Thesis advisor: Masayuki Wasa / Thesis advisor: Amir H. Hoveyda / This dissertation describes the development of cooperative catalyst systems that contain an achiral Lewis acid and a chiral Lewis acid that may have overlapping functions but play their independent roles to promote enantioselective C–C bond formations. Chapter 1 provides a summary of recent advances made in the field of enantioselective cooperative catalysis that served as intellectual foundations for this dissertation research. As it will be discussed in the first chapter, key limitations of cooperative catalysis are: (1) undesirable catalyst deactivation which occurs due to acid/base complexation, (2) requirement for base sensitive pronucleophiles and acid sensitive electrophiles, and (3) poor reaction efficiency. In an effort to overcome these fundamental limitations, we have developed “frustrated” Lewis pair (FLP)-based catalyst systems that consist of potent and sterically encumbered Lewis acids used in pair with bulky N-containing Lewis bases. To demonstrate the potential of the novel FLP catalyst system, we describe our work involving the enantioselective Conia-ene-type cyclization (Chapter 2). In the subsequent chapter (Chapter 3), we discuss the application of the FLP catalysts for enantioselective β-amino C–H functionalization reactions. / Thesis (PhD) — Boston College, 2021. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Le trifluoroéthanol (TFE) et l'hexafluoroisopropanol (HFIP) présentent des propriétés physicochimiques particulières comme un fort pouvoir ionisant élevé, une forte capacité à donner des liaisons hydrogène, et une faible nucléophilie. Ces différentes propriétés ont été avantageusement exploitées dans plusieurs réactions sans la présence de catalyseur. Dans un premier temps, l'étude de l'amination électrophile sélective d'aromatiques avec les azodicarboxylates a été réalisée dans l'HFIP pour conduire à une famille d'hydrazines aromatiques. Ensuite l'alkylation de Friedel-Crafts avec des hétéroaromatiques et des β-nitroalcènes a conduit à des dérivées de tryptamines. Ensuite, l'halogénation sélective d'aromatiques et d'hétérocycles en présence de N-halosuccinimides (NIS, NBS et NCS) a été développée. Egalement, nous avons étudié un nouveau système combinant l'HFIP et le KHSO4 qui est un sel inorganique peu coûteux. L'association de l'HFIP et de KHSO4 (10 mol%) est un système catalytique doux et efficace pour promouvoir certaines réactions. En particulier nous avons montré que ce système catalytique a été appliqué avec succès pour l'amination directe d'aromatiques peu activés avec des azodicarboxylates pour conduire à d'autres dérivés hydrazines. Ce système a aussi montré son efficacité dans la réaction directe de benzylation de Friedel-Crafts avec des alcools benzyliques. Ainsi une grande variétés de composés diarylméthanes dissymétriques a pu être obtenue avec une excellente régiosélectivité. / Due to the electron-withdrawing character of fluoroalkyl groups, fluorinated alcohols such as trifluoroethanol (TFE) and hexafluoroisopropanol (HFIP) exhibit a nearly unique set of properties that include high ionizing power, strong hydrogen bond donating ability, mild acidity, and low nucleophilicity. All of these properties have been exploited without the need of an external catalyst. At first, the para-selective amination of free anilines with azodicarboxylates in HFIP led to hydrazine derivatives. The Friedel-Crafts alkylation of indoles and electron-rich arenes with β-nitroalkenes succeeded to afford tryptamines derivatives. Then the regioselective halogenation of arenes and heterocycles with N-halosuccinimides (NIS, NBS, NCS) have been developed. Meanwhile, we have disclosed a new mild system between HFIP and KHSO4 which is a green, inexpensive and readily available inorganic salt. The association of HFIP/KHSO4 (10 mol%) is an efficient and mild catalytic system in order to promote some reactions. In particular, we showed that this system allowed the direct amination of slightly activated and neutral arenes with azodicarboxylates in order to give other families of hydrazines. This mild system has been applied successfully for the Friedel-Crafts benzylation with benzylic alcohols. These mild conditions provided a straightforward synthesis of a variety of unsymmetrical diarylmethanes in high yield with good to high regioselectivity

Esta tesis doctoral se centra en el desarrollo de diferentes métodos electroquímicos y químicos para la funcionalización de materiales de carbono nanoestructurados, obteniendo materiales electródicos funcionales para aplicaciones bioelectroquímicas. En este sentido, las propiedades en superficie influyen directamente en la interacción entre el elemento bioreceptor o biocatalizador con el electrodo. Por tal motivo, se puede mejorar la cinética de transferencia de electrones, la inmovilización, orientación y distribución del bioelemento en el electrodo, mejorando el rendimiento del dispositivo bioelectroquímico, a partir de la química superficial del material empleado. El uso de diferentes funcionalidades de nitrógeno y fósforo generados electroquímicamente sobre los materiales de carbono nanoestructurados proporciona una plataforma para la síntesis controlada, para mejorar la actividad catalítica de biocatalizadores. Además, el proceso electroquímico de funcionalización ha demostrado ser una ruta interesante para preparar bioelectrodos en un solo paso, con bajo consumo de elementos enzimáticos y un rendimiento sobresaliente a los métodos convencionales actuales. Por otro lado, el uso de materiales de carbono dopados en N cuaternarios como elemento transductor en la síntesis de un biosensor enzimático de glucosa libre de metales proporciona, en condiciones aeróbicas, un biosensor de alta sensibilidad para la detección de glucosa en orina y bebidas azucaradas comerciales, con bajo efecto de los interferentes y alta estabilidad. Finalmente, la modificación de los nanotubos de carbono con nanopartículas de oro proporciona un material de electrodo transductor escalable y estable en el que tiene lugar la inmovilización de anticuerpos a través de interacciones Au-8. La formación de antígeno-anticuerpo complejo provoca efectos estéricos que producen un impedimento para la transferencia de electrones proveniente de una sonda redox activa hacia la superficie del electrodo, lo que facilita la detección del analito.

The reaction of base-free Chan-Lam coupling was successfully used for functionalization of surface of mesoporous silica gel. Various aromatic, aliphatic, and heterocyclic compounds were immobilized by a copper-catalyzed reaction of corresponding boronic acids with surface amino groups at mild conditions. Obtained functionalized materials were mesoporous although their surface area decreased after immobilization. The reactivity of some surface functional groups was tested in their characteristic reactions.

Orientador: Marlus Chorilli / Resumo: O câncer de próstata (CP) é a neoplasia maligna urológica mais comum e a segunda principal causa de mortalidade de homens associada ao câncer no mundo. O tratamento é iniciado por meio de intervenções cirúrgicas que abrangem a prostatectomia radical, tratamentos radioterápicos, terapias envolvendo privação androgênica e as imunoterapias. A quimioterapia também é bastante utilizada e recentes estudos demonstraram um controle notável do crescimento do CP utilizando docetaxel (DTX). No entanto, o DTX apresenta efeitos colaterais associados à toxicidade, tanto do fármaco como da formulação, Taxotere®. Em consequência disso, o desenvolvimento de sistemas nanotecnológicos de liberação de fármacos, como lipossomas, tem sido promissor para o tratamento do CP, em virtude das múltiplas características favoráveis desses nanosistemas, como biocompatibilidade e biodegradabilidade. Uma abordagem atrativa é a modificação superficial dos lipossomas com ligantes específicos dos receptores regulados nas superfícies de células tumorais, como os receptores de transferrina, que podem ser superexpressos em células tumorais de próstata. O atual trabalho visou desenvolver, caracterizar e avaliar a citotoxicidade in vitro de lipossomas funcionalizados com transferrina para veiculação do DTX no tratamento do CP. Os lipossomas foram obtidos por meio da técnica clássica da hidratação do filme lipídico e foram constituídos pela mistura de fosfatidilcolina de soja (SPC): colesterol (Col) : DSPE-PEG (2000)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Prostate cancer (PC) is the most common urological malignancy and the second leading cause of cancer-related mortality in men worldwide. Treatment is initiated through surgical interventions that include radical prostatectomy, radiotherapy treatments, androgen deprivation therapies and immunotherapies. Chemotherapy is also widely used and recent studies have shown remarkable control of CP growth using docetaxel (DTX). However, DTX has side effects associated with the toxicity of both the drug and the formulation Taxotere®. As a result, the development of nanotechnological drug delivery systems, such as liposomes, has been promising for the treatment of CP, due to the multiple favorable characteristics of these nanosystems, such as biocompatibility and biodegradability. An attractive approach is the superficial modification of liposomes with receptor-specific ligands regulated on tumor cell surfaces, such as transferrin receptors, which can be overexpressed in prostate tumor cells. The present work aimed to develop, characterize and evaluate the in vitro cytotoxicity of transferrinfunctionalized liposomes for DTX delivery in the treatment of CP. The liposomes were obtained by the classical technique of hydration of the lipid film and consisted of soybean phosphatidylcholine (SPC): cholesterol (Col): DSPE-PEG (2000) -Maleimide and SPC: Col: DSPE-PEG (2000) mixture. ) -Maleimide: DTX, in the molar ratios 10: 2: 0.78 and 10: 2: 0.78: 0.52, respectively. The characterizations were... (Complete abstract click electronic access below) / Mestre

Les recherches décrites dans ce travail appartiennent à une branche de la science relativement jeune et interdisciplinaire, la nanophotonique. Les projets réalisés avaient pour objectif de décrire les phénomènes qui apparaissent lors de l’irradiation par un faisceau lumineux d’un matériau restreint à la dimension de quelques nanomètres à quelques centaines de nanomètres. Les phénomènes qui ont été examinés sont la génération d’absorption, de dispersion et d’émission fluorescente ainsi que le renforcement d’émission fluorescente et le renforcement du champ électromagnétique à une échelle plus petite que la limite de diffraction restreignant l’optique classique. Dans cette thèse, j’ai profité de nouvelles propriétés de la matière générées quand les dimensions sont réduites à l’échelle nanométrique (10-9 m). Elles se distinguent significativement des propriétés classiques qui caractérisent un matériau de plus grandes dimensions. Le changement de propriétés résulte de la limitation spatiale de la structure du nuage d'électrons et de l’augmentation du rapport entre la surface du matériau et son épaisseur. 23 Les particules plasmoniques, largement décrites dans ce travail, en sont un excellent exemple puisque leurs colloïdes possèdent une section efficace d'absorption très importante dans le domaine visible. Un colloïde peut présenter des couleurs différentes en fonction des formes, des dimensions et de la composition des particules qui le constituent, contrairement à une surface métallique qui ne doit son aspect qu'à la réflexion presque totale de la lumière visible et au lustre métallique. À l’échelle nanométrique, nous avons affaire à la résonance plasmonique de surface, un phénomène qui ouvre la porte à la manipulation, à la modification et au renforcement du champ électromagnétique autour de la nanostructure métallique. La possibilité de concentrer la lumière autour d’une nanoparticule au-dessous de la limite de diffraction a trouvé un bon nombre d’applications, dont la microscopie en champ proche, la spectroscopie Raman exaltée de surface (ang. Surface-enhanced Raman spectroscopy, SERS), la théranostique , la production de lecteurs de carte mémoire ou de cellules photovoltaïques. Les recherches décrites dans ce travail ont un caractère interdisciplinaire, elles améliorent nos connaissances dans le domaine de la synthèse de nanostructures plasmoniques, et des méthodes de séparation permettant d'obtenir des colloïdes qui contiennent des nanoparticules presque monodispersives. La méthode de synthèse d'un nouveau métamatériau, produit lors du transfert des nanobâtonnets d’or de l’eau à l’isopropanol, a aussi été présentée dans cette thèse. Par ailleurs, ces recherches ont montré une forte exaltation du champ électromagnétique parmi les nanoparticules. J’ai aussi dénoté une application potentielle de ce matériau en tant que substrat pour la détection de biomolécules. En outre, j’ai préparé des nanocoques d’or largement stables et dont l’épaisseur de dorure est contrôlée. À l’aide de la technique Z-scan, j’ai fait la mesure des propriétés non-linéaires des nanocoques d’or et je les ai comparées avec celles des nanobâtonnets d’or et de colorants organiques en indiquant une application possible. J’ai discuté aussi d'une nouvelle méthode de biofonctionnalisation des nanobâtonnets d’or qui m’a permis de créer un marqueur afin de visualiser des cellules vivantes. Il est aussi possible de convertir l’énergie lumineuse en énergie thermique par le biais des nanostructures plasmoniques, ce qui pourrait trouver d’autres applications intéressantes dans les recherches en théranostique. / This dissertation shows the experimental results, which I strongly believe prove the possibility of application the proposed bioprobe in theranostics treatment. The advantages and disadvantages of the probe were discussed on the basis of imaging of cancer cells, toxicity and fluorescent efficiency. It is important to mention that the process of synthesis of the biomarker was controlled on each step, starting from the selection of appropriate size and shape of the core, through optical characterization, effective way of biofunctionalization and finally application in cell visualization.At first, I presented an improved method of separation of distinct shapes of gold nanoparticles from a heterogeneous mixture. The method of centrifugation in a glucose density gradient was applied in order to get homogenous fractions. The procedure of sample preparation, centrifugation and collection of the separated nanoparticles is described. Moreover, I discussed the synthesis with and without Ag+ ions added to the growth solution.Then, I had a closer look on transferring procedure of the NRs from water into IPA solvent, which induce self-organization of the nanoparticles. Optical characterization as well as recorded ATR spectra gave the foundations to understanding of the assembly process taking place. Additionally the work is enriched with the theoretical calculations indicating that individual self-assembled nanostructures show strong light polarization dependent properties. The electric field localized in the gap between NRs is estimated to be enhanced over 350 fold.In the next part of my thesis I have performed a systematic and quantitative description of the interactions of NRs with light (femtosecond laser pulses, 130 fs, 800 nm) in order to characterize the optical properties and design NRs with specific functionalities. In this work I focused on the investigation of structural changes of the NRs and the parameters influencing the reshaping, like surface modification using sodium sulfide, laser power and the position of the longitudinal surface plasmon resonance band (l-SPR) with respect to the laser wavelength.In the next part of the thesis I have quantified the probability of simultaneous absorption of two photons by plasmonic nanoparticles: gold nanorods and gold nanoshells, and by several dye molecules, by using the open-aperture Z-scan technique available in the laboratory at WUT in Poland. At first, I started from fabrication of stable and highly monodisperse NSs suspensions in water, with a varying degree of gold coverage. Then, the NLO properties of the nanoshells were quantified in terms of the two-photon absorption coefficient (α2), the nonlinear refractive index (n2), and the saturation intensity for one-photon absorption (Isat), which are extensive quantities. Then I calculated the two-photon absorption cross-section (σ2) taken per nanoparticle, which was also interpreted in terms of the merit factor σ2/M (where M is the molar mass of the nanoparticle), the quantity suitable for comparisons with other types of nonlinear absorbers.Finally, in the last chapter I have combined the results and knowledge from all previously described experiments in order to propose a new bioprobe. The probe is based on NR functionalized by DNA strand with attached fluorophore. The distance between gold surface and dye is selected in a such way as to maximize the fluorescent emission. The viability tests show low toxicity for cells and high compatibility. I showed that biofunctionalized NRs can provide fluorescent labeling of cancer cells and enable effective photothermal therapy. This is one of the first demonstrations of coupling a bioimaging application to a cancer therapy application using NRs targeted against a clinical relevant biomarker. I hope that the future studies will extend the in vitro concept demonstrated here to in vivo animal experiments.

abstract: Layered chalcogenides are a diverse class of crystalline materials that consist of covalently bound building blocks held together by van der Waals forces, including the transition metal dichalcogenides (TMDCs) and the pnictogen chalcogenides (PCs) among all. These materials, in particular, MoS2 which is the most widely studied TMDC material, have attracted significant attention in recent years due to their unique physical, electronic, optical, and chemical properties that depend on the number of layers. Due to their high aspect ratios and extreme thinness, 2D materials are sensitive to modifications via chemistry on their surfaces. For instance, covalent functionalization can be used to robustly modify the electronic properties of 2D materials, and can also be used to attach other materials or structures. Metal adsorption on the surfaces of 2D materials can also tune their electronic structures, and can be used as a strategy for removing metal contaminants from water. Thus, there are many opportunities for studying the fundamental surface interactions of 2D materials and in particular the TMDCs and PCs. The work reported in this dissertation represents detailed fundamental studies of the covalent functionalization and metal adsorption behavior of layered chalcogenides, which are two significant aspects of the surface interactions of 2D materials. First, we demonstrate that both the Freundlich and Temkin isotherm models, and the pseudo-second-order reaction kinetics model are good descriptors of the reaction due to the energetically inhomogeneous surface MoS2 and the indirect adsorbate-adsorbate interactions from previously attached nitrophenyl (NP) groups. Second, the covalent functionalization using aryl diazonium salts is extended to nanosheets of other representative TMDC materials MoSe2, WS2, and WSe2, and of the representative PC materials Bi2S3 and Sb2S3, demonstrated using atomic force microscopy (AFM) imaging and Fourier transform infrared spectroscopy (FTIR). Finally, using AFM and X-ray photoelectron spectroscopy (XPS), it is shown that Pb, Cd Zn and Co form nanoclusters on the MoS2 surface without affecting the structure of the MoS2 itself. The metals can also be thermally desorbed from MoS2, thus suggesting a potential application as a reusable water purification technology. / Dissertation/Thesis / Doctoral Dissertation Materials Science and Engineering 2019

Les attentes autour du graphene peuvent être expliquées par les fortes potentialités applicatives de ce matériau (transistors RF, (bio)capteurs, TCL…). Sa grande surface spécifique, sa forte résistance mécanique ainsi que sa bonne conductivité permettraient de cibler des applications dans le domaine du stockage électrochimique tel que les pseudo-condensateurs. Il a été mis en évidence que des structures 3D de graphène définies comme des hydro- ou des aero- gels et présentant des surfaces spécifiques très élevées peuvent être obtenues. Ce type d’architecture présente un fort potentiel dans le domaine des matériaux d’électrodes carbonées pour le stockage de l’énergie et notamment pour les super-condensateurs. Leur obtention repose soit sur l’utilisation de molécules pontantes et de la création d’interactions covalentes ou électrostatiques, soit sur la réalisation d’aérogel à partir d’oxyde de graphène dans des conditions de pression/température établies. Basé sur ce contexte, le sujet de thèse présenté propose de développer des matériaux structurés à base de graphene (Fig.) pouvant être utilisés pour des applications en stockage électrochimique. La grande surface spécifique ainsi que la bonne conductivité du graphène permettraient de cibler de hautes densités d’énergie et de fortes puissances. Les différentes méthodes de préparation de ces architectures aérogels seront testées et les matériaux obtenus seront caractérisés morphologiquement (MEB, TEM, BET), structurellement (DRX) et chimiquement (XPS, IR, Raman, ATG). Les propriétés électrochimiques de ces espèces - correspondant à de nouvelles formes de carbones nanoporeux - seront ensuite évaluées. Ces structures seront également fonctionnalisées pour favoriser la formation d’une SEI stable et l’intercalation de certains ions. L’immobilisation de composés redox actifs sera testée afin d’insérer une composante pseudocapacitive au système. Les performances de ces matrices modifiées - s’apparentant à des matériaux d’électrodes pour pseudo-supercondensateur - seront enfin analysées. Les tâches que le thésard réalisera au cours de sa thèse seront donc variées et iront de la fabrication du matériau de base jusqu’à l’évaluation de son utilisation en cellule électrochimique. / The expectations around graphene come from huge potentialities for various applications (RF transistor, (bio)sensors…). Graphene high specific surface, mechanical resistance and conductivity make it specifically attractive for electrochemical storage applications. It has been shown that graphene sheets could be assembled to form structured graphene frameworks to translate the properties of individual sheets to functional materials and allow practical applications. The key features of these frameworks in terms of electrochemical storage applications are their graphitization level, their structural or textural disorder, and their porosity. On another hand, graphene has been interfaced with molecules to tune its electrical/optical properties or to make it more processable. The goal of the PhD project is to develop such structured graphene matrices following different methods such as the functionalization with bi-functional pilar molecules or the aerogel formation techniques. These assemblies will then be modified with different molecules to favor the formation of a stable SEI (solid electrolyte interface) and the intercalation of ions. The immobilization of redox compounds will also be attempted in order to bring a pseudo capacitive component to the system and target pseudo-capacitor applications. This thesis work will include material synthesis, assembling and functionalization steps combined to an important characterization tasks (IR, XRD, XPS, MEB, TEM, BET, electrochemistry...) The added-value of such work is that it represents an approach going from the basic material develop to the proof of concept.

No description available.

No description available.