This dissertation presents subwavelength optics with focus on the theory and applications of subwavelength apertures in a metal film. Two main issues regarding the optics with subwavelength apertures are investigated. As the first issue, the extraordinary optical transmission (EOT) through a single hole in a metallic waveguide is presented. A total transmission through a single subwavelength aperture is theoretically predicted for a perfect electric conductor regardless of the aperture size, without relying on aperture arrays and surface corrugations as presented in previous works. The waveguide EOT is then applied to boost the optical throughput of an apertured near-field scanning optical microscope (NSOM) probe. Using a new structure for the apertured NSOM probe which allows for waveguide EOT, the optical throughput and the damage threshold are boosted by 100× and 40× as compared to a conventional structure, and the experimental findings are backed-up by comprehensive finite-difference time-domain (FDTD) simulations. Single fluorescent molecules are scanned using the EOT apertured NSOM probe, and a spatial resolution of 62 nm is achieved. As the second issue, subwavelength apertures are found useful for optical trapping. A small dielectric particle can significantly change the optical transmission through an aperture by dielectric loading, and subsequently, a large optical force is induced which favors trapping. A self-induced back-action (SIBA) optical trap is designed using a circular nanohole in a gold film. Trapping of 50 nm polystyrene particle is experimentally achieved, which is not possible using a conventional single beam optical tweezers. The circular nanohole SIBA trap works beyond the perturbative regime, as proven by FDTD simulations and a Maxwell stress tensor analysis. We further improve the nanohole trapping using a double-nanohole, which is more sensitive for small dielectric changes due to the intense local field enhancement between its two sharp tips. A single 12 nm silica sphere is experimentally trapped using the double-nanohole, as the smallest trapped dielectric particle reported. We also achieve the trapping of a single protein – a bovine serum albumin (BSA) protein with a hydrodynamic radius of 3.4 nm in the folded form. The trapped BSA is also unfolded by the large optical force, as confirmed by experiments with changing optical power and changing pH. The high signal-to-noise ratio of 33 in monitoring single protein trapping and unfolding shows a tremendous potential for using the double-nanohole as a sensor for protein binding events at a single molecule level. / Graduate

Many biological processes, pathogens, and pharmaceuticals act upon, cellular membranes. Accordingly, cell membrane mimics are attractive targets for biosensing, with research, pathology, and pharmacology applications. Lipid bilayers represent a versatile sensor functionalization platform providing antifouling properties, and many receptor integration options, uniquely including transmembrane proteins. Bilayer-coated sensors enable the kinetic characterization of membrane/analyte interactions. Addressed theoretically and experimentally is the self-assembly of model membranes on plasmonic sensors. Two categories of plasmonic sensors are studied in two parts. Part I aims to deposit raft-forming bilayers on planar nanoaperture arrays suitable for multiplexing and device integration. By vesicle fusion, planar bilayers are self-assembled on thiol-acid modified flame-annealed gold without the need for specific lipid head-group requirements. Identification of coexisting lipid phases is accomplished by AFM imaging and force spectroscopy mapping. These methods are successfully extended to metallic, plasmon-active nanohole arrays, nanoslit arrays and annular aperture arrays, with coexisting phases observed among the holes. Vis-NIR transmission spectra of the arrays are measured before and after deposition, indicating bilayer detection. Finally, the extraction of membrane proteins from cell cultures and incorporation into model supported bilayers is demonstrated. These natural membrane proteins potentially act as lipid-bound surface receptors. Part II aims to encapsulate in model lipid bilayers, metallic nanoparticles, which are used as probes in surface enhanced Raman spectroscopy. Three strategies of encapsulating particles, and incorporating Raman-active dyes are demonstrated, each using a different dye: malachite green, rhodamine-PE, and Tryptophan. Dye incorporation is verified by SERS and the bilayer is visualized and measured by TEM, with support from DLS and UV-Vis spectroscopy. In both parts, lipid-coated sensors are successfully fabricated and characterized. These results represent important and novel solutions to the functionalization of plasmonic surfaces with biologically relevant cell membrane mimics.

Biodegradable, edible wheat gluten films offer a renewable alternative to plastic food packaging or can be incorporated directly in the food product. Wheat gluten is a good option because it forms a fibrous network, lending strength and elasticity to films. The goal of this research project was to produce, with a water-based film formulation and methodology, smooth, homogeneous wheat gluten films with low water vapour permeability (WVP). The water-based film formulation also served to compare the FT Wonder wheat cultivar, grown in Ontario, to commercially produced wheat gluten and determine the effect of wheat source on the film properties, surface morphology, surface hydrophobicity, WVP, and film swelling in water for different pH, temperature and casting surface conditions. Fluorescence, SPR, and casting formulation viscosity provided preliminary information on the mechanism of film formation and on gluten protein structure induced by modifying the film formulation. This research provides an alternate use for some Ontario wheat cultivars based on their properties in films compared to commercial sources of gluten. As a result, using Ontario cultivars to prepare gluten film packaging material has potential as an alternate source of income for Ontario farmers. This research also defines the film properties for gluten films produced from aqueous solutions, helping to identify processing parameters that could bring gluten films on par with plastic packaging and make gluten films a viable alternative food packaging material. Finally, it was determined that the water vapour permeability of wheat gluten films was not correlated to film surface contact angle.

Protein aggregation is commonly encountered during the manufacture of protein-based bioproducts in processing such as protein expression, purification, refolding, shipping and storage (Volkin and Middaugh, 1992; Brange, 2000). Aggregation may shorten the shelf-life of pharmaceutical proteins (Frokjaer and Otzen, 2005) and induce severe hypersensitivity (Rosenberg, 2006). In addition, several diseases ranging from Alzheimer’s disease to cystic fibrosis are associated with protein aggregation in the form of amyloid fibrils and plaques (Dobson, 1999; Luheshi et al., 2008). Hence, studies on protein aggregation, especially those dealing with high concentrations of proteins, are highly demanded in both academic and industrial laboratories. To address the aforementioned issues, physicochemical factors affecting protein aggregation were investigated systematically in this project. Strategies were developed to inhibit protein aggregation during renaturation and to enhance protein stability against aggregation during and after production, especially when dealing with high protein concentrations. ∆5-3-Ketosteroid isomerase (KSI) was used as a model for aggregation studies during protein renaturation due to its intrinsic aggregation properties. KSI was overexpressed as inclusion bodies (IBs) in Escherichia coli (E. coli). Cost- and time-efficient combination of chemical extraction and one-step affinity purification ensured the production of denatured KSI with high purity at high yield. Several key factors, including protein concentration and ionic strength, were determined to greatly influence KSI aggregation during renaturation. Polymer addition (PEG 3000 and Eudragit S-100) was found to alter KSI aggregation behaviour in a polymer-specific manner, as quantified using reversed phase-high performance liquid chromatography (RP-HPLC) analysis. Light scattering for second virial coefficient (SVC) measurement, surface plasmon resonance (SPR), and microfluidics were applied to study the fundamental mechanism of protein aggregation. Lysozyme was further introduced as a control protein for comparison with KSI. A rapid lumped method was established to measure specific refractive index (∂n/∂c) and SVC values for KSI and lysozyme, which provided quantitative and qualitative information on thermodynamic interactions of molecules in solution. SPR and microfluidics were also used to explore protein aggregation properties. To our best knowledge, it is the first time SPR and microfluidics have been used to investigate protein aggregation behaviour. Both SPR and microfluidics present significant potential for assessing protein aggregation and diagnosis or drug screening of protein aggregation related diseases. The chemical and physical stability of proteins needs to be maintained after successful refolding to ensure an acceptably long shelf life, especially at high protein concentration (Chang and Hermsdorf, 2002). The pharmaceutical effects of lectins on cell growth provided incentive for studies to improve their stability. Human galectin-2 (hGal-2, a homodimeric lectin) was used as a study model in this project. Mutations were introduced at one of the two Cys residues (C57A, C57M, and C57S). Only the C57M variant was highly expressed in bacteria in soluble form. No aggregate of this mutant was detected during 3 weeks of storage. hGal-2 C57M also facilitated site-directed introduction of poly(ethylene glycol) (PEG) into the remaining sulfhydryl group (Cys75). Product analysis revealed rather complete conjugation with one PEG chain per protein subunit in homodimer. Neither secondary structure alteration nor the absence of binding ability to a glycoprotein (asialofetuin) was observed. The results document the feasibility of tailoring a human galectin for enhanced stability against aggregation as well as monoPEGylation, which enables further testing of biological properties including functionality as a growth regulator and the serum clearance rate of hGal-2.

Orientador: Sidney Jose Lima Ribeiro / Banca: Younes Messaddeq / Banca: Denis Boudreau / Banca: Cid Bartolomeu de Araujo / Banca: Anna Marie Ritcey / Banca: Mauricio da Silva Baptista / Banca: Rogéria Rocha Gonçalves / Resumo: Na área biomédica, existe uma crescente demanda por nanossistemas multifuncionais para realização de imageamento e terapia simultaneamente, visando um diagnóstico precoce e máximo benefício terapêutico. Nanopartículas para conversão ascendente de energia (UCNPs) vêm sendo propostas como a sonda biológica ideal devido às suas vantagens únicas relacionadas ao fenômeno de upconversion apresentado por materiais contendo íons lantanídeos, isto é, emissão no visível obtida sob excitação no infravermelho, tais como penetração profunda nos tecidos, uma baixa taxa de autofluorescência e um fotodano mínimo. Além disso, as propriedades luminescentes dos íons lantanídeos podem ser usadas para termometria por serem fortemente dependentes da temperatura. A termometria luminescente é uma técnica de não-contato e alta resolução que vem ganhando atenção na nanomedicina uma vez que a temperatura é um parâmetro fundamental para o funcionamento das células. Danos térmicos às células podem ser localmente fotoinduzidos pelo uso de nanoestruturas metálicas iluminadas em sua banda de ressonância plasmônica por causa da sua elevada absortividade. A primeira parte deste trabalho consiste no desenvolvimento de um sistema multifuncional baseado em nanocascas de ouro (AuNSs) decoradas com UCNPs podendo ser utilizadas para aumentar e medir a temperatura em escala nanométrica. Este sistema foi desenvolvido com a finalidade de uma eventual utilização como agente em terapia fototérmica (PTT), na qual a capac... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In the biomedical field, there is an increasing demand for multifunctional nanosystems to perform imaging and therapy simultaneously, aiming at early diagnosis and maximum therapeutic benefit. Upconversion nanoparticles (UCNPs) have been proposed as an ideal bio-probe because of their unique advantages related to the upconversion phenomenon presented by materials containing lanthanide ions, e.g. visible emission obtained under near-infrared (NIR) excitation, such as deep tissue penetration, low autofluorescence background and low photo-damage. Moreover, the luminescent properties of lanthanide ions may be used for thermometry because of a strongly temperature-dependent effect. Luminescence nanothermometry is a noncontact and high-resolution technique that has been gaining attention in nanomedicine since temperature is a fundamental parameter in events that occur in cells. The thermal damage of cells may be locally photoinduced by using metal nanostructures illuminated at their localized surface plasmon resonance (LSPR) band because of the enhancement of light absorption. In this work, a multifunctional system was designed combining gold nanoshells (AuNSs) and UCNPs intended as an optical heater and temperature probe at the nanoscale. This system was studied aiming its application as an agent for photothermal therapy (PTT), guided by the thermometer capacity of UCNPs, which allows to optimize the therapeutic benefits. The synthesis of NaGdF4 UCNPs doped with ions Yb3+:Er3+ was... (Complete abstract click electronic access below) / Résumé: Dans le domaine biomédical, il y a une demande croissante pour les nanosystèmes multifonctionnels pour effectuer simultanément l'imagerie et la thérapie, en visant le diagnostic précoce et apporter du bénéfice thérapeutique maximal. Les nanoparticules à conversion ascendante d'energie (UCNPs) ont été proposés comme une bio-sonde idéale en raison de leurs avantages uniques liés au phénomène d'upconversion présenté par les matériaux contenant des ions lanthanides, c'est-à-dire l'émission visible obtenue sous excitation dans le proche infrarouge (NIR), tels qu'une meilleure pénétration dans les tissus, une bas taux d'autofluorescence et un photo-dommage minimal. De plus, les propriétés luminescentes des ions lanthanides peuvent être utilisées pour la thermométrie en raison de leur forte dépendance sur la température. La thermométrie par luminescence est une technique sans contact et à haute résolution qui a attiré l'attention en nanomédecine puisque la température est un paramètre clé dans le fonctionnement des cellules. Des dommages thermiques aux cellules peuvent être localement photoinduits par l'utilisation de nanostructures métalliques illuminées dans leur bande de résonance plasmon en raison de leur absorptivité élevée. La prémière partie de ce travail implique le développement d'un système multifonctionnel, basé sur des nanocoquilles d'or (AuNSs) décorées avec des UCNPs, pouvant être utilisé pour augmenter et mesurer la température à l'échelle nanométrique. Ce système a é... (Résumé complet accès életronique ci-dessous) / Doutor

Made available in DSpace on 2016-06-02T20:15:16Z (GMT). No. of bitstreams: 1 TeseVEEC.pdf: 1596360 bytes, checksum: a1bc2433298a824834d595326d99a608 (MD5) Previous issue date: 2005-03-22 / Financiadora de Estudos e Projetos / In the present work, the localization properties of the single-particle and collective excitations subjected to a random potential in the AlGaAsSi alloys and in the intentionally disordered GaAs/AlGaAs:Si superlattices (SL s)were investigated by magnetoresistance and Raman scattering. As it is well known, the fluctuations of the eletronic potential, which occur in doped SL s and alloys destroy the translational invariance giving rise to a spatial coherence length of the elementary excitations and, as consequence, cause the breakdown of the Raman selection rules leading to the broadening and assymetry of the Raman lines. The analysis of the shape of the spectral lines allows one to determine the coherence lengths of the elementary excitations involved in the Raman process and thus, to study their localization properties. It was shown that the Landau damping determines the localization lengths of the collective plasmon-like excitations in bulk AlGaAs alloy. Meanwhile the localization lengths of both,the single-particle and collective excitations are limited by disorder in the intentionally disordered superlattices. The localization lengths of the plasmon-like excitations obtained by Raman Spectroscopy was compared with the phase-breaking lengths measured by Magnetoresistance. We had verified that in superlattices the localization length of the individual electron was found to be considerably larger than localization length corresponding to the collective excitations. This suggests that the effect of disorder has weaker influence on the electrons than on their collective motion and that the interaction, which gives rise to the collective effects, increase the localization. / Neste trabalho, as propriedades de localização das excitações de uma partícula e das excitações sujeitas a um potencial aleatório em ligas AlGaAs:Si e em superredes intencionalmente desordenadas GaAs/AlGaAs:Si (SL s) foram investigadas por magnetoresistência e espalhamento Raman. Como é bem sabido, as flutuações do potencial eletrônico, que ocorrem em SL s e ligas dopadas destroem a invariância translacional permitindo o aparecimento de um comprimento de localização espacial das excitações elementares e, como consequência, causando a relaxação das regras de seleção o que provoca a largura e assimetria das linhas Raman. A análise da forma das linhas espectrais permite determinar os comprimentos de localização das excitações elementares envolvidas no processo Raman e assim, estudar suas propriedades de localização. No caso das ligas AlGaAs:Si, mostrou-se que o amortecimento de Landau determina os comprimentos de localização das excitações coletivas tipo plasmon. Entretanto, nas SL s intencionalmente desordenadas, as propriedades de localização tanto das excitações de uma partícula quanto das excitações coletivas são limitadas pela desordem. Os comprimentos de localização das excitações tipo plasmon obtidos por espectroscopia Raman foram comparados com os comprimentos de coerência de fase do elétron medidos por magnetoresistência. Verificamos que em superredes o comprimento de localização das excitações de uma partícula é consideravelmente maior que o comprimento de localização das excitações coletivas. Isto sugere que o efeito da desordem é mais fraco para os elétrons do que para os movimentos coletivos e que a interação permite que os efeitos coletivos aumentem a localização.

L'intérêt de la recherche fondamentale pour les morceaux nanométriques de métaux nobles est principalement dû à la résonance localisée des plasmons de surface (LSPR) dans l'absorption optique. Différents aspects, liés à la compréhension théorique de la LSPR dans le cas de clusters de métaux nobles de taille dite intermédiaire, sont étudiés dans ce manuscrit. Afin d'avoir une vision plus large nous utilisons deux approches : l'approche électromagnétique classique et le formalisme ab initio en temps réel de la théorie de la fonctionnelle de la densité dépendant du temps (RT-TDDFT). Une comparaison systématique et détaillée de ces deux approches souligne et quantifie les limitations de l'approche électromagnétique lorsqu'elle est appliquée à des systèmes de taille quantique. Les différences entre les excitations plasmoniques collectives et celles impliquant les électrons d, ainsi que leurs interactions, sont étudiées grâce au comportement spatial des densités correspondantes. Ces densités sont obtenues en appliquant une transformée de Fourier dans l'espace à la densité obtenue par les simulations DFT utilisant une perturbation delta-kick. Dans ce manuscrit, des clusters de métaux nobles nus et protégés par des ligands sont étudiés. En particulier, motivé par de récents travaux sur les phénomènes d'émergence de plasmon, l'étude par TD-DFT de nano-alliages Au-Cu de taille tout juste inférieure à 2nm à fourni de subtiles connaissances sur les effets d'alliages sur la réponse optique de tels systèmes. / The fundamental research interest in nanometric pieces of noble metals is mainly due to the localized surface-plasmon resonance (LSPR) in the optical absorption. Different aspects related to the theoretical understanding of LSPRs in `intermediate-size' noble-metal clusters are studied in this thesis. To gain a broader perspective both the real-time \ai formalism of \td density-functional theory (RT-TDDFT) and the classical electromagnetics approach are employed. A systematic and detailed comparison of these two approaches highlights and quantifies the limitations of the electromagnetics approach when applied to quantum-sized systems. The differences between collective plasmonic excitations and the excitations involving $d$-electrons, as well as the interplay between them are explored in the spatial behaviour of the corresponding induced densities by performing the spatially resolved Fourier transform of the time-dependent induced density obtained from a RT-TDDFT simulation using a $\delta$-kick perturbation. In this thesis, both bare and ligand-protected noble-metal clusters were studied. In particular, motivated by recent experiments on plasmon emergence phenomena, the TDDFT study of Au-Cu nanoalloys in the size range just below 2~nm produced subtle insights into the general effects of alloying on the optical response of these systems.

Les récepteurs de chimiokines sont des régulateurs essentiels de la migration cellulaire dans le cadre de la surveillance immunitaire, et le développement. Les récepteurs CCR5 et CXCR4 sont de plus spécifiquement impliqués dans les métastases cancéreuses et l'infection par le VIH. Nous avons développé un système permettant de sur-exprimer ces deux RCPGs. Afin de s'affranchir des problèmes de toxicité inhérents à l'expression des protéines membranaires en bactérie notre approche de production consiste à adresser les protéines vers les corps d'inclusion d'E. coli grâce à une fusion protéique N-terminale permettant de hauts niveaux d'expression. Après purification en conditions dénaturantes, les protéines sont alors repliées en présence de surfactants originaux, les amphipoles. La validation de cette nouvelle approche pour les récepteurs des chimiokines représente un des objectifs principaux de ce travail. Afin de tester la fonctionnalité des protéines repliées, une série d'outils a été développée : des versions modifiées des chimiokines ont été produites (RANTES pour CCR5 et SDF 1a pour CXCR4). La fonctionnalité des chimiokines a été évaluée au niveau moléculaire et cellulaire. L'interaction entre le récepteur replié en amphipole et son ligand a été testé par résonance de plasmons de surface (SPR). Différents types de surfaces fonctionalisées avec le récepteur de chimiokine replié en amphipole ont été explorés au cours de ce travail. A la fin de ce projet, la production des chimiokines et de leur récepteur a été mise au point. L'accès à ces outils ouvre la voie à de futures études moléculaires telles que la compréhension de la dimérisation du récepteur ou la détermination de la stoechiométrie du complexe. / Chemokine receptors are critical regulators of cell migration in the context of immune surveillance, inflammation and development. The GPCRs (G protein-coupled receptors) CCR5 and CXCR4 are specifically implicated in cancer metastasis and HIV-1 infection. An expression system to over-express these two GPCRs was developed. To overcome the toxicity problem of membrane protein expression in bacterial system, the production approach consists in targeting the proteins towards E. coli inclusion bodies thanks to a N-terminal fusion allowing a high yield expression. After purification under denaturing conditions, these GPCRs were then folded using original polymeric surfactants: the amphipols. The validation of this new approach for the chemokine receptor production is one of the goals of this work. In order to assess the functionality of the folded proteins, series of tools have been developed: engineered chemokine ligands (RANTES for CCR5 and SDF1a for CXCR4) were produced. The functionality of chemokines was evaluated at cellular and molecular levels. Interaction between the receptor folded in amphipols and its ligand was evaluated using Surface Plasmon Resonance (SPR) technique. Several types of surfaces, functionalized with the chemokine receptor/amphipol complex have been explored in this work. At the end of this project the productions of chemokines and their receptors has been set up. These established tools open the way to future studies, at the molecular level, in order to, for instance, investigate receptor dimerization and complex stoichiometry.

L'immunité, un système de défense incroyable, protège la plupart des organismes vivants des pathogènes nuisibles. Les composantes innée et acquise de l'immunité travaillent ensemble pour assurer une protection efficace de l'homme ainsi que de tous les autres vertébrés à mâchoires. Les cellules dendritiques, la composante de l'immunité innée, passent régulièrement en revue les tissus périphériques, capturent et traitent les agents pathogènes envahisseurs et enfin, présentent les antigènes aux lymphocytes T pour stimuler les réponses immunitaires adaptatives spécifiques. Ces cellules reconnaissent les organismes étrangers à l'aide de plusieurs "Pattern Recognition Receptors" (PRRs), qui se lient spécifiquement à des molécules à la surface des agents pathogènes, dits "Pathogen Associated Molecular Patterns (PAMPs). Parmi les PRR, les récepteurs lectine de type C (CLRs) ont un rôle important dans la reconnaissance et dans la capture des pathogènes. Cependant, DC-SIGN, l'un de ces CLR, peut être détourné par de nombreux agents pathogènes dangereux, y compris le VIH, afin de promouvoir leur infection. Ce travail vise à développer des antagonistes de DC-SIGN, qui serait en mesure de bloquer l'utilisation de ce récepteur par des agents pathogènes. Pour atteindre cet objectif, la stratégie du développement de ligands glycomimétique de DC-SIGN et la présentation multivalente des glycomimétiques monovalents sélectionnés a été employée. Les études présentées ont été réalisées en collaboration avec plusieurs groupes de chimistes, qui ont conçu et synthétisé différents composés glycomimétiques ainsi que différentes plates-formes multivalentes. Des ligands monovalents de DC-SIGN basés sue le mannose, le fucose et sur les composés C-glycosidiques ont été explorés et différentes plates-formes de valence avec différents modes de présentation dans l'espace ont été étudiées. En utilisant la résonance plasmonique de surface (SPR), l'activité des composés à inhiber DC-SIGN a été estimée. De plus, les composés ont été évalués pour leur sélectivité pour DC-SIGN par rapport à la Langerine, un autre CLR ayant un rôle protecteur contre l'infection par le VIH. Certains de ces composés ont été caractérisés par cristallographie aux rayons X et par spectrométrie RMN. Les études de SPR de composés multivalents ont confirmé l'amélioration de l'activité, mais a également révélé des complications possibles. Dans l'ensemble, ces études ont permis d'identifier les deux meilleurs nouveaux composés et de suggérer des perspectives pour l'amélioration de ces composés et des plates-formes de présentation multivalentes. / An amazing defense system, the immunity, protects most of the living organisms from harmful pathogens. The innate and acquired immunity components work together to provide efficient protection of humans as well as all other jawed vertebrates. Dendritic cells, the component of the innate immunity, routinely survey the peripheral tissues, capture and process the invading pathogens, and finally, present the antigens to the T cells to boost the pathogen specific adaptive immune responses. These cells recognize the foreign organisms with the help of multiple pattern recognition receptors (PRRs), which specifically bind molecules on the pathogen surfaces, so-called pathogen associated molecular patterns (PAMPs). Among PRRs, the C-type lectin receptors (CLRs) have an important role in pathogen recognition and capturing. However, one of these CLRs, DC-SIGN, has been shown to be hijacked by many dangerous pathogens, including HIV, to promote their infection. This work aims to develop the antagonists of the C-type lectin receptor DC-SIGN, which would be able to block the use of this receptor by pathogens. To achieve that, the strategy of the development of glycomimetic ligands of DC-SIGN and the multivalent presentation of the selected monovalent glycomimics has been employed. The presented studies were accomplished in collaboration with several chemists groups, who have designed and synthesized different glycomimetic compounds as well as different multivalent platforms. The mannose-based, fucose-based and the C-glycosidic compounds were explored as monovalent DC-SIGN ligands, and multivalent platforms with different valence as well as ligand presentation in space were investigated. Using surface plasmon resonance (SPR), the activity of the compounds to inhibit DC-SIGN was estimated. Moreover, the compounds were evaluated for their selectivity to DC-SIGN vs langerin, another CLR with a protective role from HIV infection. Some of the compounds were structurally characterized by X-ray crystallography and NMR spectrometry studies. The SPR studies of multivalent compounds confirmed the improved activity, but also revealed possible complications Overall, these studies allowed to identify two new monovalent leads and to draw perspectives for their further improvement, and suggested the improvement of multivalent presentation platforms.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-05-31T20:37:34Z No. of bitstreams: 1 EdiRozemberghBrasileiroDaSilvaBrandao_TESE.pdf: 21206961 bytes, checksum: 7b22e84f9eeadd1446a3596114b8ad22 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-01T19:35:34Z (GMT) No. of bitstreams: 1 EdiRozemberghBrasileiroDaSilvaBrandao_TESE.pdf: 21206961 bytes, checksum: 7b22e84f9eeadd1446a3596114b8ad22 (MD5) / Made available in DSpace on 2017-06-01T19:35:34Z (GMT). No. of bitstreams: 1 EdiRozemberghBrasileiroDaSilvaBrandao_TESE.pdf: 21206961 bytes, checksum: 7b22e84f9eeadd1446a3596114b8ad22 (MD5) Previous issue date: 2016-10-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Neste trabalho, apresentamos um estudo te?rico da propaga??o das ondas eletromagn?ticas em estruturas de multicamadas denominadas de Cristais Fot?nicos. Dentro deste escopo, este trabalho possui tr?s vertentes. Na primeira parte, estudamos teoricamente os espectros de transmiss?o em quasi-cristais fot?nicos unidimensionais, composta de materiais SiO2 (A) e TiO2 (B), organizada seguindo a sequ?ncia de Octonacci, onde o en?simo est?gio da multicamada Sn ? dado pela regra Sn=Sn-1Sn-2Sn-1, para n ? 3 e com S1=A e S2=B. A express?o de transmit?ncia foi obtido empregando um c?lculo te?rico baseado no m?todo da matriz de transfer?ncia. Para ondas incidentes normalmente, observamos que, para uma mesma gera??o, os espectros de transmiss?o para ondas transversais el?ctricas (TE) e ondas transversais magn?ticas (TM) s?o iguais ao menos de forma qualitativa, e eles apresentam uma propriedade de escala em que um comportamento auto-similar ? obtido, como uma evid?ncia de que esses espectros s?o fractais. Os espectros mostram regi?es onde os band gaps unidirecionais emergem para as gera??es espec?ficas da estrutura fot?nica de Octonacci, exceto para ondas TM. Para ondas TE, notamos que todos eles t?m quase a mesma largura, por diferentes gera??es. N?s tamb?m relatamos a localiza??o de modos como consequ?ncia da quase-periodicidade da heteroestrutura.Na segunda parte, investigamos os espectros de transmiss?o ?ptica para as ondas de polariza??o s (TE) e p (TM) em quasi-cristais fot?nicos unidimensionais em uma estrutura de multicamadas quase-peri?dicas composta por camadas alternadas de SiO2 e metamateriais, organizada seguindo a sequ?ncia de Octonacci. As equa??es de Maxwell e t?cnica da matriz de transfer?ncia s?o usadas para obter o espectro de transmiss?o para propaga??o de campos eletromagn?ticos incidentes normalmente e obliquamente. Assumimos a resposta dispersiva do tipo Drude-Lorentz para a permissividade diel?trica e permeabilidade magn?tica dos metamateriais. Para ondas incidentes normalmente, observamos que o espectro n?o tem comportamento auto-similar ou simetria espelho e tamb?m possui a aus?ncia de band gaps ?ptico. Tamb?m mostramos o surgimento de band gaps completos e pseudos refletores de Bragg (ou espelhos de Bragg).Na terceira e ?ltima parte, estudamos a propaga??o dos polaritons de plasmon em sistemas formados por multicamadas peri?dicas e quase-peri?dicas organizadas de acordo com a sequ?ncia de Octonacci, a partir da descri??o do comportamento dos seus modos de volume e de superf?cie. Atrav?s de c?lculo anal?tico e num?rico computacional, obtemos inicialmente os espectros de frequ?ncia dos polaritons de plasmon nestas superestruturas. Posteriormente, investigamos como a quase-periodicidade modifica a sua estrutura de bandas em rela??o ao caso peri?dico, induzindo os seus espectros a uma forma auto-similar, caracterizando a sua fractalidade/multifractalidade.