In the onset of many chronic illnesses including Parkinson’s, Alzheimer’s, and cardiovascular diseases, there is evidence to support the delicate balance between prooxidant and antioxidant species is shifted in favor of the former. Under these conditions, many reactive oxygen species (ROS) including hydroxyl radicals, are generated. Hydroxyl radicals formed in close proximity to DNA, nucleotides, proteins, and lipids rapidly oxidize these biological molecules in a nonspecific way. However, their toxicity is limited by their short lifetimes. Currently, the mechanism by which hydroxyl radicals are involved in the onset of many illnesses, particularly with regard to lipid peroxidation, has yielded some controversy in the literature. Conventional studies which generate hydroxyl radicals with Fenton chemistry through bolus additions of iron and hydrogen peroxide do not mimic conditions found physiologically because there is a steady-state concentration of hydrogen peroxide concentration found in normal cellular systems. Also, former reports that used fluorescent fatty acids or free probes intercalated within liposomal membranes did not have the probes covalently attached to the phospholipids making up the liposomes. Thus, the actual placement of the probes over the analysis time may vary with experimental conditions. The objective of this research project was to prepare, characterize, and employ liposomes as models for cell membranes during free radical oxidation. Also, compared to the popularly-used technique of electron spin resonance, (ESR), our aim was to use a fluorescence-based approach which yielded the advantages of high sensitivity, fast analysis time, and less expensive equipment requirements. Degradation of fluorescently-tagged liposomes with probes covalently bound to the phospholipids was correlated with the ability of hydroxyl radicals and other possible reactive oxygen species to penetrate into the liposomes to deeper into the lipophilic layer. However, alone this experimental setup may not fully define the mechanistic role of hydroxyl radicals in lipid oxidation. Thus, a complementary approach embracing the use of MALDI-TOF mass spectrometry, lipophilic scavenger studies, and the effects of cholesterol and temperature allow a deeper understanding of the radically-driven oxidation of lipids. It was determined that hydroxyl radicals were generated and reacted with three fluorescent probes.

Se recolectó información completa de 188 pacientes con diagnóstico y tratamiento de cáncer de mama estadio I-II durante el año 2007 y con seguimiento por 5 años, atendidas en el Hospital Edgardo Rebagliatti Martins. 106 (56,4%) pacientes fueron sometidas a mastectomía radical modificada (MRM) y 82 (43,6%) de pacientes, fueron sometidas a tumorectomía más evaluación del ganglio centinela (EGC) como paso previo a una potencial disección de axila. Hubo una mayor tendencia de asignar una estrategia quirúrgica radical a las pacientes con un estadío clínico más severo. Así, 16 (28,6%) de pacientes en estadio I fue sometida a MRM y 40 (71,4%) de pacientes en estadío I fueron sometidas a manejo con ganglio Centinela. En el estadío IIA, se encontró que 59 (67,8%) de pacientes fueron sometidas a Mastectomía Radical Modificada y que 28 (32,2%) de pacientes fueron sometidas a Manejo con ganglio centinela. En el estadío IIB, se encontró que 31 (68,9%) pacientes fueron sometidas a Mastectomía radical modificada y 14 (31,1%) pacientes fueron sometidas a manejo con ganglio centinela. El estadio clínico fue identificado como estadio I en 56 (29,8%) pacientes, estadio IIA en 87 (46,3%) pacientes y el estadio IIB en 45 (23,9%) pacientes. Al interior de las pacientes con estadío clínico II, la subdivisión en IIA y IIB, no implicó mayor variación en la asignación de la estrategia quirúrgica. Entre las 82 pacientes sometidas al tratamiento quirúrgico conservador, 18 (28.1%) de ellas tuvieron ganglio centinela positivo lo que obligo a una disección de axila. Visto de otra forma se intento evitar la mastectomía radical modificada en 82 pacientes, pero se tuvo que llegar a la disección de axila en 18 de ellas. De manera que la reducción de potenciales MRM o disecciones de axila fue del orden del 72.

Au coeur de la présente thèse se trouve la quête inachevée d’une/de conscience(s) de libération au moyen d’une pensée radicale et critique. Le savoir épistémologique développé par bell hooks et Paulo Freire quant à la transformation de conscience en vue d’une libération a été le premier guide dans cette recherche. L’étude empirique exprime ce que signifie une trans/formation de conscience politique, pour les participant.e.s – plusieurs acteur.e.s politiques palestinien.ne.s et israélien.ne.s situé.e.s à l’intérieur des frontières géographiques de l’Etat d’Israël. À travers de longs entretiens sous la forme de conversations, cette recherche ambitionne de comprendre les voies biographiques qui conduisent les participant.e.s à opérer des performances contre-hégémoniques dans leur vie quotidienne. La conscience coloniale est en rapport avec des questions de savoir et de pouvoir et est liée, d’après les participant.e.s, à une position hégémonique de pouvoir, de violence et d’arrogance. Cette recherche montre que si le sionisme est défini par tou.te.s les participant.e.s comme un fondement de l’oppression et de la domination institutionnalisées, il ne détermine pas de la même manière le destin des participant.e.s juif.ve.s israélien.ne.s ashkénazes, juif.ve.s israélien.ne.s mizrahi.e.s et palestinien.ne.s. L’engagement dans les processus de trans/formation est perçu comme l’accès à un site inconnu de transgression où l’on acquiert du savoir et des outils tout au long du voyage. La vue apparaît comme un sens crucial à travers lequel les participant.e.s racontent la perpétuation de la conscience coloniale ainsi que la possibilité de développer un regard contre-hégémonique libérateur. Les récits de libération des participant.e.s impliquent une pensée critique suivie, qui examine constamment la réalité et dévoile la vérité sur le monde. De même, il semble que tou.te.s les participant.e.s, tout en se trouvant à différentes étapes de leur processus de libération, comprennent la trans/formation de leur conscience politique, et ainsi leur quête de libération des structures coloniales de la pensée, comme une quête de savoir objectif authentiquement féministe. Les récits montrent que le fait d’abandonner des positions binaires permet une compréhension complexe de la réalité et du propre point de vue du sujet dans cette réalité, et est essentiel pour le(s) processus de libération. Les deux premiers chapitres, qui composent la première section intitulée « Le Regard », décrivent ce que signifie la conscience coloniale pour les participant.e.s, puis tracent les contours du processus de libération et présentent la réalité asymétrique d’un point de vue national. Avec le développement d’une lecture complexe de la colonialité israélienne, la thèse poursuit une analyse à plusieurs facettes. C’est ce qui est présenté dans la deuxième section, intitulée « Acte(s) de libération : faire de la pensée critique », où sont présentés les actes et les tâches assumées dans la quête d’une libération continue. Au troisième chapitre, sous le titre « Rendre présent » et au quatrième,intitulée « Rencontres radicales », est présentée la manière dont le développement d’un regard oppositionnel implique une constante réflexivité quant à la propre position du sujet au sein des rapports de pouvoir. Comment la conscience coloniale peut-elle être défaite au sein de la structure israélienne de colonialité ? Comment peut-on se frayer un chemin vers des manières alternatives de vivre ensemble ? Ces questions et d’autres, tout aussi vitales, sont au fondement du présent travail. / At the center of this dissertation stands the unending quest for liberation consciousness(es) through radical and critical thought. The epistemological knowledge developed by bell hooksand Paulo Freire, on consciousness transformation towards liberation has been the primary guide in this research. The empirical study expresses what trans/formation of political consciousness means to these participants - several Palestinian and Jewish-Israeli political actors with in the geographical boundaries of the State of Israel. Through long conversational interviews, the research strives to understand the biographical paths which lead the participants to counter-hegemonic performances in their daily life. Colonial consciousness relates to questions both of knowledge and of power and is connected, according to the participants, to a hegemonic position of power, violence and arrogance. The research has shown that while Zionism is defined by all participants as a basisto oppression and to institutionalized domination, it does not determine the fate of the Ashkenazi Jewish-Israelis, the Mizrahi Jewish-Israelis and Palestinian participants in the same way. To engage in liberation trans/formation processes was perceived as an entranceinto an unknown site of transgression from which one acquires knowledge and tools throughout the journey. Vision appears to be a crucial sense through which the participants recount the perpetuation of colonial consciousness, as well as the possibility to develop acounter-hegemonic gaze, which liberates.The participants’ accounts of liberation entail ongoing critical thought that constantly examines reality and unveils the truth about the world. Likewise, it seems that all participants, while in different stages within their processes of liberation, understand the trans/formation of their political consciousness and thus their quest for liberation from colonial structures of thought as a quest for genuine feminist objective knowledge.The accounts have shown that stepping out of binary positions, enables a complex understanding of reality and of one’s own standpoint within it, and are crucial within liberation processes(es). The two first chapters, which comprise the first station called The Gaze, describe what colonial consciousness means to the participants and then outlines the process of liberation, and presents the asymmetric reality from a national standpoint. With the development of a complex reading of Israeli coloniality, the dissertation follows a more multifaceted analysis. It is presented in the second station, called, Act(s) of Liberation : “Doing Critical Thinking”, and presents the acts and tasks one takes in the quest for constant liberation. In Chapter Three, entitled ‘Presencing’ and Chapter Four, entitled, ‘Radical Encounters’ I present the way the development of an oppositional gaze entails constant self reflexivity on one’s own position within the relations of power. How can colonialconsciousness be undone within the Israeli structure of coloniality ? How can people work their way towards alternative ways of living together ? These questions and some other vital ones, are at the basis of this work.

Ultrasound irradiation of a protein or polymer solution at the air:water interface can be used to form hollow microspheres containing an air bubble. By introducing a layer of oil and sonicating the oil:water interface, microspheres containing an oil droplet are formed. The microspheres are stabilised by disulfide crosslinking, have diameters of between 1-20 mm and have a number of applications; gas filled protein microspheres are used as ultrasound contrast agents and oil filled microspheres are being developed for delivery of lipophilic drugs. This project extends the scope of sonochemically produced microspheres to include water-in-oil emulsion filled microspheres, which facilitate encapsulation of hydrophilic species, and polymer microspheres that release their contents in response to an external stimulus. Successful encapsulation of a water in oil emulsion phase is demonstrated using confocal microscopy. Release studies are reported for a number of hydrophilic species (in vitro) including 5,6-carboxyfluorescein, 5-fluorouracil and sodium chloride. Release can be triggered by sonochemical disruption of the microsphere shells or cleavage of the disulfide cross links. Thiol-ene coupling reactions initiated by ultrasound irradiation are reported. In water, ultrasound initiation of thiol-ene reactions with electron rich alkenes results in rates of reaction which compare favourably with conventional thermal initiation. Thiol-ene crosslinking is proposed as an alternative to disulfide crosslinking to stabilise sonochemically produced microspheres. Temperature responsive microspheres are produced via the sonochemical method using a block copolymer of N-isopropylacrylamide and thiolated methacrylic acid, P(MASH-b-NIPAm). The block co-polymer is synthesised using reversible addition-fragmentation transfer (RAFT) polymerisation and has a lower critical solution temperature (LCST) of 37 ºC. The microspheres formed from this block copolymer can be seen to rupture, releasing their internal oil phase, when heated above 37 ºC. These findings provide a basis from which to develop sonochemically produced polymer microspheres for responsive delivery of both hydrophilic and lipophilic species.

The following thesis outlines work carried out during the past three years for the discovery and investigation of catalytic methodologies towards the synthesis and modification of heterocycles, namely cyclic carbamates, carbonates and their sulfur analogues. Chapter 1 summarises the current catalytic methods reported in the literature towards the synthesis and modification of functionalized 2-oxazolidinones. This introduction highlights the diverse range of methods and catalysts that have been developed and their scope and limitations. In addition the review highlights the importance of these structural motifs and suggests areas in which the following research fulfills unmet needs. Chapter 2 reports the discovery and development of a one-pot two-step copper-catalysed methodology towards the synthesis of N-aryl oxazolidinones from amino alcohol carbamates. The scope of both the N-aryl substituent as well as oxazolidinone functionalization is presented in addition to preliminary investigations into the mechanisms of both reactions. Chapter 3 presents the application of the previously reported one-pot process towards the synthesis of a number of medicinally active molecules and blockbuster pharmaceuticals. The one-pot two-step copper-catalysed reaction was utilized to synthesise a common intermediate in the synthesis of a number of oxazolidinone-based pharmaceuticals. The complete syntheses of Toloxatone, Linezolid, Tedizolid and Rivaroxaban are reported. Chapter 4 reports the modification of N-aryl oxazolidinones towards a diverse library of N-aryl oxazolidinethiones. The reactivity of these structures, in addition to N-alkyl oxazolidinethiones, towards transition metal catalysis was investigated and revealed a ruthenium catalysed O- to S-alkyl migration to afford structurally diverse thiazolidinones. Investigations into the substrate scope and mechanism were also carried out, suggesting a pseudo-reversible radical pathway drawing mechanistic parallels to the classic Barton-McCombie reaction. Chapter 5 details further development of the pseudo-reversible radical pathway for the regioselective rearrangement of dioxolane-2-thiones using Pd(PPh3)4 as a catalyst. The scope of the reaction is reported for the formation of highly selective, highly substituted sulfur-rearrangement products.

This work reports the investigation of Cu-mediated polymerization systems and its limits, in order to obtain functional branched polymers, in particular star-shaped and graft-shaped polymers. A novel initiator structure has allowed developing a new approach to synthesise sequence controlled multiblock star polymers via Cu-mediated reversible deactivation radical polymerization (RDRP) in water. This technique allows the preparation of pentablock star shaped polymers in just under 90 minutes of reaction time. The obtained polymers had a good agreement between theoretical and experimental molecular weights and excellent control over molecular weight distribution. Alternatively, the Cu-mediated RDRP of star polymers using a British 1 penny coin was described, displaying similar results as in the literature, providing better experimental conditions. As the copper coin was recovered unharmed, the catalyst was found to be economically very effective. Furthermore, poly(2-ethyl oxazoline) (PEtOx) was polymerized with good control and partially hydrolysed to poly(ethylene imine) (PEI) to yield PEtOx-r-PEI using a microwave reactor. The secondary amines of PEI was converted to macroinitiators, to allow the polymerization of acrylamides in aqueous medium, resulting in graft type polymers based on a poly(oxazoline) backbone with acrylamide side chains. Finally, the synthesis of carbohydrate-monomers was described, which allows to obtain monomers with a different number of carbohydrates (one, two or three). These monomers were polymerised via aqueous SET-LRP, to explore their interaction with carbohydrate binding lectins and to understand the impact on binding of carbohydrate density on polymers and polymer chain length.

Iron-catalysed carbonyl reduction, nitro reduction, formal hydroamination, and the radical alkenylation of alkyl halides have been developed. A Simple, easy-to-make, air- and moisture-stable iron(III) amine-bis(phenolate) complex catalysed the hydrosilylation of carbonyl compounds efficiently using triethoxysilane as the reducing agent. The reaction tolerated a wide range of substrates to give the corresponding alcohol products in good to excellent yields after hydrolysis of the hydrosilylated products (Scheme A1). Scheme A1. Iron-Catalysed Hydrosilylation of Carbonyl Compounds. The same catalyst was also an active catalyst for the chemoselective reduction of nitro arenes into corresponding amines using triethoxysilane as reducing agent. The method exhibited excellent chemoselectivity as other reducible functional groups such as halogen, ester, nitrile all kept unchanged during the reaction. This catalytic system was then successfully applied to the formal hydroamination of alkene to give substituted amine in synthetic useful yields under mild condition. The reaction is hypothesised to proceed through a radical intermediate (Scheme A2). Scheme A2. Iron-Catalysed Nitro Reduction and Alkene Formal Hydroamination. Finally, FeCl2-catalysed formal Heck cross-coupling has been developed between alkyl halides and styrenes. The reaction tolerated both electron-rich and electron-neutral substrates to give the products in moderate to excellent yields. Initial studies revealed that the reaction also proceeds through a radical intermediate (Scheme A3). Scheme A3. Iron-Catalysed Formal Heck Cross-Coupling of Functionalised Alkyl Halides.

We report a novel fragmentation and functionalization method using a cyclic iminyl radical. Formation of this radical occurs by microwave heating under mild conditions and short reaction times. The reaction avoids the use of explosive or toxic radical initiators and propagating agents. This reaction is versatile, with the ability to install two functional groups that are ultimately derived from a ketone in the substrate precursor. A variety of radical traps capable of forming both carbon-carbon bonds and carbon-heteroatom bonds have been tested, and the products are obtained in good yields. We demonstrate the power of this reaction by functionalizing complex natural products.

An experimental approach was taken in determining the quantum yield of Ruthenium(II) with Oxygen using two different Ru complexes. This reaction results in Ruthenium(III) and O2-. The Coulombic interactions caused by a carboxylate functional was found to increase the yield of charge separation. This was done using a diode to measure the intensity of the completed reaction over a certain time frame. The intensities were turned into concentrations. The concentration over time was used to determine the quantum yield. This information is useful in creating more efficient light emitting diodes.

The main purpose of this paper is to examine the road towards the structure of simple and semi-simple Artinian rings. We refer to these structure theorems as the Wedderburn-Artin theorems. On this journey, we will discuss R-modules, the Jacobson radical, Artinian rings, nilpotency, idempotency, and more. Once we reach our destination, we will examine some implications of these theorems. As a fair warning, no ring will be assumed to be commutative, or to have unity. On that note, the reader should be familiar with the basic findings from Group Theory and Ring Theory.