Dissertations / Theses on the topic 'Para-substituted'

Dans ce travail, les copolymérisations radicalaires contrôlées de monomères donneurs (dérivés du styrène) et accepteurs (maleimides N-substitués) ont été effectuées afin de préparer des polymères à séquences contrôlées. Ces macromolécules ont été préparées par polymérisation radicalaire contrôlée par la voie des nitroxides en utilisant le SG1 comme agent de contrôle. Des polymères ayant des microstructures bien définies ont été obtenus par le contrôle du temps de l’addition d’une petite quantité de monomère accepteur au cours de la polymérisation d’un large excès de monomère de type donneur. Dans cette thèse, des nouveaux dérivés styréniques para-substitués ont été sélectionnés afin de préparer une variété de polymères fonctionnels à séquences contrôlées. Par exemple, des polyélectrolytes à base de poly(4-hydroxystyrène)s et poly(vinyl benzyle amine)s ont été obtenus par polymérisation de dérivés protégés du styrène (4-tert-butoxystyrène, 4-acetoxystyrène et N-(p-vinyl benzyl)phthalimide) avec une quantité non-stœchiométrique de maleimides N-substitués. Par ailleurs, des polymères PEGylés biocompatibles et solubles dans l’eau ont également été étudiés. Des polymères à séquences contrôlées portant des fonctions alcynes protégées sur chaque unité de styrène ont été dans un premier temps synthétisés. La suppression de ces groupes protecteurs a permis le greffage du α-méthoxy-ω-azido-PEG sur les fonctions alcynes libres en employant la chimie click de type CuAAC. Finalement, des polymères semi-cristallins à séquences contrôlées ont été élaborés en utilisant le styrène d’octadécyle comme monomère donneur. Les propriétés thermiques de ces polymères ont été étudiées afin d’évaluer l’influence de la microstructure sur le comportement de leur cristallisation
In this work, controlled radical copolymerizations of donor (styrenic derivatives) and acceptor monomers (N-substituted maleimides, MIs) have been investigated in order to synthesize sequence-controlled polymers. These macromolecules were prepared by nitroxide mediated polymerization using the nitroxide SG1 as a control agent. Polymers with defined microstructures were obtained by time-controlled addition of small amounts of acceptor monomers during the polymerization of a large excess of donor monomer. In this thesis, new styrenic derivatives have been studied in order to design sequence-controlled polymers with functional backbones. For example, sequence-controlled polyelectrolytes based on poly(4-hydroxystyrene)s and poly(vinyl benzyl amine)s were obtained through the polymerization of protected styrenic derivatives (i.e. 4-tert-butoxystyrene, 4-acetoxystyrene and N-(p-vinyl benzyl)phthalimide) with non-stoichiometric quantities of N-substituted maleimides. Furthermore, the preparation of PEGylated biocompatible water-soluble polymers was also investigated. Sequence-controlled polymers bearing protected alkyne functional groups on each styrene units were first synthesized followed by the removal of their protecting groups allowing the grafting of α-methoxy-ω-azido-PEG on free alkyne moieties via CuAAC mediated click reaction. Finally, sequence-controlled semi-crystalline polymers were synthesized using octadecylstyrene as a donor monomer. The thermal properties of these polymers were studied to evaluate the influence of polymer microstructure on crystallization behavior

The project was concerned with the investigation of the electrochemical oxidation of various phenols, and to develop a viable reaction system for the production of the respective hydroquinones. Current production routes utilizing phenol as starting material have the limitations of using large amounts of acids, having to be stopped at low conversions and producing a mixture of the hydroquinones and catechols. Of the possible routes to the respective hydroquinones from the various phenols, the electrochemical oxidation of these phenols offers commercial and environmental advantages and hence formed the theme of the investigation. The synthetic possibilities proved to be more prevalent in a system when the electrochemical oxidation of these phenols was performed in an aqueous medium utilizing an organic co-solvent. Results obtained during this investigation made it possible to make certain predications about the mechanism taking place. This was found to depend on the anode material used for the oxidation. The results showed that the process developed for the electrochemical oxidation of these phenols, yields mainly the para-isomers of the respective hydroquinones and benzoquinones in good yields and selectivities, with fair current efficiencies and good mass balances at high conversions. For example: * Phenol (batch) 8 F: 345% current efficiency, 70% hydroquinone, 6% catechol, 9% benzoquinone, 9% phenol and 94 mass balance. * 2-Tert-butylphenol (flow) 10 F: 37% current efficiency, 65% hydroquinone, 33% benzoquinone, 2% phenol and 100% mass balance. * 2,6-Di-tert-butylphenol (flow) 11 F: 23% current efficiency, 92 % hydroquinone, 6% benzoquinone, 1% phenol and 99% mass balance. The developed electrochemical oxidation system offers the following advantages over previous and current methods: simplified isolation and extraction procedures, smaller amounts of acid usage, reasonably selective synthesis of the para-isomer and a less corrosive system all at high conversions.

Methcathinone (MCAT) is the β-ketone analog of methamphetamine, and like its amphetamine analog, MCAT functions as a monoamine releaser that selectively promotes the release of dopamine (DA) and norepinephrine (NE) over serotonin (5-HT). MCAT produces amphetamine-like psychostimulant effects and is classified as a Schedule I drug of abuse by the United States Drug Enforcement Administration (DEA). Recently, synthetic MCAT analogs have emerged as designer drugs of abuse in Europe and the United States and have been marketed under deceptively benign names like “bath salts” in an attempt to evade legal restriction. These dangerous, recently emergent and novel drugs of abuse display varying selectivity to promote release of DA/NE vs. 5-HT, and selectivity for DA neurotransmission is believed to correlate with abuse liability. The goal of this dissertation was to conduct preclinical research to examine structural determinants of abuse-related behavioral and neurochemical effects produced by a series of synthetic MCAT analogs. Specifically, this project focused on one feature of the methcathinone scaffold: the para substituent of the benzene ring. A series of six novel MCAT analogs will be examined to evaluate how physicochemical parameters (steric, Es; electronic, σp; lipophilic, πp) of the para substituent influence in vitro monoamine transporter selectivity as well as in vivo neurochemical and behavioral effects. Results from this body of work implicate steric factors as being particularly important in determining a compound’s abuse-related neurochemical and behavioral effects. Thus, these data not only offer an improved understanding of the mechanism of abuse-related drug effects produced by synthetic MCAT analogs, but also help in the generation of homology models of the human DA and 5-HT transporters (DAT and SERT, respectively).

This thesis describes a route towards the synthesis of alkoxy-functionalised [2.2] para-cyclophenes and [2.2]-para-cyclophane-1-enes as possible monomers for the preparation of functionalised PPVs via ROMP, using their corresponding alkoxy-functionalised stilbenes as precursors to furnish the desired cyclophenes through a ring-closing reaction. Chapter 1 is divided into three sections, A, B and C. Section A introduces the concept of conducting and electroluminescent polymers, with particular emphasis upon polyacetylene and PPV. Section B discusses stilbenes in detail, while section C examines the structure, preparation and reactivity of cyclophanes and cyclophenes, specifically [2.2] para-cyclophane and [2.2] para-cyclophene. Chapter 2 explains the synthesis of a series of alkoxy-substituted benzaldehydes, designed as easily accessible, readily functionalised precursors to alkoxy-substituted stilbenes, while Chapter 3 shows how these alkoxy-substituted benzaldehydes can be transformed into stilbenes, through the application of either the McMurry, Wittig, or Horner-Wittig reactions. Chapter 4 describes further transformations of alkoxy-substituted stilbenes, with emphasis placed upon achieving ring-closing to furnish the desired [2.2] para-cyclophenes and [2.2] para-cyclophene-1-enes. Preparation of an oligomeric form of PPV from the same stilbene precursors is also discussed, and the photophysics of both this oligomer and its related stilbenes is investigated. Chapter 5 outlines an alternative route towards alkoxy-functionalised [2.2] para-cyclophenes, via a Ramberg-Backlund rearrangement of functionalised cyclic dithioethers, and Chapter 6 gives overall conclusions for this thesis, briefly introducing possible further studies to be undertaken on this topic. Chapter 7 contains experimental details and characterisation data for all compounds prepared during the course of this work.

PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO
COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIOR
PROGRAMA DE SUPORTE À PÓS-GRADUAÇÃO DE INSTS. DE ENSINO
A Síndrome da Imunodeficiência Adquirida (SIDA/AIDS) é causada pelo HIV. De uma forma geral, o HIV é um retrovírus que ataca o sistema imunológico, principalmente os linfócitos T auxiliares (também chamados de linfócitos T4 ou T CD4+), que normalmente se encontram na corrente sanguínea e são responsáveis por toda a coordenação da defesa imunológica do organismo. Muitas estratégias de tratamento estão sendo desenvolvidas e testadas, incluindo o uso de medicamentos que impedem o vírus de entrar na célula (inibidores de fusão). Estes medicamentos representam uma abordagem muito interessante no tratamento do HIV/AIDS, uma vez que os outros tipos de fármacos atacam o vírus somente após a infecção no linfócito. Dentre os promissores candidatos a novos inibidores de fusão, destacam-se o maraviroc, vicriviroc, aplaviroc e o para-biciclo AMD 3100. Foi constatado que os biciclosexibem efeitos biológicos relevantes, toxicidade reduzida e que os substituintes ligados ao anel central interferem na atividade biológica desses compostos. Sendo assim, neste trabalho, o AMD 3100 foi considerado um protótipo para a síntese de diidrazonas, que representam uma classe de compostos orgânicos definidas pela presença do grupo funcional R1R2C=N-NR3R4. Estudos revelam que hidrazonas e várias hidrazonas substituídas estão associadas com uma ampla aplicabilidade biológica. Os espaçadores aromáticos utilizados foram os centros precursores 2,5-dimetoxitereftalaldeído, 2,5-diidroxitereftaladeído e tereftalaldeído, os quais foram modificados em posições relativas para por compostos bioativos como a hidrazida do ácido furânico, hidrazida do ácido tiofênico e hidrazida do ácido isonicotínico através de uma reação de condensação. Dessa forma, nove diidrazonas foram obtidas e caracterizadas por análise elementar, pelas técnicas espectroscópicas IV, Raman e UV-Vis, termogravimetria e RMN de 1H. Um estudo preliminar in silico (computacional) de avaliação farmacológica também foi realizado a fim de avaliar o desempenho relativo a algumas propriedades moleculares relevantes para a farmacocinética de uma droga no corpo humano. A estrutura cristalina foi obtida para apenas uma das di-hidrazonas. Baseando-se na constatação de que íons metálicos em metalofármacos contribuem para o aumento das potencialidades dos mesmos e de que os complexos de zinco com AMD3100 são os que apresentam melhores resultados biológicos, realizaram-se tentativas para obtenção de complexos de zinco para cada di-hidrazona sintetizada. Foram obtidos três complexos binucleares de zinco(II), uma vez que os demais ligantes apresentaram uma solubilidade muito baixa para se realizar as sínteses. Os complexos foram caracterizados por análise elementar, FT-IR, Raman e espectroscopia UV-Vis e termogravimetria. Concluiu-se que as di-hidrazonas relatadas nesse trabalho apresentam bons rendimentos, propriedades farmocinéticas e moleculares importantes e que a estrutura cristalina obtida apresenta duas conformações diferentes. Nos complexos, a coordenação acontece pelo sistema N2O-doador dos braços pendentes e os substituintes do anel aromático central participam da coordenação (no caso dos oxigênios dos grupos metoxila e fenol).
The Acquired Immune Deficiency Syndrome (HIV/AIDS) is caused by HIV. In general, HIV is a retrovirus that attacks the immune system, primarily helper T lymphocytes (also called T4 or CD4 + T lymphocytes) which are normally found in the bloodstream and are responsible for all the coordination of the immune defense body. Several treatment strategies are being developed and tested, including the use of drugs that prevent the virus from entering the cell (entry inhibitor). These drugs represent a very interesting approach in the treatment of HIV/AIDS, since other types of drugs attack the virus only after the infection the lymphocytes. Among the promising candidates for new fusion inhibitors, the highlights are maraviroc, vicriviroc, aplaviroc and para-bicyclo AMD 3100. It was found that the bicyclic exhibit significant biological effects, and reduced toxicity to the central ring substituents attached to interfere in the activity these organic compounds. Thus, in this work, the AMD 3100 was considered a prototype for the synthesis of di-hydrazones, which represent a class of organic compounds defined by the presence of the functional group R1R2C = N-NR3R4. Studies have shown that several hydrazones and substituted hydrazones are associated with a broad biological applicability. The aromatic spacers used were the precursors centers 2,5-dimethoxyterephthalaldehyde, 2,5-dihydroxyterephthalaldehyde and terephthalaldehyde, which were modified in relative positions to a bioactive compounds such as furan acid hydrazide, thiophenic acid hydrazide and isonicotinic acid hydrazide by a condensation reaction. Thus, nine di-hydrazones were obtained and characterized by elemental analysis, by IR spectroscopic techniques, Raman and UV-Vis spectroscopy, thermogravimetric analysis and 1H NMR. A preliminary study in silico (computational) pharmacological evaluation was also conducted to evaluate the relative performance of some relevant molecular properties for the pharmacokinetics of a drug in the human body. The crystal structure was obtained for only one of the di-hydrazone. Based on the fact that metal ions in metallodrugs contribute to increasing the potential of the same and that the zinc complexes with AMD3100 are those with best biological results, there were attempts to obtain zinc complexes for each di-hydrazone synthesized. Three complexes were obtained dinuclear zinc(II), since the other ligands showed very low solubility to carry out the synthesis. The compounds were characterized by elemental analysis, FT-IR, Raman and UV-Vis spectroscopy and thermogravimetric analysis. It was concluded that the di-hydrazone reported in this work have very good yields important farmocinéticas and molecular properties that the obtained crystal structure shows two different conformations. In the complex , the coordination takes place by the arms pending N2O - donor system and the central aromatic ring substituents involved coordination (in the case of the oxygens of methoxyl groups and phenol).

Conselho Nacional de Desenvolvimento Científico e Tecnológico
This work presents the synthesis of 41 succinimides, 24 pyrrolidinones and 8 tetrazoles, all presenting unprecedented chemical structure, except for the succinimide 3-ethoxy-1-methylpyrrolidine-2,5-dione. These compounds were synthesized by cyclization reactions of β-cyanocarboxylic acids of general formula HO2CCH(R1)CH(OR)CN, where R/R1 = Et/H (9), -(CH2)2- (10), -(CH2)3- (11), Et/Me (12), i-Pr/H (13), s-Bu/H (14), i-Pr/Me (15), s-Bu/Me (16), with amine derivatives or sodium azide. Initially NR2-substituted 3-ethoxypyrrolidine-2,5-diones were obtained from the cyclization of 3-ethoxy-3-cyanopropanoic acid 9 with a series of amine derivatives of general formula NH2R2, where R2 = -CH2-2-Py (17a), -CH2-3-Py (17b), -CH2-4-Py (17c), -CH2C6H5 (17d), -(CH2)2C6H5 (17e), -(CH2)2NMe2 (17f), -(CH2)2NEt2 (17g), Me (17h), Et (17i), Pr (17j), i-Pr (17k), allyl (17l), -(CH2)2OH (17m), -(CH2)3OH (17n), - CH2CH(OH)Me (17o), -CH(CH2OH)Et (17p), -CH(CH2OH)i-Pr (17q), -CH(CH2OH)i-Bu (17r), -CH(CH2OH)s-Bu (17s), -CH(CH2OH)Bn (17t), -CH2CO2H (17u) e - CH2CONH2 (17v). When the cyclization reaction were carried out with diamines of structure NH2(CH2)nNH2, where n = 1, 2 ou 3, the corresponding 1,1 -(alkyldiyl)bis(3- ethoxypyrrolidine-2,5-diones) were obtained. In addition, the reaction of 2-cyanotetrahydrofuran-3-carboxylic acid 10 with amines 17a-p, furnished a series of NR2- substituted 2,3,3a,6a-tetrahydrofuro[2,3-c]-5H-pyrrol-4,6-diones in good yields. In sequence, 4-ethoxy-5-hydroxypyrrolidin-2-ones and 6-hydroxy-3,3a,6,6atetrahydro- 2H-furo[2,3-c]-5H-pyrrol-4-ones were synthesized by regioselective reduction of 3-ethoxypyrrolidine-2,5-diones and 2,3,3a,6a-tetrahydrofuro[2,3-c]-5Hpyrrol- 4,6-diones, previously obtained, by reaction of acids 9 and 10 with selected nucleophiles 17a-l. The reduction reactions were performed using sodium borohydride as reducing agent and, in general, the hydroxylated products were obtained with high diastereoselectivity. Finally, [2 + 3] cycloaddition reaction between β-cyanocarboxylic acids 9-16 with sodium azide, catalyzed by zinc chloride, were carried out furnishing a series of 5-substituted 1-H tetrazoles, where R/R1 = Et/H, -(CH2)2-, -(CH2)3-, Et/Me, i-Pr/H, s- Bu/H, i-Pr/Me, s-Bu/Me.
Este trabalho apresenta a síntese de 41 succinimidas, 24 pirrolidinonas e 8 tetrazóis, todos apresentando estrutura química inédita, com exceção da succinimida 3-etóxi-1-metilpirrolidina-2,5-diona. Os compostos mensionados foram sintetizados a partir de reações de ciclização dos ácidos β-cianocarboxílicos de fórmula geral HO2CCH(R1)CH(OR)CN, onde R/R1 = Et/H (9), -(CH2)2- (10), -(CH2)3- (11), Et/Me (12), i-Pr/H (13), s-Bu/H (14), i-Pr/Me (15), s-Bu/Me (16), com derivados amínicos ou azida de sódio. Inicialmente 3-etoxipirrolidina-2,5-dionas NR2-substituídas foram obtidas a partir da ciclização do ácido 3-etóxi-3-cianopropanóico 9 com uma série de derivados amínicos de fórmula NH2R2, sendo R2 = -CH2-2-Py (17a), -CH2-3-Py (17b), -CH2-4-Py (17c), -CH2C6H5 (17d), -(CH2)2C6H5 (17e), -(CH2)2NMe2 (17f), -(CH2)2NEt2 (17g), Me (17h), Et (17i), Pr (17j), i-Pr (17k), alil (17l), -(CH2)2OH (17m), -(CH2)3OH (17n), -CH2CH(OH)Me (17o), -CH(CH2OH)Et (17p), -CH(CH2OH)i-Pr (17q), - CH(CH2OH)i-Bu (17r), -CH(CH2OH)s-Bu (17s), -CH(CH2OH)Bn (17t), -CH2CO2H (17u) e -CH2CONH2 (17v). Quando empregadas nas reações de ciclização diaminas de estrutura NH2(CH2)nNH2, onde n = 1, 2 ou 3, foram obtidas as respectivas 1,1 - (alquildiil)bis(3-etoxipirrolidina-2,5-dionas). Em adição, 2,3,3a,6a-tetraidrofuro[2,3-c]-5H-pirrol-4,6-dionas NR2-substituídas foram obtidas quando empregado o ácido 2-cianotetraidrofuran-3-óico 10 nas reações de ciclização com os derivados amínicos 17a-p. Em sequência, 4-etóxi-5-hidroxipirrolidin-2-onas e 6-hidróxi-3,3a,6,6atetraidro- 2H-furo[2,3-c]-5H-pirrol-4-onas foram sintetizadas através da redução regiosseletiva das respectivas succinimidas 3-etoxipirrolidina-2,5-dionas e 2,3,3a,6atetraidrofuro[ 2,3-c]-5H-pirrol-4,6-dionas anteriormente obtidas pela reação dos ácidos 9 ou 10 com os nucleófilos selecionados 17a-l. As reações de redução foram realizadas utilizando boroidreto de sódio como agente redutor e, em geral, os produtos hidroxilados foram obtidos com alta diastereosseletividade. Finalmente foi realizada reação de cicloadição [2+3] da série de ácidos β- cianocarboxílicos 9-16 com azida de sódio e catálise de cloreto de zinco. As reações forneceram como produtos uma série de tetrazóis 1H-5-substituídos, onde R/R1 = Et/H, -(CH2)2-, -(CH2)3-, Et/Me, i-Pr/H, s-Bu/H, i-Pr/Me, s-Bu/Me.

A presente tese trata da análise conformacional e estudo das interações eletrônicas de algumas 2-(fenilseleno)-2-(etiltio)acetofenonas (série I), 2-(fenilseleno)-2-(etilsulfinil)- acetofenonas [série IIa para (CRSR/CSSS) e série IIb para (CRSS//CSSR)] e 2-(fenilseleno)-2- (etilsulfonil)acetofenonas (série III) contendo substituintes doadores e atraentes de elétrons, além de hidrogênio na posição para do grupo fenacila. Foi constatada a ocorrência de isomerismo conformacional por espectroscopia no infravermelho em solventes de constante dielétrica crescente (n-C6H14, CCl4, CHCl3, CH2Cl2, CH3CN) em todas as séries estudadas. Os resultados obtidos por infravermelho são concordantes com as estruturas obtidas por otimização estrutural no nível de teoria B3LYP/6-31+G(d,p) com o efeito do solvente simulado pelo método PCM. As interações eletrônicas foram investigadas a partir dos contatos interatômicos e por meio da análise das interações orbitalares (NBO). Foram obtidas as estruturas cristalográficas de alguns compostos selecionados das séries IIa, IIb e III por difração de raio-X. Na série I, o confôrmero mais estável é caracterizado pelas interações orbitalares entre carbonila e enxofre, com o grupo etiltio numa geometria sinclinal em relação à carbonila, enquanto o grupo fenilselenila se aproxima da carbonila devido à repulsão eletrostática ser pequena. O efeito do solvente nas populações relativas dos confôrmeros ao longo da série I é menor que nas demais séries. As interações são significativamente modificadas com o grupo etilsulfinila (séries IIa e IIb): o átomo de enxofre é positivo, de modo que as interações orbitalares πCO→σ*CS e π*CO→σ*CS são mais intensas. Assim, em solventes de baixa polaridade, o grupo etilsulfinila mantém a preferência conformacional sinclinal em relação à carbonila na série IIa enquanto na série IIb esse confôrmero é altamente desestabilizado devido à repulsão eletrostática Oδ-(CO)...Oδ-(SO). O aumento na constante dielétrica do solvente favorece a conformação na qual o grupo etilsulfinila tende a geometria sinperiplanar em relação à carbonila, com os dipolos S=O e C=O apontando na mesma direção. Na série IIb o grupo fenilselenila adota a geometria sinclinal (que favorece as interações orbitalares) enquanto o grupo etilsulfinila tende à geometria sinperiplanar em relação à carbonila nos dois confôrmeros estáveis. A orientação do oxigênio sulfinílico em relação ao oxigênio carbonílico define a estabilidade dos confôrmeros da série IIb: enquanto solventes apolares e grupos doadores de elétrons estabilizam a conformação na qual os dipolos S=O e C=O apontam em direções opostas, solventes polares e grupos atraentes de elétrons estabilizam a conformação na qual os referidos dipolos apontam na mesma direção. Por fim, na série III (que contém o grupo etilsulfonila) a atração eletrostática cruzada entre os grupos carbonila e sulfonila é suficientemente forte para estabilizar uma mesma conformação em todos os solventes. Nessa conformação, o arranjo geométrico desfavorece as interações orbitalares entre heteroátomos e carbonila, reforçando a importância do fator eletrostático para o equilíbrio conformacional nos compostos estudados. Conclui-se que a soma das interações orbitalares envolvendo enxofre ou selênio são praticamente as mesmas para os diferentes confôrmeros de todas as séries estudadas (I-III), sendo o balanço entre as interações eletrostáticas repulsivas e atrativas o fator principal que determina a estabilidade relativa dos confôrmeros em solução.
This thesis reports the conformational analysis and the electronic interactions study of some 2-(phenylseleno)-2-(ethylthio)acetophenones (series I), 2-(phenylseleno)-2-(ethylsulfinyl)- acetophenones [series IIa (CRSR/CSSS) and series IIb (CRSS//CSSR)] and 2-(phenylseleno)-2- (ethylsulfonyl)acetophenones (series III) bearing in the para position of the phenacyl group electron donating, hydrogen and electron attracting substituents. It has been found the occurrence of conformational isomerism through infrared spectroscopy in solvents of increasing dielectric constant (n-C6H14, CCl4, CHCl3, CH2Cl2, CH3CN) in all studied series. The infrared results are consistent with the conformers obtained by structural optimization on the B3LYP/6-31+G(d,p) level of theory along with the solvent effect simulated by the PCM method. The electronic interactions were investigated from interatomic contacts and by orbital interactions analysis (NBO). Structures for selected solids of series IIa, IIb and III were obtained through X-ray diffraction analysis. In the series I, the most stable conformer is characterized by interactions between carbonyl and sulfur orbitals, with the ethylthio group bearing a synclinal geometry relative to the carbonyl group while the phenylselenyl moiety approaches the carbonyl group, due to the reduced electrostatic repulsion. The solvent effect on the relative population of the conformers through the series I is smaller than the other series. The interactions are significantly modified due the ethylsulfinyl group (series IIa and IIb): the sulfur atom is positive, leading to stronger πCO→σ*CS and π*CO→σ*CS orbital interactions. Thus, in solvents of low polarity, the ethylsulfinyl group retains the synclinal geometry relative to the carbonyl group in the serie IIa while in serie IIb this conformer is highly desistibilized due the Oδ-(CO)...Oδ-(SO) electrostatic repulsion. The increase in the dielectric constant of the solvent stabilizes the conformation in which the ethylsulfinyl group adopts a sinperiplanar geometry in relation to the carbonyl group, with the S=O and C=O dipoles pointing towards the same direction in both series. In the series IIb, the phenylselenyl group adopts the synclinal geometry (which favors the orbital interactions) while the ethylsulfinyl group tends to a sinperiplanar geometry relative to the carbonyl group in both conformers. The orientation of the sulfinyl oxygen relative to the carbonyl oxygen defines the stability of the conformers in series IIb: while nonpolar solvents and electron donating substituents stabilize the conformation in which the S=O and C=O dipoles point in opposite directions, on the other hand, polar solvents and attractive electron groups stabilize the conformation in which these dipoles point in the same direction. Finally, in the series III (which contains the ethylsulfonyl group) the crossed electrostatic attraction between the carbonyl and sulfonyl groups is strong enough to stabilize the same conformation in all solvents. In this conformation, the geometrical arrangement disfavors the orbital interactions between heteroatoms and carbonyl group, reinforcing the importance of the electrostatic factor for the conformational equilibrium in the studied compounds. It may be concluded that the sum of the orbital interactions involving sulfur or selenium atoms are practically the same for the different conformers of the studied series (I-III), being the balance of the attractive and repulsive electrostatic interactions the main factor which determine their relative stabilization in solution.

Im ersten Teil dieser Arbeit wurde die erfolgreiche Synthese einer Serie von bisTriarylamin (bisTAA) Verbindungen vorgestellt. Zum einen wurde das Substitutionmuster an der Benzol Brückeneinheit in Form einer meta- bzw. para-Ständigkeit der Redoxzentren (pX bzw. mX), und zum anderen die energetische Lage der Brückeneinheit durch zwei elektronen-schiebende oder ziehende Substituenten X (mit X = OMe, Me, Cl, CN, NO2) in 2,5-Position variiert. Im Falle der meta-Serie wurden auch einige in 4,6-Position substituierte Verbinungen hergestellt (mX46). Die neutral Verbindungen wurden bezüglich ihrer elektrochemischen und photophysikalischen Eigenschaften untersucht. Durch Oxidation konnten die gemischt valenten (MV), kationischen bisTAA-Verbindungen erzeugt werden. Der thermisch induzierte Lochtransfer (HT) wurde durch temperatur-abhängige ESR-Spektroskopie untersucht. Während die HT-Rate k und HT-Barriere ΔG in mX unbeeinflusst von den Substituenten X sind, steigen gleichzeitig k und ΔG in der pX-Serie mit zunehmenden Elektonenschub von X an. Diese zunächst widersprüchliche Beobachtung konnte durch einen ansteigenden Einfluss von Lösungsmitteleffekten und dadurch resultierend, einer zusätzlichen effektiven Barriere erklärt werden. Der optisch induzierte Lochtransfer wurde mittels UV/Vis/NIR-Spektroskopie untersucht. Die pX-Serie zeigte eine Zuhname der elektronischen Kopplung V und dementsprechende eine Abnahme von ΔG, mit Anstieg des elektonenschiebenden Charakters von X. Für mX war eine spektroskopische Bestimmung dieser Parameter nicht möglich. Die mX46-Serie zeigte ein intermediäres Verhalten, wobei MV-Verbindungen mit stark elektronenschiebenden X eine ähnliche hohe Kopplungen wie pX aufwiesen, was mit Hilfe von DFT-Rechnungen bezüglich der Molekülorbitale erklärt werden konnte. Im zweiten Teil dieser Arbeit wurde die Synthese einer Serie von Verbindungen mit Triarylamin (TAA) als Donor und Naphthalindiimid (NDI) als Akzeptor vorgestellt. Auch hier wurde zum einen das Substitutionmuster an der Benzol-Brückeneinheit in Form einer meta- bzw. para-Ständigkeit der Redoxzentren (pXNDI bzw. mXNDI) variieiet und die energetische Lage der durch X (mit X = OMe, Me, Cl, CN, NO2) in 2,5-Position variiert. Außerdem wurde die in 4,6-Position substituierte Verbinungen mOMe46NDI hergestellt. Alle Verbindungen wurden bezüglich ihrer elektochemischen und photophysikalischen Eigenschaften untersucht. Die Elektronentransferprozesse der Ladungsseparierung (CS) und Ladungsrekombination (CR) dieser Verbindungen sollten mittels transienter Absorptionsspektroskopie (TA) in Toluol untersucht werden. Für die Nitroverbindungen p-/mNO2NDI war dies nicht möglich, da sich diese unter Bestrahung zersetzten. Die CR von pXNDI waren nicht im ns-Bereich detektierbar, weshalb sich auf die mXNDI-Serie (mit X = OMe–CN) konzentriert wurde. Die CS wurde mittels fs-TA untersucht. Nach optischer Anregung konnte die Bildung eines CS-Zustandes detektiert werden, dessen Bildungsgeschwindigkeit hin zu elektronen-ziehenden Substituenten X steigt. Die CR wurde mit ns-TA untersucht. Sie findet in der Marcus invertierten Region statt und zeichnet sich wird durch ein biexponentialles Abklingverhaten, was durch ein Singulet-Triplett Gleichgewicht im CS-Zustand zustande kommt, aus. Durch Anlegen eines externen Magnetfeldes ließ sich das Abklingverhalten entscheidend verändern und es konnte eine Singulett-Triplett Aufspaltung nachgewiesen werden. Dieser Befund konnte weiterhin durch Simulation der Abklingkurven bestätigt werden. In beiden Teilen dieser Arbeit konnte ein entscheidender Einfluss der Benzolbrücke auf die auftretenden Ladungstransferprozesse gezeigt werden. Für den HT in Grundzustand der MV bisTAA Verbindungen, sowie der ET im angeregten Zustand der Donor-Akzeptor-Verbindungen, wurden die höchsten ET-Raten für die para-Serien pX und pXNDI gefunden, während die meta-Serien mX und mXNDI deutlch kleine Transferraten aufwiesen. In beiden Studien zeigten die meta46-Verbindungen mX46 und mOMeNDI46 ein intermediäres Verhalten, zwischen denen der para- und meta-Verbindungen
In the first part of this thesis, the synthesis of a series of bistriarylamine (bisTAA) compounds was presented. On the one hand, the substitution pattern of the TAA at the benzene bridging unit was varied from meta- to para-position (pX and mX), on the other hand, the energetic position of the bridging unit was tuned by use of two electron-donating or electron-accepting substituents X (with X = OMe, Me, Cl, CN, NO2) in 2,5-position. In case of the meta-series, compounds with X in 4,6-position were synthesized (mX46). The photophysical and electrochemical properties of the neutral compounds were investigated. The cationic mixed valence (MV) bisTAA compounds could be generated by oxidation. Thermally induced hole transfer (HT) in the groud state was investigated by temperature depending ESR spectroscopy. While the HT rate k and HT barrier ΔG in mX are unaffected by the substituents X, k and ΔG in the pX series increase simultaneously with increasing electron-donating strength of X. This, at first contradictory observation can be explained by an increasingly important solvent dynamic effect and an additional, effective barrier. The optically induced HT was examined by UV/Vis/NIR spectroscopy. The pX-series revealed an increase of the electronic coupling V, and correspondingly a decrease of ΔG, with an increase of the electron donating character of X. For mX, a spectroscopic determination of these parameters was not possible. mX46 showed an intermediate behavior, MV compounds with strong electron-donating X, obtained coupling of similar magnitude as pX, which could be explained by means of DFT calculations, with regard to the molecular orbitals. In the second part of this work, the synthesis of a series of dyads with triarylamine (TAA) as a donor and naphthalene diimide (NDI) as an acceptor was presented. Again, the substitution pattern of the redox centers at the benzene bridging unit was varied in the form of a meta- or para-position (pXNDI or mXNDI) and the energetic position of the bridging unit was varied by X (with X = OMe, Me, Cl, CN, NO2) attached in the 2,5-position. Additionally, compound mOMe46NDI with methoxy substitution in 4,6-position was synthesized. The photophysical and electrochemical properties of these compounds were investigated. The electron transfer (ET) processes of charge separation (CS) and charge recombination (CR) of these were investigated by means of transient absorption (TA) spectroscopy in toluene. This was not possible for the nitro-compounds p-/mNO2NDI, since they decomposed under irradiation. In addition to that, the CR of pXNDI was not detectable by ns-setup, which is why the focus was given to the mXNDI series (with X = OMe–CN).The CS was examined by fs-TA spectroscopy, where the formation of a CS state could be detected. The rise time of the CS states decreases with increasing electron-withdrawing substituents X. CR was examined with ns-TA spectroscopy and shows a biexponential decay behavior, which is caused by singlet-triplet equilibrium in the CS state. By applying an external magnetic field, the decay behavior was decisively changed and the singlet-triplet splitting could be determined. This finding could also be confirmed by simulating the decay curves. In both parts of this work, the decisive influence of the benzene bridging unit on the appearing ET processes became obvious. For the HT in the ground state of the MV compound, as well as for the ET in the exited states of the DA compounds, the highest transfer rates were found for the para-series pX and pXNDI, and much smaller rates for the meta-series mX and mXNDI. The meta46-compounds mX46 and mOMeNDI46 showed an intermediate behavior in both parts of this work

The cytochrome P450 enzyme CYP199A4 from Rhodopseudomonas palustris strain HaA2 is highly specific for the regioselective oxidation of para-substituted benzoic acids. A selection of these compounds was tested with the enzyme with the aim of investigating the mechanism of different P450-catalysed reactions. These studies revealed that the binding affinity and oxidative activity of CYP199A4 is influenced by the substituent at the para-position, and that to the enzyme’s known oxidative activities (demethylation, hydroxylation, heteroatom oxidation and desaturation) can be added alkene epoxidation, alkyne oxidation and aldehyde oxidation. The active oxidants involved in these CYP199A4-catalysed oxidations were investigated using two active site mutants at the conserved acid-alcohol pair, T252A CYP199A4 [CYP199A4 subscript] and D251N CYP199A4 [CYP199A4 subscript], which should disrupt different steps of the catalytic cycle. There was a general increase in hydrogen peroxide uncoupling in the T252A CYP199A4 [CYP199A4 subscript] mutant but significant levels of product formation were observed with each substrate. The D251N mutation reduced the activity of the enzyme dramatically in all but one case, suggesting that this mutation interferes with proton delivery as expected. The elevated rate of 4-ethynylbenzoic acid oxidation by T252A CYP199A4 [CYP199A4 subscript] when compared to the wild-type enzyme suggested the involvement of Cpd 0 in alkyne oxidation, while a reduction in activity with 4-methoxybenzoic acid implicated Cpd I in demethylation. Additionally, the notable increase in product formation and coupling efficiency of D251N CYP199A4 [CYP199A4 subscript] with 4-formylbenzoic acid suggested the involvement of the peroxo-anion in aldehyde oxidation. Larger cinnamic acids and closely related substrates were also investigated with CYP199A4. The binding affinity and oxidative activity of the enzyme decreased in the order 4-methoxybenzoic acid > 4-methoxycinnamic acid > 3-(4- methoxyphenyl)propionic acid > 4-methoxyphenylacetic acid, highlighting its selectivity for a planar, benzoic acid- or cinnamic acid-like framework. The exclusive oxidation of cinnamic acids and related derivatives at the para-position further demonstrated the high regioselectivity of CYP199A4. While CYP199A4 exhibited low oxidation activity towards para-methoxy substituted benzene derivatives, considerably higher levels of activity reminiscent of the demethylation of 4-methoxybenzoic acid were observed for the Ser244 → Asp244 (S244D) mutant of CYP199A4. The exclusive demethylation of the para-methoxy substituted benzenes by S244D revealed that the regioselectivity of CYP199A4 oxidation is maintained in this mutant. The regioselectivity of the S244D mutant was further investigated using a selection of methyl- and ethyl-substituted derivatives. The methyl analogues were exclusively oxidised at the para-position to a single α-hydroxylation product. α-Hydroxylation and Cα [α subscript] -Cᵦ desaturation products were generated in the turnovers of the ethyl derivatives. The alcohol was formed with high stereoselectivity. The electronic properties of the ethyl substrates were found to influence the ratio of hydroxylation/desaturation product, with the more electron donating substrates giving rise to a greater proportion of the latter. This suggested the involvement of a cationic intermediate in CYP199A4- catalysed desaturation.
Thesis (M.Phil.) -- University of Adelaide, School of Physical Sciences, 2016.

碩士
中國文化大學
化學系應用化學碩士班
105
Two sections are included in this thesis, and the first section will describe the preparation of p-phenylazocalix[4]arenes. Calixarenes are the cyclic oligomers of p-substituted phenols and formaldehyde condensed product. The structure of the calixarenes contains a molecular cavity, which is able to occlude small organic molecules or metal ions to from “host-guest”complex. These phenomena have been proposed in the application of ion separation and micro-analysis. It is known that the formation of the complexes may alter the absorption maximum of the phenylazo chromophore, therefore, the preparation of the p-phenylazocalix[4]arenes will be able to study the ion bonding ability between the metal ions and calixarenes. In the presence of a base, p-tert-butylphenol and formaldehyde was polymerized to form a yellowish precursor. Refluxing of this precursor in diphenyl ether afforded the p-tert-butylcalix[4]arene. The p-tert-butyl groups were removed with AlCl3 via the reverse Friedel-Crafts reaction to give the parent calix[4]arene. Literature reported that calix[4]arene was tribenzoated by treating with excess benzoyl chloride in pyridine at ice bath temperature for 2 hours. The phenol portion was oxidized with chlorine dioxide to yielded calix[4]monoquinone tribenzoate. The quinone moiety was then react with various p-substitute phenylhydrazine to give the corresponding hydrazone intermediate, which was converted to p-phenylazocalix[4]arenes upon tautomerization. The second section of the thesis is concentrated on the preparation of β-(1-6)-linked N-acetyl-D-glucosamine polysaccharide. The procedure started with acetylation of D-glucosamine to afford D-glucosamine pentacetate; and the pentacetylated product was then treated with thiophenol and tin(IV) chloride to yield C-1 thiophenyl ether derivative. The protected acetyl groups were removed by NaOCH3 in methanol. The free C-1 primary hydroxyl group was selective converted with bulky TBDPS group, and the two other secondary hydroxyl groups (C-3 and C-4) were then reprotected by acetylation to afforded Building Block A. Removal of C-6 TBDPS group from Building Block A by TBAF yielded Building Block B. The free C-6 hydroxyl group of Building Block B was able to replace the C-1 thiophenyl ether group of Building Block A to give a disaccharide product. In theory, repeating the coupling reaction between C-6 hydroxyl of Building Block B and C-1 thiophenyl ether group of Building Block A will afford the desired β-(1-6)-linked N-acetyl-D-glucosamine polysaccharide.

碩士
國立臺灣大學
化學工程學研究所
97
In recent years, polymer systems have attracted significant research interest for memory device applications due to their tunable electrical properties through molecular design and good processibility. The representative classes of polymer materials used for fabrication on memories are conjugated polymers, non-conjugated polymers (functional polyimide systems or polymers with specific pendent donor or acceptor moiety) and polymer nanocomposites (metal nanoparticle or fullerene embedded). However, the effects of polymer structure on the memory characteristics have not been fully explored yet. In this thesis, the homopolymers pendant with donors or acceptors and related copolymers containing of both donor and accepter units were synthesized and evaluated on memory devices. In chapter 2, the homopolymers with pendant para-substituted dicyano- triphenylamine (D, as donor) or three different oxadiazole derivatives (2-phenyl-5-(4-vinylphenyl)-1,3,4-oxadiazole (A1), 2-(4-vinylbiphenyl)-5-(4-phenyl)- 1,3,4-oxadiazole (A2), and 2-(4-vinylbiphenyl)-5-(4-ethoxyphenyl)-1,3,4-oxadiazole (A3), as electron acceptor) and also related random copolymers consisting of pendant donor and acceptor moieties (the ratio of donor:acceptor is 8:2, 5:5 and 2:8, respectively) were synthesized by Nitroxide-Mediated Living Free Radical Polymerization (NMP) and characterized by 1H NMR spectrum and element analysis (EA). The para-substituted dicyano groups on triphenylamine improve the stability without the dimerization. The side-chain acceptor A2 shows more conjugated length relative to A1 by introducing another benzene ring, and A3 system further enhances the electronic density by adding terminal electron donating moiety (-OEt). The two thin film absorbance peaks of copolymers at 353 nm and 308 ~ 332 nm belong to the corresponding homopolymers (PD at 355 nm, PA1 at 308 nm, PA2 at 330 nm, PA3 at 332 nm, respectively) and the relative absorbance of two peaks vary with donor and acceptor ratios. The band gaps calculated from absorption edge are in the range of 3.11 ~ 3.20 eV and increase slightly with the larger acceptor content. The HOMO and LUMO energy levels of the random copolymers with different donor and acceptor ratios obtained from cyclic voltammetry (CV) are almost the same with the corresponding HOMO level of donor (-5.63 eV) and LUMO levels of acceptor (-2.63 ~ 2.81 eV), respectively, mainly due to poor hybridization of adjacent donor and acceptor which could be considered as an isolated system. The electronic properties can be well-tuned through different donor-acceptor structures and ratios of the copolymers systems. In chapter 3, the memory device of the random copolymers and homopoymers are fabricated and measured in ambient atmosphere. Different solvents (N,N-dimethyl formamide (DMF) or chlorobenzene (CB)) are chosen for polymer thin film processing. The bistable memory behavior is conducted by a simple sandwich device configuration consisted of spin-coated polymer film between indium-tin oxide (ITO) bottom electrode and aluminum (A1) top electrode. All the polymers exhibit nonvolatile flash type of switching behavior. The memory devices have low turn-on threshold voltage below 1 V and exhibits long retention time of 11000 seconds. The mechanism of the switching behavior is based on filamentary conduction with space charge limited current (SCLC) theory. As the polymer films prepare from DMF, the OFF state current during erasing scan increases from 10-5 A to 10-2 A after several WRER cycles. These phenomena are further obviously demonstrated in the case of the larger acceptor contents of the random copolymers (5:5 and 2:8 donor:acceptor ratio) and homopolymers pendant with acceptor due to the presence of the binding heteroatom (N) on acceptor with Al which contributes to filament conductions. Introducing electron donating ethoxy substituent (A3) which enhance the binding ability of N atom of oxadiazole group makes the memories difficult to turn off and also keep them on the high conductance since the stable filament channel are formed. The memory can still restore to the initial OFF state if the erasing process scan more negatively which also means the enhanced threshold voltage (from -3 V to -5 V) as the acceptor ratio increases. The polymer surface prepared from the CB solution is smooth and the current elevation of OFF state during the erasing switch could not be found. The study demonstrates that pendent donor/acceptor structures and ratio of copolymer and processing condition on the switching characteristics of memory device are fully explored.

博士
國立臺灣大學
化學研究所
101
We use oxadiazole as the main core to construct two systems in this thesis. The first system to construct oxadiazole small molecules and polymer with side chains of oxadiazole. The second system to construct of oxadiazole with fluorene copolymer. These molecules are identified by fluorescence and cyclic voltammetry to understand the molecular conformation and its special physical properties. In additon, we synthesized two compounds. One contains oxadiazole groups, the other includes triphenylamine and fluorene. We found exciplex in two compound combination in solid phase. It does not form exciplex when phase separation in this combination and polymer matrix at room temperature. By controlling the temperature can be observed exciplex phenomena. By using fluorescence and surface analysis methods to understand the formation mechanism of exciplex.