations of nanocrystals of ReO3, RuO2 and IrO2 which are oxides with metallic properties. Pressure-induced phase transitions of ReO3 nanocrystals and the use of the nanocrystals for carrying out surface-enhanced Raman spectroscopy of the molecules form Chapter 4. Use of ionic liquids to synthesize different nanostructures of semiconducting metal sulfides and selenides is described in Chapter 5. Synthesis of Mn-doped GaN nanocrystals and their magnetic properties are described in Chapter 6. A detailed investigation has been carried out on the growth kinetics of nanostructures of a few inorganic materials by using small-angle X-ray scattering and other techniques (Chapter 7). The study includes the growth kinetics of nanocrystals of Au, CdS and CdSe as well as of nanorods of ZnO. Results of a synchrotron X-ray study of the formation of nanocrystalline gold films at the organic-aqueous interface are also included in this chapter. Chapter 8 discuses the use of the organic-aqueous interface to generate Janus nanocrystalline films of inorganic materials where one side of the film is hydrophobic and other side is hydrophilic. This chapter also includes the formation of nanostructured peptide fibrils at the organic-aqueous interface and their use as templates to prepare inorganic nanotubes.

From the Proceedings of the 1972 Meetings of the Arizona Section - American Water Resources Assn. and the Hydrology Section - Arizona Academy of Science - May 5-6, 1972, Prescott, Arizona / Storm runoff from the Tucson metropolitan area is unsuitable for most uses without processing. A lysimeter comprised of a grass and soil filter was constructed and is being evaluated as a water-quality treatment facility. The lysimeter is 200 feet long, 4 feet wide and 5 feet deep, and contains homogeneous calcareous loam covered by common grasses. Experimental apparatus was installed to divert less than a cubic foot per second of runoff from urbanized Arcadia Watershed. Runoff flows by gravity over the lysimeter, where surface inflow, surface outflow and subsurface outflow are measured and sampled. Four trials, each associated with a discrete runoff event, were conducted in the fall of 1971. Water samples were analyzed for inorganic chemical constituents, chemical oxygen demand (COD), coliforms, turbidity and sediment contents. Subsurface-outflow samples from initial trials were high in COD and total dissolved solids, representing soil flushing or leaching. Concentrations of inorganics reached a maximum value within a few hours of initial seepage, and then decreased. The peaking represents a salt build-up between trials. Concentrations of COD, coliforms, turbidity and sediment in subsurface-outflow samples decreased significantly during each trial. Surface-outflow samples had lower turbidity, COD, bacteria and sediment contents than surface-inflow samples. Turbidity, suspended and volatile solids, coliforms and COD in runoff samples may be reduced by grass and soil filtration. Increased grass development and soil settling work to produce a better quality effluent. Quantification of the lysimeter's effectiveness will be useful for urban watershed management.

From the Proceedings of the 1974 Meetings of the Arizona Section - American Water Resources Assn. and the Hydrology Section - Arizona Academy of Science - April 19-20, 1974, Flagstaff, Arizona / This study attempts to determine the water quality changes in stock tanks and what factors are instrumental in the changes, and to assess the effects of the changes. Algal growth was the most prominent change taking place in the tanks with time. Little change in the water chemistry was noted until just before the tanks dried up. As algae died, ions tied up by the algae were released to the water, causing an increase in concentration of many of the nutrients. In order to determine the impact of various factors on algal growth, the data from eight stock tanks were analyzed by stepwise linear regression. Although 20 variables were used in the complete analysis, six variables were associated with 56.3 percent of the variance: time (since first sampling), total n, potassium, pH, inflow (recharge to the tanks), and hco3 concentration. Time and total n explained 51.3 percent of the variance, and potassium increased the variance to 52.8 percent. The pH reversed the relative positions of time and total n, with total n becoming dominant. The last two factors, inflow and hco3 were negative (resulting in a decrease in algal population) and increased the coefficient of variance to 56.3 percent.