Darbe tirta Co6Om (m=0-9) nanodalelių ir PPI dendrimerų optinės savybės, siekiant nustatyti ar PPI dendrimerai galėtų būti naudojami dirbtinių neuroninių tinklų, skirtų aptikti Co nanodaleles, kūrimui. Tyrimo rezultatai yra: 1) Co6Om (m=0-9) nanodalelių absorbcijos spektrų tyrimai parodė, kad absorbcijos intensyvumas 500-700 nm intervale mažėja, kai deguonies atomų skaičius didinamas iki 5. Absorbcijos intensyvumas vėl pradeda didėti, kai deguonies atomų skaičius tampa 6. 2) Teoriškai ir eksperimentiškai ištirta glikodendrimero su triptofano molekulėmis spektro prigimtis 200 - 400 nm intervale. Nustatyta, kad minėtame bangų ilgių diapazone stebimas triptofano molekulės π→π* sužadinimas. 3) Tirti PPI dendrimerai galėtų būti naudojami kaip neuroniniai tinklai, skirti aptikti Co nanodaleles. / In this research our aim was to investigate possibilities to use PPI dendrimers as a neural network for detecting Co nanoparticles. Our investigation results are: 1) Intensity of absorption of the Co6Om (m=0-9) particles should decrease in the 500-700 nm region with increasing of oxygen number till 5, and should increase again when number of oxygen atom is 6; 2) Nature of spectrum of PPI dendrimers with Tryptophan molecule in 200-400 nm range was investigated both theoretically and experimentally. It is obtained, that in above mentioned wavelength region absorption is due to π→π* excitation of tryptophan units; 3) Investigated PPI dendrimers could be used as an artificial neural network for detecting Co nanoparticles.

Darbe tirtos funkcionalizuotų dendrimerų optinės savybės sintetinant sidabro nanodaleles panaudojus glikodendrimerą kaip terpę. Keičiant išorinius faktorius, tokius kaip temperatūra (20 oC ir 45 oC), medžiagų koncentracija (1:5, 1:10 ir 1:20) ar skirtingo bangos ilgio šviesa (532nm ir 632,8nm), užauginome sidabro nanodaleles. Gauti rezultatai rodo, jog sidabro nanodalelių dydžiui didžiausią įtaką daro tik [dendrimeras/AgNO3] santykis. Kuo jis didesnis – tuo sidabro dalelės yra didesnės. Tuo tarpu tiek temperatūra, tiek šviesa didesnės reikšmės dalelių susiformavimui neturi. Remiantis gautais rezultatais galime tvirtinti, kad tirti PPI-G4 glikodendrimerai gali būti naudojami kaip matrica sidabro nanodalelių formavimui. / We prepared silver nanoparticles using a fourth-generation PPI glycodendrimer were about from 5nm to 10nm in size, and that the higher the [dendrimer/AgNO3] ratio, the larger were the metal particles. The results suggest that the temperature and different wavelength of light does not affect the nanoparticle size by using PPI-G4 glycodendrimer as a template. The characteristic absorption peak at around 400nm corresponds to a plasmon band. The splasmon spectrum of nanoparticles is affected by the nature of the metal and the status of aggregation of the particles. The single peak indicates that the silver particles are of spherical shape.

Organic photovoltaics (OPVs) that have been studied to date have poor power conversion efficiencies. This dissertation focuses on various molecular designs that could lead to both a fundamental understanding of photoinduced charge separation at a molecular level and also provide a solution to improve bulk properties of organic materials to overcome the poor efficiencies of OPV devices. The effect of molecular architectures on the efficiency of electron transfer, a primary step in OPVs functioning, is evaluated in this work. We have shown that even though dendrimer provides an interesting architecture for efficient electron transfer due to the presence of multiple peripheries around a single core, this architecture leads to trapping of charge at the dendritic core. This results in a decrease in the electron transfer efficiency in solution and also limits the possibility of charge transport to the electron in a photovoltaic device. Non-conjugated polymers containing conductive EDOT units at side chains were also designed and synthesized. The frontier energy levels of these polymers can be easily tuned by changing the conjugation lengths of side chain EDOT oligomers. Moreover, by incorporating crosslinkable units as co-side chains, the absorption bandwidth of these polymers can be manipulated as well.

Thesis (PhDApSc)--University of South Australia, 2002.

Doenças cardiovasculares podem ocasionar manifestações clínicas graves como infarto agudo do miocárdio e acidentes vasculares trombóticos, constituindo a principal causa de morte no mundo, fato esse que desperta grande interesse da indústria farmacêutica. As causas normalmente estão relacionadas à elevação dos níveis de colesterol e à agregação plaquetária, que acarretam eventos vaso-oclusivos. Entre as alternativas terapêuticas para o controle e prevenção das doenças cardiovasculares podem-se destacar os inibidores da 3-hidroxi-3-metilglutaril coenzima-A redutase (HMG-CoA redutase), popularmente conhecidos como estatinas. A rosuvastatina merece destaque nessa classe de fármacos, devido à maior seletividade e potência na redução dos níveis de colesterol LDL. O ácido acetilsalicílico, antiinflamatório não-esteróide, também representa uma importante alternativa terapêutica para prevenção de doenças cardiovasculares, devido à sua ampla aceitação como inibidor da agregação plaquetária. Considerando seus mecanismos de ação, estatinas e ácido acetilsalicílico podem ser usados em conjunto para a prevenção de doenças cardiovasculares. Face ao exposto e tendo-se em vista a importância dos dendrímeros como transportadores de fármacos na latenciação, o presente trabalho teve como objetivo desenvolver o pró-fármaco dendrimérico potencialmente ativo em doenças cardiovasculares contendo rosuvastatina e ácido acetisalicílico. Diversas metodologias de síntese foram realizadas na tentativa de obtenção do pró-fármaco dendrimérico composto por mio-inositol ou etilenoglicol como foco central, ácido L(-)-málico e etilenoglicol como espaçantes e rosuvastatina e ácido acetilsalicílico como compostos bioativos. Parte dos intermediários propostos foi sintetizada e purificada com sucesso. As maiores dificuldades encontradas foram a purificação dos compostos e a hidrólise seletiva da proteção do ácido málico protegido. Adicionalmente, realizaram-se estudos computacionais para prever a liberação dos fármacos do pró-fármaco dendrimérico. / Cardiovascular diseases can lead to several clinical manifestations such as myocardial infarction and stroke. Those diseases represent the main cause of death globally and this fact triggers a great interest from the pharmaceutical industries. The causes are usually related to high cholesterol levels and platelet aggregation, which are responsible for the vaso-occlusive events. Among the available drug therapy for control and prevention of cardiovascular diseases, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), popularly known as statins, can be highlighted. Rosuvastatin deserves mention in this class of drugs due to its greater selectivity and potency in reducing the levels of LDL cholesterol. Aspirin, a nonsteroidal anti-inflammatory, also represents an important drug therapy for treatment and prevention of cardiovascular diseases, due to its widespread acceptance as a platelet aggregation inhibitor. Considering their mechanism of action, aspirin and statin can be used in association for prevention of cardiovascular diseases. This said and taken into account that dendrimers are important as carriers in prodrug design the purpose of this work was the synthesis of dendrimer prodrugs potentially active in cardiovascular diseases containing aspirin and rosuvastatin. Several synthetic methods have been used with the aim to synthesizing the dendrimer produgs composed of myo-inositol or ethyleneglycol as core, L-(-)-malic acid and ethyleneglycol as spacer groups and rosuvastatin and aspirin as bioactive compounds. Some of the proposed intermediates was synthesized and purified successfully. The main difficulties were purification of compounds and selectivy desprotection of protected malic acid. Additionally, computational studies were performed in order to predict the release of those drugs from dendrimer prodrugs

O câncer de mama constitui o segundo tipo de câncer mais frequente no mundo e o mais comum entre as mulheres, devido ao seu alto grau de malignidade. A quimioterapia é utilizada no tratamento de câncer de mama com presença de metástase, dentre os fármacos mais utilizados está o paclitaxel, que atua na desestabilização dos microtúbulos na divisão celular, levando a célula neoplásica a apoptose, porém, o paclitaxel é uma molécula extremamente lipofílica, solubilizada em Cremophor® EL, um tensoativo altamente tóxico utilizado na formulação comercial. O objetivo deste trabalho foi desenvolver complexos dendriméricos com paclitaxel para a otimização da terapia do câncer de mama. Para a quantificação do paclitaxel nos sistemas de liberação desenvolvidos foram validados métodos analíticos por espectrofotometria UV-Vis e por cromatografia líquida de alta eficiência. Os métodos foram seletivos, linear, precisos e exatos. Para a obtenção de uma formulação concentrada os complexos foram liofilizados. O complexo PAMAM-G4-NH2-Paclitaxel foi obtido em diversos meios reacionais, com diferentes faixas de pH, sendo o tampão Hepes, pH 7,4, e água; os meios que obtiveram melhores resultados de complexação, posteriormente foram analisados por DLS e NTA, com diâmetro médio de partícula em 160 nm e potencial zeta catiônico. A caracterização do complexo obtido foi realizada por análises de espectrofotometria no infravermelho e ressonância magnética nuclear. O estudo in vitro de liberação do paclitaxel a partir dos complexos dendriméricos foi realizado utilizando membrana de acetato de celulose e quantificação por CLAE. O perfil de liberação demonstrou que após 156 horas, no máximo 35% do fármaco foi liberado. A liberação lenta representa uma vantagem para o tratamento de tumores sólidos, pois idealmente o sistema de liberação deve manter o fármaco encapsulado durante a circulação sanguínea e liberá-lo uma vez acumulado passivamente no sítio tumoral. A citotoxicidade foi avaliada na linhagem tumoral 4T1, através do ensaio do MTT. O complexo PAMAM-G4-NH2-Paclitaxel apresentou citotoxicidade 5 vezes maior que a formulação comercial. Na avaliação antitumoral in vivo do complexo, foram avaliados a curva do crescimento tumoral, o registro de peso, a sobrevivência dos animais e a proliferação celular com o anticorpo ki 67. O complexo dendrimérico teve efeito estatisticamente significativo na redução do volume tumoral e, através da análise de imunohistoquimica foi confirmada a redução da proliferação celular. Portanto, o complexo PAMAM-G4-NH2-Paclitaxel pode representar uma estratégia promissora para o tratamento de câncer de mama e posteriormente deverá ser avaliada por meio de estudos clínicos. / Breast cancer is the second most common type of cancer worldwide and the most common among women, due to its high degree of malignancy. Chemotherapy is used to treat breast cancer metastasis, among the most widely used drugs are paclitaxel, which operates in the microtubules destabilization in cell division, resulting in neoplastic cell apoptosis, however, paclitaxel is a highly lipophilic molecule which is solubilized in Cremophor® EL, a highly toxic surfactant used in the commercial formulation. The aim of this study was to develop dendrimeric complex with paclitaxel for the optimization of breast cancer therapy. To quantify the paclitaxel in the developed delivery systems, the analytical method was validated by UV-Vis spectrophotometry and high-performance liquid chromatography. The methods were selective, linear, accurate and precise. To obtain a concentrated formulation, the complexes were lyophilized. The PAMAM-G4-NH2-paclitaxel complex was obtained in various reaction media with different pH ranges, with the HEPES buffer, pH 7.4, and water. The media with obtained the best complexation were subsequently analyzed by DLS and NTA, and the mean particle diameter was 160 nm with a cationic zeta potential. The characterization of the obtained complex was performed by infrared and nuclear magnetic resonance spectrophotometric analysis. The in vitro release study of paclitaxel from the dendrimeric complex was evaluated using membranes of cellulose acetate and quantified by HPLC. The release profile showed that after 156 hours at most 35% of the drug was released. The extended release is an advantage for the solid tumors treatment, because ideally the release system should keep the drug encapsulated during blood circulation and release it over time passively accumulated in the tumor site. Cytotoxicity was assessed in tumor cell line 4T1, using the MTT assay, the PAMAM-G4-NH2 paclitaxel complex showed cytotoxicity 5 times greater than the commercial formulation. In in vivo antitumor evaluation of the complex were evaluated curve of tumor growth, the weight record, the animal survival and cell proliferation with the antibody ki 67. Dendrimer complex had statistically significant effect in reducing tumor volume and through the immunohistochemical analysis the results were confirmed the reduction of cell proliferation. Therefore, the PAMAM-G4- NH2-paclitaxel complex can represent a promising strategy for the breast cancer treatment and should be further evaluated by means of clinical studies

M.Sc. (Chemistry) / With the increase in the number of new Human Immunodeficiency Virus (HIV) infection and mortality rate worldwide partly due to diagnostic drawbacks which gives false negatives during the window period, it is imperative to find an alternative method of detection. The need for prompt, bed-side and field applicable analytical devices for biomedical purposes cannot be over emphasized in our fast paced world today. As a contribution to meeting these challenges, this dissertation reports (i) the development of novel electrochemical DNA/RNA aptamer biosensor for HIV sensing and (ii) the development of other DNA sequence specific electrochemical biosensors. These biosensors were based on composite platforms of dendrimer and gold nanoparticles...

Le neutrino est l'une des douze particules élémentaires du modèle standard. Il se caractérise par une charge électrique nulle et une masse extrêmement petite. De nombreuses expériences ont été conçues afin d'étudier les propriétés des neutrinos. Malgré les avancées effectuées jusqu'à présent, la nature du neutrino est, encore aujourd'hui, inconnue. La collaboration NEMO (Neutrino Ettore Majorana Observatory) étudie la double désintégration bêta sans émission de neutrino, phénomène radioactif très rare, afin de découvrir la nature du neutrino et de déterminer s'il est, ou non, identique à son antiparticule. Aujourd'hui, la collaboration NEMO construit un nouveau détecteur baptisé SuperNEMO. Le gaz présent dans le détecteur requiert une concentration en radon inférieur à 100 µBq/m3, afin de minimiser le bruit de fond radioactif. La purification du gaz est réalisée grâce l'adsorption du radon par des matériaux microporeux. Dans ce travail, nous avons développé au CPPM (Centre de Physique des Particules de Marseille) un banc de mesures pour quantifier l'adsorption du radon par divers matériaux, afin d'en tirer un modèle, et atteindre les conditions de pureté requise pour SuperNEMO. En parallèle avec l'étude d'adsorbants disponibles, et de manière à mieux explorer la problématique de l'adsorption du radon, nous avons synthétisé et étudié au CINaM (Centre Interdisciplinaire de Nanoscience de Marseille) des composés polyaromatiques hydrocarbonés étoilés et des polymères aromatiques branchés ou dendritiques, incorporant du soufre, pour adsorber le radon. / The neutrino is one of the twelve elementary particles from the standard model. It is characterize by a neutral electrical charge and an extremely low mass. Many experiments have been set up in order to study the properties of neutrino. Despite scientific breakthrough, the nature of this particle is still unknown up to now. The NEMO collaboration is studying the neutrinoless double beta decay, a very rare radioactive process, to find out the nature of neutrino and to know if the neutrino is equivalent to the antineutrino. Today, the NEMO collaboration is building a new detector called SuperNEMO. The gas inside the detector need to have a concentration in radon below 100 µBq/m3, to minimize the radioactive background. The purification of this gas is achieved from the adsorption of radon by microporous material. In this work, we have developed in CPPM a bench test to measure the radon adsorption by various materials, in order to propose an adsorption model, and to reach the purity condition needed for SuperNEMO. Along with the study on adsorbents available and to better understand the radon adsorption, we synthetized and studied at CINaM star-shape polyaromatic hydrocarbons and branched or dendritic aromatic polymers, incorporating sulfur, to adsorb radon.

Les nano-objets ou nanoparticules sont des systèmes de taille nanométrique. Dans le domaine de l’oncologie, ils sont capables de transporter des agents anticancéreux et/ou des macromolécules comme des gènes ou des protéines, de sorte qu’ils s’accumulent préférentiellement dans le tissu tumoral. Ainsi, les nanoparticules ont pour but de diminuer la quantité de principe actif libre dans l’organisme, responsable de toxicités. Elles permettent en clinique d’améliorer la balance bénéfice/risque des agents de chimiothérapies conventionnels. Ce sont de véritables plateformes qui permettent de s’affranchir de certains excipients toxiques contenus dans la formulation du paclitaxel (Cremophor El). Ainsi, au cours de ce travail nous nous sommes intéressés dans un premier temps aux nanoparticules d’or (Au-NP) produites par ablation laser femtoseconde. Nous avons ainsi caractérisé ces Au-NP sur le plan physico-chimique et biologique, et mis en évidence leur internalisation et leur innocuité. Dans un deuxième temps, nous avons évalué l’efficacité pharmacologique de conjugués dendron-paclitaxel sur des cultures cellulaires 2D et 3D et mis en avant la libération prolongée intracellulaire du paclitaxel et son effet retard. Compte-tenu des propriétés observées, ces nanoparticules sont de bons candidats pour un futur développement. En effet, la liaison de ces deux nanostructures entre elles permettra l’obtention d’un nano-objet aux propriétés de théranostiques. / Nano-objects or nanoparticles can be readily fabricated with their size being controlled typically in the range of 1–100 nm. In the field of oncology, they can be used for drug delivery, as their composition/structure may be engineered to load anticancer drugs, macromolecules or proteins. Indeed, the delivery of anticancer drugs through a nanoparticle-based platform offers many attractive features. Nanoparticle-based drugs are synthetized to significantly improve the benefit/risk ratio of conventional chemotherapeutics. They allow overcoming some toxic excipients in the formulation of paclitaxel (Cremophor El). In this work, we first studied the physico-chemical and biological properties of Au-NPs synthetized by femtosecond laser ablation and we investigated their safety and cellular uptake. Second, we evaluated the anticancer activity of dendron-paclitaxel conjugates in 2D and 3D cell cultures and showed a delayed effect of this new formulation. Based on these results, the studied nanoparticles are good candidates for future development. By combining the two nano-objects, we will obtain nanoparticles with theranostic properties.

La synthèse et la caractérisation de la structure électronique de nanosystèmes contenant des complexes redox en forme d'étoile ou dendritiques ont été conduites en vue d'applications dans le domaine des matériaux et de la catalyse. La première partie est consacrée à la description de ces nanomatériaux, la seconde partie à la synthèse et aux propriétés de nanoparticules métalliques pour des applications biomédicales et catalytiques, et la troisième partie à la mise en œuvre et optimisation des propriétés catalytique de nanoréacteurs moléculaires et nanoparticulaires. Ces nanoréacteurs catalytiques se sont montrés particulièrement efficaces pour des réactions de métathèse oléfiniques et pour des réactions de couplage carbone-carbone de type Miyaura-Suzuki. Les réactions catalytiques ont pu être conduites dans l'eau avec des quantités extrêmement faibles de catalyseur. Dans ce dernier cas, le caractère « homéopathique » des catalyseurs a même pu être démontré. / Synthesis and characterization of the electronic structures of star-shape and dendritic and nanoparticle-centered nanosystems containing redox-active groups have been carried out for applications in materials chemistry and catalysis. The first part of the manuscript describes molecular nanomaterials, the second part nanoparticles for catalytic and biomedical applications, and the third part catalytic processes optimized in nanoreactors of molecular or nanoparticle types. The catalytic nanoreactors have been shown to be extremely efficient for olefin metathesis reactions and for Miyaura-Suzuki reactions. Catalytic reactions could be performed in water using extremely low amounts of nanoreactor-stabilized catalysts. In the latter example, catalysis is even « homeopathic ».