SYNTHESIS OF MACROMOLECULAR CATALYST SYSTEMS AND APPLICATIONS Oguzkaya, Funda PhD., Department of Chemistry Supervisor: Prof. Dr. Cihangir Tanyeli September 2011, 144 pages The thesis mainly proposed to design macromolecular catalyst systems. Such catalysts should follow the way of &quot / Green Chemistry&quot / with including no metallic ions and have also the ability of reusability. Hence, nitroxide chemistry was chosen as the key point. Catalysts were synthesized with surely including TEMPO as the functional part as the most preferable nitroxide derivative. As a skeleton, norbornene was chosen firstly. Following obtaining 3-(methoxycarbonyl) bicyclo[2.2.1]hept-5-ene-2-carboxylic acid (49), 4-aminoTEMPO was attempted to be inserted in the structure. In this case, 4-aminoTEMPO was preferred as a TEMPO derivative so as to include reactive amine functional group. As a result, two different monomers were obtained. Then, Ring Opening Metathesis Polymerization via first generation Grubbs catalyst was adjusted to reach target macromolecules. Furthermore, as a second type skeleton for the catalyst, Thiophene-Pyrrole-Thiophene (SNS) structure was chosen, since these well-known structures have the ability to polymerize easily. Anelli Oxidation protocol including corresponding catalysts in combination with NaOCl+NaHCO3 (pH 9.1) and KBr resulting in remarkable high activity with low catalyst concentrations typically 1 mol % was chosen for the oxidation of alcohols so as to reach to target aldehydes and ketones. Investigation of other applicable areas via collaborative studies was thought to open the way of electrochromic and biosensor studies as the different points of view. Electropolymerization was performed in a three-electrode cell consisting of an Indium Tin Oxide coated glass slide (ITO) as the working electrode, platinum wire as the counter electrode and Ag wire as the pseudo reference electrode. As the biosensor part, glucose oxidase (GOx) was used as the model enzyme for glucose oxidation in the presence of molecular oxygen. Poly-SNS-based carboxylic acid served as an excellent immobilization matrix for glucose sensing. Key words: TEMPO, Anelli Oxidation

Chiral aromatic nitrogen heterocycles are finding many applications in asymmetric organic synthesis, particularly as ligands in the preparation of chiral metal complexes. Since camphor-based chiral auxiliaries are known to be especially effective, a number of pyridines fused to the camphor skeleton have been reported. It is well known that nicotinic acid and its derivatives exhibiting qualitatively the biological activity of nicotinamide, which acts as an electron acceptor in many biological redox reactions. In connection to our works, we attempted to develop short and convenient way to prepare various camphorderived chiral pyridine or nicotinic acid derivatives. Here we report our results obtained from the annulation of (+)-&amp / #946 / -hydroxymethylenecamphor as the feasible chiral pool with various enamines derived from active methylene compounds. (+)-&amp / #946 / -Hydroxymethylenecamphor prepared from cheap and easily available natural (+)-camphor and enamines were transformed into chiral camphor-based pyridine derivatives via tandem condensation reaction in good yields.

This study presents synthetic studies on camptothecin, a potent antitumor agent in order to improve its stability and solubility without reducing its activity. The study consists of the modification of camptothecin at 20-OH position a new strategy for the targeted and controlled release of the drug and modification at C-7 position to overcome the stability and solubility problems of the free drug. In the first part of the study, the 20-OH functional group of camptothecin was replaced with an unsymmetrical benzoin derivative that is able to release the drug under photolysis at 350 nm. The new prodrugs synthesized possessed higher stability than the camptothecin itself. The in vitro irradiation of the prodrugs at 350 nm was satisfactory without any decomposition of the active substance. The second part of the study comprises the studies on the modification of the 7th position of camptothecin, which is the most suitable position for the modification. In this part of the study, 7-amino and silyl substituted camptothecins were synthesized.Combination of camptothecin with some other drugs such as cisplatin was also investigated in this study. The synthetic efforts showed that the reactions are very promising and the combination studies can be studied as a major subject in the future.

Proefschrift--Utrecht. / "Stellingen": [2] p. inserted. Bibliography: p. 91.

Made available in DSpace on 2014-10-09T12:27:59Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:00:56Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:27:59Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:00:56Z (GMT). No. of bitstreams: 0 / O uso da energia nuclear para as mais diversas finalidades tem se intensificado e destacado pelos benefícios que proporciona. A medicina diagnóstica e terapêutica, a agricultura, a indústria, a geração de energia elétrica, são alguns exemplos. Entretanto, o uso da energia nuclear gera rejeitos radioativos e estes requerem tratamento adequado para garantir a segurança ambiental e dos seres vivos. A biossorção e bioacumulação representam uma alternativa emergente, para o tratamento de rejeitos radioativos líquidos, proporcionando redução de volume e mudança de estado físico. Este trabalho teve como objetivos estudar biossorventes para promover o tratamento de rejeitos líquidos contendo Amerício-241, proporcionando redução de volume e mudando seu estado físico para sólido. Os biossorventes avaliados foram: Saccharomyces cerevisiae imobilizadas em alginato de cálcio, Saccharomyces cerevisiae livres e inativadas, alginato de cálcio, Bacillus subtilis, Cupriavidus metallidurans e Ochrobactrum anthropi. Os resultados foram bastante satisfatórios, chegando a 100 % em alguns casos. Esta técnica parece viável para a implantação no Laboratório de Rejeitos Radioativos do IPEN - CNEN/SP a curto prazo, por ser simples e de baixo custo. / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

In the 20th-century, the advent of Taylorism led to a radical reconceptualisation in the organisation of human work. The formal scientifically-conceived aim of increased “efficiency” behind this project masked the moral and psychological changes which were also inherent in the project which is still ongoing. Now, at the turn of the 21st century, given the profusion of corporate scandals and the complicity of unscrupulous business practice in the current ecological and economic crises, researchers in a number of fields focused on work and its organisation have begun to warm to the possible relevance of religious ethics to social responsibility in business practices, offering some promise for a new rapprochement. In this dissertation, I offer a close study of the biblical texts that have nourished a moral vision of work for Christian and Jewish communities. I seek to nuance my study of these texts in Hebrew and Greek with an agrarian sensibility in order to highlight the moral vision of human / non-human interaction in the forms of work described and the ecological sensibility which undergirds this ancient vision of “good work” which is preserved in these texts. More specifically, I explore the moral relationship between work and worship through a close study of two related themes. In Part 1, I begin with a sustained look at the details of “good work” as narrated in the Tabernacle construction account in Exodus 25-40. This study of Exodus provides a platform upon which to explore work themes of volition, design, tacit knowledge, and interaction between the sociality and agency of work. In subsequent chapters, I go on to analyse subsequent temple construction accounts in 1 Kings, Jeremiah 22, Isaiah 60, Zechariah 14, 1-2 Chronicles, and across the New Testament. In this deliberately intertextual study, I attend to the transformation of the meaning of the Tabernacle/Temple across the Hebrew Scriptures and New Testament, as temple building texts in particular assume an eschatological aspect. My study of these subsequent construction accounts also adds nuance and texture to my account of moral making in conversation with several contemporary theorists, particularly with regards to work agency, aesthetics, sociality, skill and wisdom, and the material culture of work. This section culminates with the conclusion that in the New Testament, the church becomes both the product and the site of moral work building a new “temple”. Following this conclusion, in Part 2 of the dissertation, I develop a more detailed account of the relational dynamic between work and worship as it is delineated in Hebrew and Christian offertory practice. For this study, I turn to close readings of offertory practices in the Hebrew Scriptures (with special focus on Leviticus 1-3 and other Pentateuchal offertory texts), the New Testament and early Christian (1-4c.) moral philosophy. I highlight the relationship between worship and work in these liturgies and argue that in their practical logic, work is “drawn into worship.” In particular, I argue that three aspects of offertory practice may provide a framework for rehabilitating contemporary worship so that it may once again draw work into a morally formative dynamic. These three aspects correspond to the material and practised details of specific offerings and include: (1) the relativisation of utility with the burnt offering (2) the engagement of work quality and aesthetics through consecratory firstfruits offerings and (3) the sociality of liturgical work with the shared meal in the peace offering. These texts and the early Christian practices through which their liturgies were deployed hint at possible avenues for a rehabilitation of the moral work life of contemporary Christians. I argue that the proper performance of worship must “draw in” and engage the ordinary work of the people of God, and that a rehabilitation of offertory practice, particularly in light of the rich range of practices demonstrated in the Christian tradition offers a promising place for the reconceptualisation of work.

Addition reactions of nucleophilic trifluoromethyltrimethylsilane (CF3TMS) to acyl phosphonates were investigated. Various acyl phosphonates reacted readily with CF3TMS in the presence of K2CO3 to give 1-alkyl-2,2,2-trifluoro-1-trimethylsilyloxyethylphosphonate in 70-90% yields. When benzoyl phosphonates were used as starting material, after addition of CF3, the formed alcoholate undergoes phosphonatephosphate rearrangement to form the acyl anion, followed by elimination of F- to give 1-aryldifluoroethenyl phosphates in 87-97% yields. The proline&ndash / thiourea host&ndash / guest complex catalyzed intermolecular aldol reaction of aromatic aldehydes with cyclohexanone is developed. The anti-configured products were obtained in high yields and exclusively excellent nantioselectivities. The reaction is proposed to proceed according to a modified Houk&ndash / List model, in which the carboxylate moiety of the proline forms an assembly with the thiourea. These results clearly demonstrate the enormous effect of the thiourea on the reactivity and selectivity, even in an unconventional non-polar reaction medium, without the need to use low temperatures. A proline&ndash / thiourea host&ndash / guest complex is described as a good catalyst for the enantioselective nitro-Michael addition of aldehydes to nitroalkenes. The reaction is efficient with 5% of the thiourea, to give moderate to good enantioselectivity (up to 76% ee). High syn-selectivity was obtained with both branched and unbranched aliphatic aldehydes. This is the first example of self-assembly of organocatalysts with an achiral additive in a Michael addition wherein aldehydes are utilized as donors. An aldol reaction catalyzed by a proline&ndash / thiourea host&ndash / guest complex in a nonpolar solvent shows excellent nonlinear effects. This proline&ndash / thiourea system has the ability to form a hydrogen-bonding network. The enantiomeric excess of proline in a solution can be significantly enhanced by its incorporation with a urea molecule into its solid racemate. This suggests a general and facile route to homochirality, which may be involved in the origin of chirality on earth.

Design of new chiral ligands for asymmetric synthesis is important. The ligand should be economical and efficient in enantioselective transformations. For the synthesis of some natural products and biologically active compounds, optically active amines are used as important intermediates. For this reason, it is significant to develop new catalyst system which can produce optically active amines in an economical and efficient way. Our group developed PFAM ligands and used successfully for the enantioselective synthesis of organic compounds. In this work, these ligands were tested as chiral catalysts for enantioselective synthesis of amines. N-sulphonyl and N-phosphinoyl imines synthesized from aromatic aldehydes were used as the starting material for enantioselective diethylzinc addition reaction in the presence of copper salt and PFAM ligands. By improving the known procedure, N-benzylidine sulphonylaldimine was obtained in excellent yield (98%). Asymmetric diethylzinc addition reaction to N-sulphonyl and N-phosphinoyl aryaldimines provided chiral amines in up to 81% enantioselectivity and 99% yield.

Aldol addition reaction is one of the most important and most studied carbon-carbon bond forming reactions in organic chemistry. Recent studies focused on the catalytic version of this chemistry. Different from the classical Mukaiyama-type aldol reactions, chiral lewis bases have been used as promoters. In the presence of SiCl4, these reactions proceed through a cyclic transition state leading to anti aldol product as a major product with moderate-to-good diastereo and enantioselectivities. Phosphoramide derivatives, BINAPO, BINAPO derivatives, N,N-dioxides and N-oxides have been extensively used for this purpose. Recently, our group has designed new phosphine oxy aziridinyl phosphonates (POAP) as chiral Lewis bases. These promoters were used for the asymmetric aldol addition reaction between cyclohexanone and different aldehydes in the presence of SiCl4. Moreover, our previously designed phosphine oxy ferrocenyl substituted aziridinyl methanol (POFAM) ligands were also tested as Lewis bases. Among these 6 potential promoters, POAP-A gave the best results, and the aldol product were obtained in moderate to good yields up to 80%, and with moderate enantioselectivities (the highest, 66%) after standard optimization studies. Aldehyde screening experiments provided the highest enantioselectivity (68%) with 2- naphthaldehyde.