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In this dissertation, I examine the evolution of the green chemistry movement from its inception in the early 1990s to the present day. I focus my study on the discursive strategies employed by leaders of the movement to establish green chemistry and to develop and institute changes in the practice of the chemical sciences. The study looks specifically at three different strategies. The first is the construction of a historical narrative. This history comes from the intersection of the chemical sciences with environmentalism in the United States retold to place chemistry in a central position for understanding global environmental health issues and green chemistry as the natural response to these problems. The second involves the attempts made to develop a concrete definition for green chemistry as well as a set of guiding principles for the practice of this alternative form of chemistry. The establishment of the definition and the principles, I argue, constitutes an important move in constituting the field as a very specific interdisciplinary group with a forged identity and the beginnings of a system for determining what properly "counts" as green chemistry. The third comes from the intersection of this history within the defining principles of the movement intersect to create a specific set of green chemistry practices, and how these practices manifest themselves in conference and pedagogical settings. Finally, I offer an overview of where the movement currently stands, offering a critical perspective on the future potential of the field. I argue that recent episodes indicate that the movement has not succeeded in accomplishing what it set out to do, and will continue to encounter problems unless a refashioning of the movement takes place. To offer perspective on green chemistry as a movement, I examine it through the lens of other (e.g., Frickel and Gross 2005) attempts to explore scientific movements as a special class of social movements. / Ph. D.

An environmentally friendly, operationally simple copper-amine catalyst system is disclosed. Using this catalyst system, electron deficient alkenes and alkynes with diverse functional groups are borylated and silylated in high yields and with short reaction times. In the case of electron deficient alkynes the identity of the electron withdrawing group controlled diastereoselectivity. Esters and amides exclusively form E-product, while aldehydes and ketones favor Z-product. Mechanistic insights into the catalytic cycle as well as origin of diastereoselectivity are discussed. / Master of Science

Le but de notre projet était d’établir un procédé éco-compatible pour la synthèse de composés possédant une activité antioxydante. Le choix des molécules cibles s’est porté sur des glycosylflavonols. Plutôt que d’effectuer une synthèse totale des composés existant dans la nature, difficilement isolés, et montrant une activité intéressante, nous avons choisi de préparer une nouvelle classe de molécules dont les éléments structuraux nécessaires à l’activité antioxydante sont maintenus mais présentent un lien glycosidique facile à réaliser. Chaque étape de la synthèse a été conçue et réalisée en suivant les principes de la chimie verte. Nous avons donc favorisé les réactions à l’économie d’atomes élevée, évité l’utilisation de groupements protecteurs et utilisé des solvants verts : polyéthylène glycol, eau, éthanol. La stratégie mise en place s’appuie sur une synthèse convergente. D’une part le motif sucre est synthétisé sous forme d’un C-glycoside afin d’augmenter sa stabilité par rapport à des conditions d’hydrolyse chimique ou enzymatique. D’autre part la synthèse de différentes polyhydroxychalcones par une nouvelle méthode ne nécessitant pas de groupements protecteurs a permis d’obtenir différents motifs flavonoïdes. Le lien entre le motif sucre et les motifs flavonoïdes a ensuite été établi en utilisant la réaction de cycloaddition catalysée par le cuivre (I) entre un azoture et un alcyne. Cette réaction a par ailleurs été l’objet d’une étude qui a montré que le polyéthylène glycol est un solvant de choix pour cette réaction puisqu’il permet notamment de réduire la contamination des produits de synthèse par le cuivre.Ainsi deux glycosylflavonols et quatre mélanges glycosylchalcone-glycosylflavanone ont été synthétisés en milieu éco-compatible et sans groupement protecteur. De plus, les réactions et les étapes de purification ont été optimisées afin de réduire la quantité de déchets générés au cours du procédé. Enfin, l’évaluation par les métriques de la chimie verte a été effectuée pour chaque étape de synthèse ainsi que pour la globalité du procédé. / The aim of this project was to develop an eco-friendly process for the synthesis of compounds endowed with antioxidant activity. The target molecules were glycosylflavonols. Instead of performing a total synthesis of natural compounds, difficult to isolate, and showing an interesting activity, we decided to prepare a new class of molecules in which the structural elements necessary for antioxidant activity are maintained but having a glycosidic linkage easy to achieve.Each step of the synthesis was designed and carried out following the principles of green chemistry. We have promoted reactions with a high atom economy, avoided the use of protecting groups and used polyethylene glycol, water, and ethanol as green solvents. The strategy was based on a convergent synthesis. Firstly, sugar moiety was synthesized as a C-glycoside to increase its stability with respect to conditions of chemical or enzymatic hydrolysis. On the other hand, the synthesis of different polyhydroxychalcones by a new method that does not require protecting groups yielded different flavonoid moieties. The link between the sugar moiety and flavonoids moieties was then achieved using the copper-catalyzed azide-alkyne cycloaddition (CuAAC). This reaction has also been the subject of a study that showed that polyethylene glycol is a solvent of choice for this reaction, since it allowed reducing the copper contamination of the products.Two glycosylflavonols and four mixtures of glycosylchalcone-glycosylflavanone were synthesized in eco-friendly solvents without the use of protecting groups. Furthermore, reactions and purification steps were optimized to reduce the amount of waste generated during the process. Finally, the evaluation by green chemistry metrics was performed for each step of the synthesis as well as for the whole process.

Im Rahmen der vorliegenden Dissertation wurden drei neue Zugangswege zu kettenverlängerten Kohlenhydraten aus ungeschützten Aldosen entwickelt. Dabei ermöglichen diese Protokolle die Synthese verschiedener Klassen von kettenverlängerten Strukturen. Neben der selektiven Darstellung von 2-Ketoaldonsäurederivaten konnten effiziente Zugangsstrategien zu hoch funktionalisierten bizyklischen C-Glycosiden und polyhydroxylierten Pseudopeptiden präsentiert werden. Dabei konnte gezeigt werden, dass ein breites Spektrum dieser verschiedenen Arten kettenverlängerter Kohlenhydrate aus ungeschützten natürlichen Hexose- und Pentose-Substraten zugänglich ist. Durch den Einbezug der natürlich vorhandenen Hydroxylgruppen der Aldosen ermöglichen die präsentierten Kaskadenreaktionen einen sehr effektiven Zugang zu hoch funktionalisierten Produkten, welche in Sequenzen unter Verwendung von Schützungsstrategien nur in aufwendigen, mehrstufigen Reaktionen zugänglich wären. Zudem konnte gezeigt werden, dass die natürlich vorkommende Chiralität in den verwendeten Substraten für ein stereoselektives Dirigieren der neu installierten Stereozentren nutzbar ist. Damit konnte eine bedeutende Erweiterung des bestehenden Repertoires von Methoden für die Verlängerung ungeschützter Kohlenhydrate erreicht werden.. Die entwickelten Transformationen bestechen durch ihre hohe Atomökonomie, wie auch durch ihre sehr gute ökologische und ökonomische Bilanz und erfüllen damit die Anforderungen an nachhaltige Synthesemethoden. / The scope of the presented work was the investigation of new organocatalysed synthesis strategies of carbon chain elongated carbohydrates. Here three new accesses to three different structure motifs of these biologically highly important and manifold compounds from unprotected carbohydrates were developed. Using naturally occurring, unprotected pentoses and hexoses, a wide variety of keto aldonic acids, bicyclic C-glycosides and glycosylated pseudopeptides are accessible in three different cascade reactions. All of the presented strategies enable the C-chain elongation by employment of the naturally occurring aldehyde motive without tedious protection ad deprotection protocols or synthetic modifications of the substrates. By utilisation of the chiral hydroxyl moieties of the carbohydrate chain, diastereoselective control of the installation of the stereocenters formed in the cascade reactions is achieved. The high regio- and diastereoselectivities, high yields as well as the convenient synthesis conditions of the presented protocols make the presented cascade reactions valuable tools among the already described accesses to the biological important compounds of chain elongated carbohydrates. The presented cascades enable the diastereoselective synthesis of a high variety of these motifs in only one synthetic step from readily available unprotected carbohydrates without additional modification steps. These advantages give rise to a very high atom economy of the transformations, which therefore fulfil the requirements to green chemistry and sustainable synthesis methods.

Doctor of Philosophy / Department of Chemical Engineering / Keith L. Hohn / Superparamagnetic iron oxide nanoparticle functionalization is an area of intensely active research, with applications across disciplines such as biomedical science and heterogeneous catalysis. This work demonstrates the functionalization of iron oxide nanoparticles with a quasi-monolayer of 11-sulfoundecanoic acid, 10-phosphono-1-decanesulfonic acid, and 11-aminoundecanoic acid. The carboxylic and phosphonic moieties form bonds to the iron oxide particle core, while the sulfonic acid groups face outward where they are available for catalysis. The particles were characterized by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), potentiometric titration, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), inductively coupled plasma optical emission spectrometry (ICP-OES), X-ray photoelectron spectrometry (XPS), and dynamic light scattering (DLS). The sulfonic acid functionalized particles were used to catalyze the hydrolysis of sucrose at 80˚C and starch at 130˚C, showing a higher activity per acid site than the traditional solid acid catalyst Amberlyst-15, and comparing well against results reported in the literature for sulfonic acid functionalized mesoporous silicas. In sucrose catalysis reactions, the phosphonic-sulfonic nanoparticles (PSNPs) were seen to be incompletely recovered by an external magnetic field, while the carboxylic-sulfonic nanoparticles (CSNPs) showed a trend of increasing activity over the first four recycle runs. Between the two sulfonic ligands, the phosphonates produced a more tightly packed monolayer, which corresponded to a higher sulfonic acid loading, lower agglomeration, lower recoverability through application of an external magnetic field, and higher activity per acid site for the hydrolysis of starch. Functionalizations with 11-aminoundecanoic acid resulted in some amine groups binding to the surfaces of iron oxide nanoparticles. This amine binding is commonly ignored in iron oxide nanoparticle syntheses and functionalizations for biomedical and catalytic applications, affecting understandings of surface charge and other material properties.

Triaryl phosphates were synthesized from white phosphorus and phenols in aerobic conditions and in the presence of iron catalysts and iodine. Full conversion to phosphates was achieved without the use of chlorine or chlorinated solvents, and the reactions do not produce acid waste. Triphenyl phosphate, tritolyl phosphate and tris(2,4-di-tert-butyl)phenyl phosphate were synthesized by this method with 100% conversion from P₄. Various iron(III) diketonates were used to catalyse the conversion. Mechanistic studies showed the reaction to proceed via the formation of phosphorus triiodide (PI₃), then diphenyl phosphoroiodidate (O=PI(OPh)₂) before the final formation of triphenyl phosphate (O=P(OPh)₃). The nucleophilic substitution of O=PI(OPh)₂ with phenol to form O=P(OPh)₃ was found to be the rate determining step. It was found that by modifying the reaction conditions the same catalytic systems could be used to synthesize triphenyl phosphite directly from P₄. Triphenyl phosphite was synthesized in selectivities of up to 60 %. The mechanism of these transformations was also elucidated. Independent syntheses of the intermediate in the reaction mechanism, O=P(OPh)₂I and its hydrolysis products diphenyl phosphate (O=P(OPh)₂OH) and tetraphenyl pyrophosphate ((O)P(OPh)₂-O-P(O)(OPh)₂) were developed from PI₃. The 2,4-di-tert-butyl phenol analogues of these compounds were also prepared. Bis-(2,4-di-tert-butylphenyl) phosphoroiodidate was then reacted with various alcohols to produce a series of mixed triorgano phosphates.

The bidentate ligand 1,2-bis(ditertbutylphosphinomethyl)benzene has been shown to be a very efficient catalyst for operating the alkoxycarbonylation of alkenes and unsaturated esters and carboxylic acids giving a very high selectivity to the linear product with very few exceptions to this general rule. Due to the increasing prices of petroleum feedstock and petroleum-derived chemicals, the preparation of chemicals starting from renewable resources and waste products from the industry becomes an interesting alternative. Fatty acids and fatty esters, due to the existence of one or more unsaturation in their alkyl chain are subjected to the alkoxycarbonylation reactions in presence of 1,2-bis(ditertbutylphosphinomethyl)benzene, palladium, methane sulfonic acid, carbon monoxide and methanol, yielding diesters with a long carbon chain (up to 19 carbon atoms). The diesters are shown to be readily prepared from unpurified olive, rapeseed or sunflower oils as well as from tall oil. In the last case triesters are also formed. The diesters are subjected to hydrogenation in the presence of 1,1,1-tris(diphenylphosphinomethyl)ethane, ruthenium and hydrogen, in a mixture of dioxane and water at high temperature, yielding the corresponding diols. The resulting products of the reactions are monomers for preparing polyesters having the potential to replace some existing petroleum-based polymers (for instance polyethylene). The aminocarboxylation reaction in the presence of the same palladium/1,2-bis(ditertbutylphosphinomethyl) benzene catalyst, in the presence of aniline, 2{naphthol and potassium iodide in diethylether, is employed for preparing esteramides, which are subjected to hydrogenation. Aromatic polyamides are prepared by melting together an aromatic diamine and diacids obtained from methoxycarbonylation. Finally, N-Heterocyclic Carbene (NHC) ligands are employed for preparing new palladium complexes which are used in the Suzuki-Miyaura cross-coupling reaction in a water/isopropanol mixture. Other complexes based on copper are employed for developing an inexpensive transmetallation reaction for transferring a NHC ligand from copper to palladium and gold.

M.Sc.(Nanoscience) / The synthesis and application of gold nanoparticles (AuNPs) has been intensively studied worldwide. However, the toxicity of these nanoparticles is still a concern. We considered that various physiochemical methods used to synthesize AuNPs are energy driven, costly and require the use of harmful chemicals. Thus, this makes them not environmentally-friendly. The aim of this study was therefore to synthesize AuNPs via a greener route using Aspalathus linearis tea leaves. The AuNPs were used to coat eight commercial antifungal discs (i.e. amphotericin B, fluconazole, clotrimazole, econazole, flucytosine, ketoconazole, miconazole and nystatin) against four Aspergillus spp. for enhanced antifungal activity. The aqueous extract of A. linearis was characterized by high performance liquid chromatography and liquid chromatography–mass spectroscopy. The AuNPs were characterized using ultravioletvisible (UV-vis) spectroscopy, dynamic light scattering, nanoparticle tracking analysis, Fourier transforms infrared spectroscopy (FTIR), high-resolution transmission electron microscopy and X-ray diffraction. The toxicity of the synthesized AuNPs was studied by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and xCELLigence test on HepG-2 cell lines and results revealed very little to no toxicity of the AuNPs. The pristine antifungal and AuNPs coated antifungal discs were characterized by FTIR, scanning electron microscopy (SEM) and antifungal activity performed using the disc diffusion method. A strong resonance peak was observed at 529 nm of the AuNPs measured using UV-vis spectroscopy. Average size of AuNPs was ~44±1 nm and demonstrated excellent in-vitro stability under various solutions (5% NaCl, phosphate buffered saline) at varying pH levels. The SEM images revealed that the AuNPs were attached onto the coated antifungal discs when compared with the pristine antifungal discs. Antifungal results indicated that AuNPs significantly (p<0.001) enhanced the antifungal activity of the coated antifungal discs against the tested fungi when compared to the pristine antifungal discs. The AuNPs coated econazole disc exhibited the greatest (broad spectrum) activity than other antifungal agents tested. In conclusion, A. linearis can be used as a reducing agent in the synthesis of stable AuNPs. Furthermore, the AuNPs coated antifungal discs demonstrated considerable antifungal activity over the pristine antifungal discs...

Orientador: Hérida Regina Nunes Salgado / Coorientador: Ana Carolina Kogawa / Banca: Felipe Rebelo Lourenço / Banca: Jacqueline Nakau Mendonça / Banca: Marlus Chorilli / Banca: Tais Maria Bauab / Resumo: As infecções são a segunda maior causa de mortalidade mundial e diversos são os motivos que justificam a necessidade de novos estudos de agentes antimicrobianos. A cefadroxila é um antimicrobiano β-lactâmico pertencente ao grupo das cefalosporinas de primeira geração, sendo muito prescrita para tratamentos de infecções causadas principalmente por bactérias Gram-positivas. A realização de estudos relacionados ao controle de qualidade é imprescindível aos setores industriais, pois garantem as características dos medicamentos e a segurança e saúde dos pacientes. De acordo com esta importância, o objetivo do trabalho foi desenvolver e validar métodos analíticos físico-químicos e microbiológico para a identificação e quantificação da cefadroxila monoidratada cápsulas, além de desenvolver um modelo de triagem rápido para obtenção de polimorfos da cefadroxila, o qual permitiu caracterizar as diferentes formas obtidas e compará-las com a forma comercial monoidratada, tanto em aspectos físico-químicos como solubilidade e estabilidade, quanto em atividade antimicrobiana. Os métodos desenvolvidos e validados foram espectrofotometria na região do infravermelho médio, cromatografia líquida de alta eficiência (CLAE), espectrofotometria na região do visível e ensaio microbiológico turbidimétrico, baseados na química verde e estando seus resultados em concordância com guias do ICH e legislação brasileira. No estudo de polimorfos, foram obtidas quatro diferentes formas a partir da cefadroxila... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Infections are the second largest cause of worldwide mortality and several reasons for the need of new studies of antimicrobial agents. Cefadroxil is a β-lactam antimicrobial that belongs to the first-generation cephalosporin group and is highly prescribed for treatment of infections caused mainly by Gram-positive bacteria. The studies performance is related to quality control is essential for the industrial sectors, as they will guarantee the characteristics of the medicines, the safety and health of the patients. According to this importance, the objective of the work was to develop and validate physical-chemical and microbiological analytical methods for the identification and quantification of cefadroxil monohydrate capsules, in addition to develop a rapid screening model to obtain cefadroxil polymorphs, which is allowed to characterize different forms obtained and compare them with the commercial monohydrate form, both in physical-chemical aspects as solubility and stability as in antimicrobial activity. The methods developed and validated were spectrophotometry in the medium infrared region, high performance liquid chromatography (HPLC), spectrophotometry in the visible region and turbidimetric microbiological assay. All methods based on green chemistry and their results were in agreement with ICH guides and Brazilian legislation. In the study of polymorphs, were obtained four different forms obtained from the anhydrous cefadroxil, having presented all the different for... (Complete abstract click electronic access below) / Doutor