Atom transfer radical polymerization (ATRP) is one of the most commonly employed techniques for controlled radical polymerization. ATRP has great potential for the development of new materials due to the ability to control molecular weight and polymer architecture. To fully utilize the potential of ATRP as polymerization technique, the mechanism and the dynamics of the ATRP equilibrium must be well understood. In this thesis, various aspects of the ATRP process are explored through both laboratory experiments and computer modeling. Solvent effects, the limit of control and the use of iron as the mediator have been investigated. It was shown for copper mediated ATRP that the redox properties of the mediator and the polymerization properties were significantly affected by the solvent. As expected, the apparent rate constant (kpapp) increased with increasing activity of the mediator, but an upper limit was reached, where after kpapp was practically independent of the mediator potential. The degree of control deteriorated as the limit was approached. In the simulations, which were based on the thermodynamic properties of the ATRP equilibrium, the same trend of increasing kpapp with increasing mediator activity was seen and a maximum was also reached. The simulation results could be used to describe the limit of control. The maximum equilibrium constant for controlled ATRP was correlated to the propagation rate constant, which enables the design of controlled ATRP systems. Using iron compounds instead of copper compounds as mediators in ATRP is attractive from environmental aspects. Two systems with iron were investigated. Firstly, iron/EDTA was investigated as mediator as its redox properties are within a suitable range for controlled ATRP. The polymerization of styrene was heterogeneous, where the rate limiting step is the adsorption of the dormant species to the mediator surface. The polymerizations were not controlled and it is possible that they had some cationic character. In the second iron system, the intention was to investigate how different ligands affect the properties of an ATRP system with iron. Due to competitive coordination of the solvent, DMF, the redox and polymeri­zation properties were not significantly affected by the ligands. The differences between normal and reverse ATRP of MMA, such as the degree of control, were the result of different FeIII speciation in the two systems. / QC 20110406

A series of 1,2,3-dithiazolyl radicals have been prepared as spin-bearing radical ligands for coordination to paramagnetic transition metal and lanthanide ions to afford both interesting magnetic and potential conductive properties. The novel syntheses and full characterization of the ligands are described with the electronic properties investigated by both solution & solid-state EPR and cyclic voltammetry. The ligand structures are characterized by X-ray crystallography and the magnetic properties investigated. The ligands described herein represent the first reported 1,2,3-dithiazolyl radical ligands to coordinate to paramagnetic transition metal or lanthanide ion(s). The 1,2,3-dithiazoyl ligands described have been used to prepare a number of metal complexes and the structures have been fully characterized by X-ray crystallography. A diverse range of complexes including monomers, trimers and polymers have been synthesized and characterized. The solid-state and solution magnetic properties of the metal complexes have been investigated using a range of appropriate instrumental techniques, and are reported. The chelating properties of the 1,2,3-dithiazolyl ligands described are via an unprecedented motif. A para-naphthoquinone backbone is utilized with the fused 1,2,3dithiazolyl heterocyclic ring. The coordination geometry between the nitrogen atom and the quinone oxygen(s) allows for the variety of complexes reported, including the design objective of a polymeric paramagnetic coordination complex. A series of 1,2,5-thiadiazolyl radical anions have been prepared as spin-bearing radical ligands for the coordination to paramagnetic transition metal and lanthanide ions to enable both interesting magnetic and conductive properties. The syntheses and full characterizations are described with the electronic properties investigated by solution EPR and cyclic voltammetry. The ligand structures are characterized by X-ray crystallography and both the magnetic properties and conductivity (including Extended Hückel Theory calculations) are investigated and reported. A series of novel fluorinated 1,2,5-thiadiazole closed shell neutral ligands have been prepared and characterized. The radical anion is studied in situ by EPR. All materials generated in the synthesis were sent to the National Cancer Institute (USA) for collaboration involving clinical cancer inhibition studies and the results are reported.

Verdazyl radicals are a family of multicoloured stable free radicals. Aside from the defining backbone of four nitrogen atoms, these radicals contain multiple highly modifiable sites that grant them a high degree of derivatization. Despite having been discovered more than half a century ago, limited applications have been found for the verdazyl radicals and little is known about their chemistry. This thesis begins with an investigation to determine whether verdazyl radicals have a future as mediating agents in living radical polymerizations and progresses to their application as substrates for organic synthesis, an application that to date has not been pursued either with verdazyl or nitroxide stable radicals. The first part of this thesis describes the successful use of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical as a mediating agent for styrene and n-butyl acrylate stable free radical polymerizations. The study of other verdazyl derivatives demonstrated the impact of steric and electronic properties of the verdazyl radicals on their ability to mediate polymerizations. The second part of this thesis outlines the initial discovery and the mechanistic elucidation of the transformation of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical into an azomethine imine, which in the presence of dipolarophiles, undergoes a [3+2] 1,3-dipolar cycloaddition reaction to yield unique pyrazolotetrazinone structures. The reactivity of the azomethine imine and the scope of the reaction were also examined. The third part of this thesis describes the discovery and mechanistic determination of a base-induced rearrangement reaction that transforms the verdazyl-derived pyrazolotetrazinone cycloadducts into corresponding pyrazolotriazinones or triazole structures. The nucleophilicity, or the lack thereof, of the base employed leading to various rearrangement products was examined in detail. The final part of this thesis demonstrates the compatibility of the verdazyl-initiated cycloaddition and rearrangement reactions with the philosophy of diversity-oriented synthesis in generating libraries of heterocycles. A library of verdazyl-derived heterocycles was generated in a short amount of time and was tested non-specifically for biological activity against acute myeloid leukemia and multiple myeloma cell lines. One particular compound showed cell-killing activity at the 250 mM range, indicating future potential for this chemistry in the field of drug discovery.

Verdazyl radicals are a family of multicoloured stable free radicals. Aside from the defining backbone of four nitrogen atoms, these radicals contain multiple highly modifiable sites that grant them a high degree of derivatization. Despite having been discovered more than half a century ago, limited applications have been found for the verdazyl radicals and little is known about their chemistry. This thesis begins with an investigation to determine whether verdazyl radicals have a future as mediating agents in living radical polymerizations and progresses to their application as substrates for organic synthesis, an application that to date has not been pursued either with verdazyl or nitroxide stable radicals. The first part of this thesis describes the successful use of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical as a mediating agent for styrene and n-butyl acrylate stable free radical polymerizations. The study of other verdazyl derivatives demonstrated the impact of steric and electronic properties of the verdazyl radicals on their ability to mediate polymerizations. The second part of this thesis outlines the initial discovery and the mechanistic elucidation of the transformation of the 1,5-dimethyl-3-phenyl-6-oxoverdazyl radical into an azomethine imine, which in the presence of dipolarophiles, undergoes a [3+2] 1,3-dipolar cycloaddition reaction to yield unique pyrazolotetrazinone structures. The reactivity of the azomethine imine and the scope of the reaction were also examined. The third part of this thesis describes the discovery and mechanistic determination of a base-induced rearrangement reaction that transforms the verdazyl-derived pyrazolotetrazinone cycloadducts into corresponding pyrazolotriazinones or triazole structures. The nucleophilicity, or the lack thereof, of the base employed leading to various rearrangement products was examined in detail. The final part of this thesis demonstrates the compatibility of the verdazyl-initiated cycloaddition and rearrangement reactions with the philosophy of diversity-oriented synthesis in generating libraries of heterocycles. A library of verdazyl-derived heterocycles was generated in a short amount of time and was tested non-specifically for biological activity against acute myeloid leukemia and multiple myeloma cell lines. One particular compound showed cell-killing activity at the 250 mM range, indicating future potential for this chemistry in the field of drug discovery.

The use of hydroxyl radical based reaction (Fenton reaction) for the destruction of organic pollutants has been widely reported in the literature. However, the low pH requirement and rapid hydrogen peroxide consumption rate make the application of conventional Fenton reaction difficult for in-situ treatment. In this study, we conducted a modified Fenton reaction by introducing a chelating agent into the reaction system that could prevent Fe(OH)3 (s) precipitation even at a neutral pH condition and reduce the H2O2 consumption rate by controlling the Fe2+ concentration. A chelating agent (mono-chelate or poly-chelate) combines with Fe2+ or Fe3+ to form stable metal-chelate complexes in solution. This decreases the concentration of Fe2+ in the solution so that reactions can be carried for longer contact times. Experimental results (citrate was the chelating agent) for 2,4,6-trichlorophenol (TCP) showed that TCP degradations were greater than 95% after 2.5 h and 24 h reaction times at fixed pH 5 and 6, respectively. For the same reaction time, the normalized chloride formations were 85% at pH 5 and 88% at pH 6. Several other chlorinated organic compounds were also chosen as the model compounds for detoxification studies because of their chemical structures: trichloroethylene (unsaturated hydrocarbon), carbon tetrachloride (highly oxidized compound), 2,2-dichlorobiphenyl, and biphenyl (a dual-aromatic ring structure). Poly-chelating agents (such as polyacrylic acid-PAA) provide multiple Fe2+/Fe3+ binding sites in the modified Fenton reaction for the oxidation of contaminants (2,2-dichlorobiphenyl, and biphenyl) at a neutral pH environment. Numerical simulation based on the kinetic model developed from the well known Fenton reaction and iron-chelate chemistry fits experiment data well for both standard and chelate modified Fenton reactions. In this dissertation, it was proven that both monomeric (citrate) and polymeric (PAA) chelate modified Fenton reactions were effective for dechlorination of carbon tetrachloride from aqueous phase by the superoxide radical anion. On the other hand, PAA (a poly-chelating agent) can also be used for solid surface modification by polymerization of acrylic acid (monomer). The successful degradations of biphenyl and trichloroethylene by the PAA functionalized silica particles/membrane demonstrate the versatile applications of the chelate modified Fenton reaction.

The aim of this work was to successfully prepare polymers of N-(2-hydroxypropyl)methacrylamide, (PHPMA) using controlled/"living" free-radical polymerisation technique. For this purpose, atom transfer radical polymerisation (ATRP) and reversible addition-fragmentation (chain) transfer (RAFT) polymerisation were used in preparation of a number of base polymers with the intention of quantitatively converting them into PHPMA. Both methods were applied under varying polymerisation conditions, and the kinetics of the systems investigated. Various rate constants were measured, while computer modelling of the experimental data allowed estimation of other kinetic parameters of interest. Investigations into solvent and ligand effects on the kinetics of ATRP of the activated ester methacryloyloxy succinimide (MAOS) and one of the archetypal methacrylate monomers, methyl methacrylate (MMA) were carried out. The method of RAFT was also employed in polymerisation of MAOS and a number of other monomers in the hope of finding the best synthetic precursor of PHPMA. Polymers of methacryloyl chloride (MAC) and p-nitrophenyl methacrylate (NPMA) were prepared, as well as the polymers of HPMA itself and N-isopropyl methacrylamide. Polymerisation of MMA by RAFT was also attempted in view of adding to current knowledge on the monomer's behaviour and the kinetic characteristics of its RAFT polymerisation. Preparation of PHPMA from PMAOS, PMAC and PNPMA was attempted. Successful preparation of PHPMA from the polymer of the acid chloride was achieved under mild reaction conditions, while displacement of N-hydroxysuccinimide groups of PMAOS resulted in unexpected modification of the polymer under the conditions used. Conversion of PNPMA into PHPMA was not achieved. At this stage these results suggest inadequacy of both PMAOS and PNPMA as reactive polymeric precursors.

Aerosols of nitrate solutions were irradiated in the presence of radical scavengers in an attempt to measure the yield of hydroxyl radical in both the aqueous phase and the gas phase. Carbon monoxide, benzoic acid, benzene and cyclohexane were used as scavengers to trap hydroxyl radical. The products from the reaction of these scavengers with hydroxyl radical were analysed with High Performance Liquid Chromatography and mass spectrometry. The radiant flux in the chamber was measured via ferrioxalate actinometry, both with bulk liquid and aerosol droplets. Many quantitative results were obtained but several anomalies were found. This suggests that Mie theory is not capable of predicting rates of photochemical reactions within droplets.

Orientador: Hamilto Akihissa Yamamoto / Resumo: Proposta: O câncer de próstata é o tumor sólido mais comum em homens. A prostatectomia radical é importante forma curativa dessa doença, mas tem como uma das complicações mais temidas a disfunção erétil. Estudos prévios demonstram ação da fisioterapia como forma de tratamento dessa complicação, mas sua real importância ainda está por ser definida. Neste artigo foi proposta a avaliação da fisioterapia através de exercícios para reabilitação do assoalho pélvico e através de eletroestimulação no tratamento e reabilitação precoce da disfunção erétil após a prostatectomia radical.Materiais e métodos: Estudo clínico randomizado e controlado comparando três grupos: observação (G1), exercícios domiciliares do assoalho pélvico (G2) e eletroestimulação anal (G3). Os pacientes foram avaliados no pré-operatório e com 1, 3, 6 e 12 meses após a cirurgia através da perineometria (avaliar força do assoalho pélvico), eletromiografia (registro elétrico da atividade muscular) e o IIEF-5 (Índice Internacional de Função Erétil), somente o IIEF-5 foi realizado até 24 meses após a cirurgia.Resultados: Os grupos foram homogêneos quanto a presença de comorbidades, estadiamento clínico e preservação de feixes nervosos. A presença de disfunção erétil no pré-operatório foi alta (62% dos pacientes). Não houve correlação entre os tratamentos fisioterapêuticos e a recuperação da função erétil no pós-operatório. Conclusão: Não foi encontrado benefício da intervenção fisioterapêutica precoce na recuperação d... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Proposal: Prostate cancer is the most common solid tumor in men. A radical prostatectomy is important curative form of this disease, but it has one of the most feared complications that is, erectile dysfunction. Previous studies have demonstrated the action of physical therapy as a treatment for this complication, but its real importance is yet to be defined. In this paper the evaluation of physiotherapy was proposed by rehabilitation exercises for the pelvic floor and through electrostimulation in the treatment and early rehabilitation of erectile dysfunction after radical prostatectomy.Materials and methods: a randomized controlled clinical study comparing three groups: observation (G1), home pelvic floor exercises (G2) and anal electrostimulation (G3). Patients were evaluated preoperatively and at 1, 3, 6 and 12 months after surgery by perineometry (assessing strength of the pelvic floor), Electromyography (electrical record of muscle activity) and the IIEF-5 (International Index of Erectile Function). Only the IIEF-5 was performed up to 24 months after surgery .Results: The groups were homogeneous regarding the presence of comorbidities, clinical staging and preservation of nerve bundles. The presence of erectile dysfunction preoperatively was high (62% of patients). There was no correlation between the physical therapy treatments and the recovery of erectile function postoperatively. Conclusion: No benefit was found of early physiotherapy intervention in the recovery of ... (Complete abstract click electronic access below) / Doutor

Radicals are core reactive species that occur in almost every subfield of chemistry. In particular, solution phase radicals find their way into biochemistry (e.g. vitamin B12), and in polymer chemistry (e.g. radical polymerizations) just to name a few. Yet, given the proliferation of radical chemistry, there are still fundamental aspects of it that are poorly understood. This dissertation probed factors that influence the solvent cage effect. The solvent cage effect is where two radicals are held in close proximity to one another and prevented from easily escaping (to form free radicals) by a cage of solvent molecules. A convenient metric of the solvent cage effect is the radical recombination efficiency (FcP). Typically, FcP correlates with the bulk viscosity of the solution, however, this parameter only produces qualitative assessments. This dissertation outlines a method to quantitatively predict FcP using the microviscosity. This microviscosity dependence holds for non polar, aromatic, polar, and hydrogen-bonding solvents, along with solutions that contain polymers. Microviscosity is a great metric because it addresses an underlying reason for the solvent cage effect, the strength of the cage. Not only does the strength of the solvent cage around the radical pair affect FcP, but so does the identity of the radicals themselves. That is, the strength of the solvent cage is one piece to forming a total predictive model. FcP for the Cp'2Mo2(CO)6 dimer also varies with the wavelength of irradiation. Identifying the mechanism by which this wavelength dependence occurs may also provide another factor to include in an overall model of the solvent cage effect. Also, an attempt at synthesizing an asymmetric molybdenum dimer was performed. This asymmetric dimer would allow the study of solvent caged radical pairs that are different from each other. Predicting the photochemical cage pair recombination efficiency (FcP) is the major topic of this dissertation. However, there is also the collisional cage recombination efficiency (Fcʹ). This is where free radicals come together in what is called a collisional solvent cage pair. A method and values of Fcʹ are detailed later in this dissertation. This dissertation contains previously published and unpublished co-authored material.

Made available in DSpace on 2016-06-02T20:12:13Z (GMT). No. of bitstreams: 1 2374.pdf: 1948759 bytes, checksum: d042068510b4cc93c8066495ead75b48 (MD5) Previous issue date: 2009-03-06 / Universidade Federal de Minas Gerais / One of the objectives of this essay is to argue that determinism and indeterminism remain central themes of the science of psychology especially the Analysis of Behavior and its philosophy, Radical Behaviorism. At first blush, our attention seems to be misplaced, for Skinner declares himself to be a determinist. However, closer examination suggests that Skinner's writings warrant an indeterminist reading of his philosophical and scientific commitments. Accordingly, a "tension" between the determinist and indeterminist theses, underlying Skinner's writings, calls for analysis. One way of shedding light on this "tension" is to turn to philosophy. However, philosophy offers numerous definitions, as well as different levels of analysis of determinism and indeterminism. Because of this, another objective emerged: the development of an analytic tool for examining determinism and indeterminism, not only in Skinner's behaviorism, but also in philosophy. A heuristic tool was devised, based on considerations suggested by philosophy of science, which consists in three levels of analysis of determinism and indeterminism to wit, conceptual, ontological and epistemological. By means of this, some confusions and logical difficulties, often present in discussions about determinism and indeterminism, were elucidated. Some questions which arise from the examination of Skinner's work can also be addressed: Is determinism a necessary condition of science, or can there be indeterminist sciences? Are determinism and causality synonyms? Or can there be non-deterministic causation or non-causal determinism? Is determinism a condition of prediction and control? Does indeterminism imply caprice or chaos? Is probability and index of ignorance of some of the causes of behavior, or is it a constitutive element of behavior per se? Based on philosophical analyses of determinism and indeterminism, texts which broach related concepts and theses, from every decade of Skinner's intellectual production, are considered. This historical approach enables us to identify possible tendencies, regarding determinism and indeterminism, in Skinner's work. Moreover, it allows us to offer a brief history of Radical Behaviorism, interpreting its past, reconstructing its present, and indicating its future possibilities. / Um dos principais objetivos deste trabalho é argumentar que o tema do determinismo e indeterminismo é ainda central para a ciência psicológica, em especial, para a Análise do Comportamento, e sua filosofia, o Behaviorismo Radical. À primeira vista, o problema parece não se justificar, já que Skinner declara-se determinista. Todavia, um exame mais atento sugere que o texto skinneriano também abre o flanco para uma interpretação indeterminista de seus compromissos científico-filosóficos. Com isso, instala-se uma tensão entre teses deterministas e indeterministas, que reclama esclarecimento. Uma maneira de compreender essa tensão é recorrer ao texto filosófico. No entanto, há também nesse domínio uma pluralidade de definições e diferentes níveis de análise de determinismo e indeterminismo. Diante dessa situação, outro objetivo emerge: construir uma ferramenta analítica para examinar o determinismo e o indeterminismo, não só no behaviorismo skinneriano, mas também na filosofia. A partir das reflexões fomentadas pela filosofia da ciência extrai-se uma ferramenta heurística que consiste no exame do determinismo e indeterminismo privilegiando três níveis de análise: conceitual, ontológico e epistemológico. Com essa ferramenta são explicitadas eventuais confusões e embaraços lógicos que, não raro, estão presentes nas discussões do determinismo e indeterminismo. É possível também responder algumas questões que surgem no exame do texto skinneriano: determinismo é uma condição necessária para a ciência, ou haveria uma ciência indeterminista? Determinismo e causalidade são sinônimos? Ou será possível um indeterminismo causal, ou ainda, um determinismo não-causal? Controle e previsão só são possíveis no determinismo? Indeterminismo implica capricho ou caos? A probabilidade é apenas um atestado de ignorância das causas do comportamento, ou é um elemento constitutivo do próprio comportamento? A partir da matriz filosófica do determinismo e indeterminismo são examinados textos referentes a cada década da produção intelectual de Skinner, que apresentam conceitos, noções e teses diretamente relacionados ao tema principal. Essa abordagem histórica permite identificar possíveis tendências no texto skinneriano com respeito ao determinismo e indeterminismo. Não apenas isso, possibilita também construir uma breve história do Behaviorismo Radical, interpretando seu passado, reconstruindo seu presente e abrindo possibilidades para um futuro.