Dissertations / Theses on the topic 'Tautomerism'
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1
Loghmani-Khouzani, Hossein. "Investigations of tautomerism in 2- and 4- ketomethylquinolines." Thesis, University of Bradford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281216.
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Kazantsev, Andriy [Verfasser]. "Nucleobase tautomerism in codon-anticodon decoding / Andriy Kazantsev." Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1236695275/34.
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郭富超 and Fu-chiu Kwok. "A systematic study of heterocyclic keto-enol tautomerism and the observation of mechanistic change in the hydrolysis of someheterocyclic vinyl ethers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1987. http://hub.hku.hk/bib/B31230908.
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Kwok, Fu-chiu. "A systematic study of heterocyclic keto-enol tautomerism and the observation of mechanistic change in the hydrolysis of some heterocyclic vinyl ethers /." [Hong Kong : University of Hong Kong], 1987. http://sunzi.lib.hku.hk/hkuto/record.jsp?B1234560X.
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Lamont, R. Brian. "Studies of ring-chain tautomerism and molecular conformation by X-ray crystallography." Thesis, Queen's University Belfast, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335988.
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Moosavi, Mehr Seyed Hessam. "Novel structures and unusual reactivity powered by tautomerism and electron delocalization in salicylimines." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/62701.
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Hare, Patrick Michael. "Excited state dynamics in DNA base monomers the effects of solvent and chemical modification on ultrafast internal conversion /." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1166623261.
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McGeorge, Gary. "NMR studies of solid nitrogen-containing dyestuffs." Thesis, Durham University, 1996. http://etheses.dur.ac.uk/5197/.
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This thesis is concerned with the structural analysis of dyestuffs in their natural solid state by the application of solid-state nuclear magnetic resonance. These dysetuffs are all derived from the phenylazobenzene group, but tautomerism can produce structural changes, which have so far been uncharacterised in the solid-state for many of the dyestuffs currently under investigation. The information obtainable from (^13)C and (^15)N chemical shifts, both isotropic and anisotropic will be applied in this structure determination. Under magic-angle spinning the anisotropic nature of solid-state interactions is partially averaged or removed. The rotational resonance technique will be presented, which reintroduces the homonuclear dipolar interaction allowing dipolar coupling constants to be measured. Second-order effects arising from the (^14)N quadrupole interaction broaden spin-1/2 lines (RDC) in such a manner that bond lengths can be determined. This RDC analysis will be applied to a series of hydrazone structures to determine the (^15)N-(^14)N bond length within the hydrazone linkage. Finally, the two-dimensional magic-angle turning experiment will be discussed and applied to both the (13)C and (^15)N nuclei for a range of dyestuffs to show that accurate shielding tensor information can be obtained from large molecules.
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Moustras, Marios Zacharias. "Imine formation relating to cross-linking in cellular macromolecules." Thesis, University of Exeter, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260620.
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Shibl, Mohamed F. "Mechanisms of double proton tautomerization & quantum control of tautomerism in enantiomers by light." kostenfrei, 2006. http://www.diss.fu-berlin.de/2006/622/index.html.
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郭伯章 and Bozhang Guo. "NMR spectroscopic and kinetic studies on acyclic and homocyclic enols." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1988. http://hub.hku.hk/bib/B31231135.
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Elder, David. "Physicochemical and crystallographic investigations into the salt formation of two heterocyclic drugs." Thesis, University of Edinburgh, 1992. http://hdl.handle.net/1842/8721.
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Salt formation provides a means of altering the physicochemical and resultant biological characteristics of a drug entity without modifying its molecular structure. Many published reviews have indicated the importance of the selection of the most appropriate salt form. This work is an investigation into the salt formation of two heterocyclic drugs. This is done by the physicochemical and the crystallographic studies of 19 high resolution single crystal diffraction studies. The particular targets of the work are the selection of the most appropriate salt forms, investigations into the tautomerism and polymorphism (or pseudopolymorphism) and an understanding of the interactions most likely between these heterocyclic drugs and their specific receptor sites. Section 1 describes the effect of protonation on the absorption of drugs, the rationale for using various salt forms and the resultant effect this has on a number of physicochemical properties of the parent compound. Section 2 is a description of the experimental techniques used in the physicochemical investigations and in crystal structure determination. In Sections 3 and 7, the preparation and characterisation of the salts and modifications of the two heterocyclic drugs, GU and IM is described. In Sections 4 and 8, the physicochemical investigations into the hygroscopicity and solid-state stabilities of the salts of GU and IM is described. Van't Hoff solubility studies are used to determine the enthalpies of solution and where appropriate the relative thermodynamic stabilities of the various phases produced. The structures of 19 of the salts or modifications of GU and IM, together with their packing and hydrogen bonding interactions is described in Sections 5 and 9. Sections 6 and 10 describe the ionisation properties of these molecules. Both the guanidine and imidazole moieties of GU and IM, respectively, are tautomeric, the particular form(s) found in these investigations and the effect of protonation is discussed. The conformations of these structures are discussed and the effect of protonation, especially on the puckering of the piperazine ring, is described.
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Guo, Bozhang. "NMR spectroscopic and kinetic studies on acyclic and homocyclic enols /." [Hong Kong : University of Hong Kong], 1988. http://sunzi.lib.hku.hk/hkuto/record.jsp?B12352366.
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Peng, Chunte Sam. "Two-dimensional infrared spectroscopy of nucleic acids : application to tautomerism and DNA aptamer unfolding dynamics." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/91113.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2014.Cataloged from PDF version of thesis. Vita.
Includes bibliographical references.
The structural dynamics of nucleic acids are intimately related to their biological functions; however, our ability to study these molecular dynamics has been largely impeded by the lack of techniques that possess both high time resolution and structural sensitivity. The motivation for the work in this thesis was to develop and apply two-dimensional infrared spectroscopy (2D IR) as a new experimental tool to investigate nucleic acid dynamics. Infrared spectroscopy is sensitive to structural changes of nucleic acids and 2D IR offers sub-picosecond time resolution. 2D IR spectroscopy is advantageous over the linear infrared absorption spectroscopy because the vibrational spectrum is spread onto two frequency axes, giving rise to the structurally sensitive cross-peaks. These cross-peaks allow the determination of vibrational couplings, which encode chemical bond connectivity, distance and orientation. However, 2D IR spectroscopy of nucleic acids is underdeveloped due to the difficulties in modeling highly delocalized and coupled vibrations of nucleobases. This thesis initiated the efforts to develop 2D IR spectroscopy of nucleic acids by first characterizing the 2D IR spectra and vibrational eigenstates of nucleobases, using a model of multiple anharmonically coupled oscillators. With pronounced cross-peaks existing between all the vibrations for a give nucleobase, 2D IR spectroscopy was shown to be capable of distinguishing between different tautomers, using pyridone as a model system. Coupled with a laser-induced temperature-jump (T-jump), 2D IR was used to monitor rapidly exchanging tautomers in real time under physiological conditions on the nanosecond timescale. Systematically characterizing the tautomer exchange rates as a function of various experimental variables lead to a two-state concerted mechanism involving bridging water wires for the lactam-lactim tautomerization of 6-chloro-2-pyridone. This method was then applied to study the tautomerism of a deoxycytidine analog, KP1212, which is an anti-HIV drug. Multiple tautomers, including the normally rare enol tautomers, were found under physiological conditions. This observation supports the rare tautomer hypothesis, which states that each tautomer displays a distinct base-pairing preference, eventually leading to mutations and population collapse of the HIV viruses. Beyond studies on the single nucleotide level, 2D IR was used to characterize the structural dynamics of thrombin-binding aptamer (TBA), which is a 15mer DNA folded into a guanine-quadruplex (G-quadruplex). The 2D IR spectral signatures of G-quadruplex were established, and T-jump transient 2D IR was employed to investigate the unfolding dynamics of TBA. A mechanism of the early unfolding of TBA was proposed: A ~100 nanosecond response was attributed to the local deformation of the G-quadruplex, and a few-microsecond response was ascribed to be the fraying of the 3'-tail of TBA. This observation was consistent with a mechanism suggested by molecular dynamics simulations. Finally, the dissociation of double-stranded DNA formed by TBA and its complementary strand was found to be on the timescale of tens to hundreds of microseconds. The experiments in this thesis demonstrate the capability of 2D IR to investigate nucleic acid dynamics spanning a wide range of timescales.
by Chunte Sam Peng.
Ph. D.
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Silva, Edvonaldo Florêncio e. "Um Estudo teórico da doxorrubicina: espectroscopia no UV/Vis e reatividade." Pós-Graduação em Química, 2013. https://ri.ufs.br/handle/riufs/6100.
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The doxorubicin (DOX) assumes a prominent position among the drugs widely applied in treatment human cancer. This chemotherapeutic presents efficiency in the regression of
various neoplasms, although adverse reactions may occur. As a result several strategies have been developed to reduce the adverse effects caused by the continued use of DOX. One of these strategy is the incorporation of doxorubicin into MOF (Metal Organic Framework), since these materials can act as excellent carriers of drugs. The color change exhibited by doxorubicin as a function of pH, or even possibly when adsorbed in MOF, motivated the present work. This work consists in finding the possible factors that culminate in color change presented by DOX. This way, calculations involving the reactivity, and the UV/Vis
spectroscopy of the possible tautomeric species of doxorubicin were performed. Thus, we applied the semiempirical methods, AM1, PM3, PM6 and RM1, and also DFT. We used the method INDO/S-CIS to calculate the spectroscopic of ground state geometries of various
tautomer. All calculations revealed DOX1 as the most stable and DOX2 as the most unstable for protonated species. The method PM6 method was the more similar to the DFT by
comparing the absorption spectra of DOX1 as well as the relative stabilities of the tautomers. The relative energies between deprotonated tautomers calculated by applied methods were smaller than protonated species, because the deprotonated tautomers denote considerable
structural similarities between them. The reactivity study showed that the methods AM1 andPM3 exhibit the same qualitative behavior about the prediction of the transition state structure involved in each proton transfer reaction in the gas phase. The method PM6 resembled more
to RM1, being the only exception was the conversion DOX1 → DOX4. Each absorption spectrum calculated from the optimized geometries with the DFT method to the different
tautomeric species showed simply a band in the region of longer wavelengths (around 400 nm), which correspond to the visible region. In contrast, the absorption spectra obtained
experimentally in acidic showed three bands in the region between 400 to 650 nm, thus cannot be attributed to a single predominant tautomer system, but the simultaneous
contributing of all tautomers. The spectroscopic study of deprotonated tautomers, in order to simulate the effect of basic pH, suggests the presence also of the four tautomers deprotonated in the system, thus explaining the appearance of several absorption bands. The spectrum
obtained at pH 7 can be explained from the presence of both doxorubicin protonated as deprotonated species. Thus, the application of computational tools proved to be able to
elucidate some events associated with spectroscopy and reactivity of doxorubicin.Dentre os fármacos largamente aplicados na prática oncológica humana, a doxorrubicina (DOX) assume uma posição de destaque. Apesar de este quimioterápico apresentar eficiência na regressão de várias neoplasias, reações adversas podem surgir. Em decorrência disso várias estratégias vêm sendo desenvolvidas para reduzir os efeitos adversos provocados pelo uso contínuo da DOX. Uma dessas estratégias consiste na incorporação da doxorrubicina em MOF s (Metal Organic Framework), uma vez que estes materiais podem atuar como excelentes carreadores de fármacos. A mudança de coloração exibida pela doxorrubicina como função do pH, ou até mesmo quando possivelmente adsorvida na MOF, motivou a realização do presente trabalho, o qual consiste na busca dos possíveis fatores que culminam na mudança de coloração apresentada pela DOX. Diante isso, cálculos envolvendo a reatividade, assim como, a espectroscopia UV/Vis das possíveis espécies tautoméricas da doxorrubicina foram realizados. Para tanto, foram aplicados os métodos semiempíricos, AM1, PM3, PM6 e RM1, e também DFT. Para realização dos cálculos espectroscópicos das geometrias no estado fundamental dos diferentes tautômeros da doxorrubicina, foi utilizado o método INDO/S-CIS. Para as espécies protonadas, todos os cálculos revelaram a DOX1 como sendo a espécie tautomérica mais estável e a DOX2 como sendo a mais instável. O método PM6 foi o método que se mostrou mais similar ao DFT, comparando os espectros de absorção da DOX1, assim como as estabilidades relativas entre os tautômeros. As energias relativas entre os tautômeros desprotonados calculadas pelos diferentes métodos aplicados foram menores para os protonados, pois os tautômeros desprotonados denotam maiores similaridades estruturais entre si. O estudo de reatividade mostrou que os métodos PM3 e AM1 apresentam o mesmo comportamento qualitativo quanto à predição da estrutura do estado de transição envolvido em cada reação de transferência de próton em fase gasosa. O método PM6 assemelhou-se mais ao RM1, divergindo apenas na conversão DOX1 → DOX4. Cada espectro de absorção calculado a partir das geometrias otimizadas com o método DFT para as diferentes espécies tautoméricas apresentou simplesmente uma banda na região de comprimentos de onda maiores (por volta de 400 nm), as quais equivalem à região do visível. Diferentemente, o espectro de absorção obtido experimentalmente em meio ácido apresentou três bandas na região compreendida entre 400 nm a 650 nm, dessa forma não se pode atribuir a predominância de um único tautômero no sistema, mas sim, a contribuição simultânea de todos os tautômeros. O estudo espectroscópico dos tautômeros desprotonados visando simular o efeito do pH básico sugere a presença, também, dos quatro tautômeros desprotonados no sistema, explicando dessa forma o aparecimento das várias bandas de absorção. A atipicidade apresentada pelo espectro obtido a pH 7 pode ser explicado a partir da presença tanto de espécies de doxorrubicina protonadas como desprotonadas. Dessa forma, a aplicação das ferramentas computacionais mostrou-se capaz de elucidar alguns eventos associados a espectroscopia e a reatividade da doxorrubicina.
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Da, Chenxiao. "The Development and Applications of the HINT Scoring Function: Exploring Colchicine-Site Anticancer Agents and Tautomerism." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3002.
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The overall aim of this work was to apply HINT, an empirical scoring function based on the understanding of hydrophobicity, to analyze and predict the binding affinities and biological activities of colchicine-site anticancer agents. The second, concurrent aim was to improve the scoring function by incorporating tautomerism within the modeling process. Our belief is that proper evaluation of tautomeric forms for small molecules will improve performance of virtual screening. The novel pyrrole-based compounds targeting the colchicine site were docked into the receptor using HINT as a rescoring function. Two distinct binding modes dictated by the size and shape of a subpocket were predicted to differentiate the highly active compounds from the weak ones. Of the residues predicted to participate in binding for the active binding mode, Cys241β was revealed to form a weak but critical hydrogen bond with the ligand. A larger collection of colchicine-site agents, biologically tested in the same laboratory including our pyrrole-based compounds were subject to 3D quantitative structure-activity relationship (QSAR) study. Using results on docking the pyrrole compounds as a guide, relative binding poses and QSAR models were built to facilitate ligand design and optimization. A new 3D modeling approach was introduced to visually highlight the unique features of highly active compounds and the commonality of all compounds in the dataset using HINT maps and successfully tested on the colchicine-site agents. These results will provide valuable guidance in the future design and development of new colchicine-site agents. To incorporate tautomerism within HINT, we proposed and developed two workflow approaches: a general search tool using a simple and intuitive algorithm analyzing hydrogen shift patterns to identify and enumerate tautomeric structures, and a database that contains commonly observed tautomeric structures. The first approach was designed for small-scale docking studies and the second approach was designed for large-scale virtual screening. The tautomer module in HINT will give more accurate modeling results when the compound encountered is able to tautomerize.
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Greenwood, Jeremy R. "Pyridazinediones and amino acid receptors theoretical studies, design, synthesis and evaluation of novel analogues /." [Sydney : J. Greenwood], 1999. http://www.pharmacol.usyd.edu.au/thesis.
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Thesis (Ph. D.)--Dept. of Pharmacology, University of Sydney, 1999.Title from title screen. Interactive three dimensional molecular data and multiple colour images. Text presented in Hypertext Markup Language (.htm); images in standard formats (.jpg, .gif); molecules presented mostly as Cambridge Protein Data Bank format (.pdb); some molecules presented in alternative X. Mol cartesian co-ordinates format (.xyz); search facility in PERL script. Includes bibliographical references. A printed form was produced with limited features as a Faculty requirement; may also be issued in CD-ROM.
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Dolai, Ramapada [Verfasser], and Hans-Jörg [Akademischer Betreuer] Krüger. "Switching of Electronic States of Cobalt Dioxolene Complexes Triggered by Spin-Crossover Process and Valence Tautomerism / Ramapada Dolai ; Betreuer: Hans-Jörg Krüger." Kaiserslautern : Technische Universität Kaiserslautern, 2020. http://d-nb.info/1204425434/34.
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黃友民 and Youmin Huang. "NMR spectroscopic and kinetic studies on secondary enamines of heterocyclic oximes hydrazones and semicarbazones." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1991. http://hub.hku.hk/bib/B31232243.
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Greenwood, Jeremy R. (Jeremy Robert) 1971. "Pyridazinediones and amino acid receptors theoretical studies, design, synthesis and evaluation of novel analogues." [Sydney : J. Greenwood], 1999. http://www.pharmacol.usyd.edu.au/thesis.
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Title from title screen. Interactive three dimensional molecular data and multiple colour images. Text presented in Hypertext Markup Language (.htm); images in standard formats (.jpg, .gif); molecules presented mostly as Cambridge Protein Data Bank format (.pdb); some molecules presented in alternative X.Mol cartesian co-ordinates format (.xyz); search facility in PERL script. Includes bibliographical references. Text, numeric and representational data System requirements: for text, any standard web browser on any platform, Netscape 2.x or higher, Internet Explorer 3.x or higher; for molecular structures, viewer such as Rasmol or preferably MDL's Chemscape Chime; for search facility , an appropriately configured web server. Links to all required software for browsing on various platforms are included in the software directory in the thesis. Mode of access: World Wide Web.
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Holroyd, Leo. "Mutagenicity of 5-bromouracil : quantum chemical study." Thesis, University of St Andrews, 2015. http://hdl.handle.net/10023/7063.
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This thesis describes a computational investigation of the mutagenicity of 5-bromouracil (BrU). In Chapter 1, three models of spontaneous and BrU-induced base mispairing (rare tautomer, wobble pair, and ion) are reviewed. Chapter 2 presents the computational techniques used: electronic structure methods (Hartree–Fock-based and density functional theory) and molecular dynamics. Chapter 3 presents optimisations of the keto and enol tautomers of BrU and uracil (U) in water clusters. The enol tautomer of BrU is found to be more stable than that of U. Chapter 4 is a molecular dynamics study of the keto-enol tautomerism of BrU and U in a periodic water box. The pKₐ of BrU at N3 is found to be lower than that of U. Chapter 5 is a study of stacked base dimers containing BrU, U, or thymine (T) stacking with natural bases. Some structures were taken from the Protein Data Bank, while others were generated using an in-house methodology. BrU is found to stack more strongly than T in vacuo, but solvation and thermal effects nullify this difference. Chapter 6 discusses the significance of the results in Chapters 3–5 in terms of BrU-induced mutagenesis. Appendices A and B–D provide supplementary material to Chapters 2 and 5, respectively. Appendix E is an investigation of the “base flipping” pathway of 2-aminopurine (2AP). Both 2AP/N and A/N dinucleosides (N = thymine or guanine) are found to adopt a wide range of energy-minimum conformations – not only stacked and “flipped”, but also intermediate – and the stacked are not the most favourable by free energy. Appendix F is a list of publications and papers in preparation. One publication concerns BrU stacking. The other is a conformational study of the dipeptide tyrosine-glycine: the theoretical results are shown to be consistent with experiment (R2PI spectra) if thermal effects are taken into account.
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Schade, Alexander. "Synthese und Charakterisierung von enolisierbaren Barbituratfarbstoffen als Sensoren für Nukleinbasenderivate." Doctoral thesis, Universitätsbibliothek Chemnitz, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-qucosa-215808.
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In dieser Arbeit wird die Synthese neuartiger 5-monosubstituierter Barbituratfarbstoffe mit elektronenziehenden Substituenten in 5-Position beschrieben. Durch diese Funktionalisierung entstehen schaltbare Farbstoffe mit einer farblosen Ketoform und einer farbigen Enolform. Die Einflüsse verschieden stark elektronenziehender Substituenten sowie unterschiedlich großer konjugierter π-Systeme auf die Keto-Enol-Tautomerie wurden untersucht. Dies erfolgt einerseits mittels Röntgeneinkristallstrukturanalysen der Festkörper und andererseits mit solvatochromen Untersuchungen in Lösung. Durch die Keto-Enol-Tautomerie der Barbituratfarbstoffe wird die Wasserstoffbrücken¬bindungssequenz beim Übergang zwischen Keto- und Enol-Form verändert. Es wurde gezeigt, dass durch Zugabe von Rezeptoren mit komplementärer Wasserstoffbrückenbindungssequenz zur Enol-Form das tautomere Gleichgewicht der Barbitursäuren hin zur Enol-Form verschoben werden kann. Um hierzu verlässliche Aussagen zu erhalten wurden vergleichende Experimente mit N,N´-dialkylierten Barbituratfarbstoffen durchgeführt.
Aufgrund der Synthesestrategie der Barbituratfarbstoffe, welche ausgehend von Barbituratanionen über nukleophile aromatische Substitutionsreaktionen hergestellt wurden, war es zweckmäßig die Nukleophilieparameter der Barbituratanionen zu ermitteln. Dazu wurde der Ansatz von Mayr gewählt und die Nukleophilie von vier Barbituratanionen bestimmt.
Weiterhin konnte in dieser Arbeit die Charakterisierung von ionischen Flüssigkeiten nach der 4-Parameter-Gleichung von Catalán umgesetzt werden. Dabei gelang es erstmal für eine vielzahl verschiedener ionischer Flüssigkeiten die Polarisierbarkeit und Dipolarität getrennt voneinander mit Hilfe zweier solvatochromer Farbstoffe zu ermitteln.
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M'BOUNGOU-M'PASSI, ATHANASE. "Tautomerie enantioselective de photoenols." Reims, 1993. http://www.theses.fr/1993REIM5014.
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Au cours de ce travail, nous avons effectue l'irradiation d'un ester alpha,beta-insature a temperature variable, pour rechercher les points isocinetique et d'iso-inversion de la reaction de protonation asymetrique du photodienol. Nous avons aussi developpe une nouvelle voie de synthese asymetrique permettant d'acceder en milieu neutre a des cetones chirales. Selon cette methode, un photoenol est genere a partir d'une cetone aromatique ayant un hydrogene en gamma suivant la reaction de norrish ii. L'induction asymetrique est obtenue par tautomerie de l'enol intermediaire, en presence d'une quantite catalytique d'un inducteur chiral. L'enantioselectivite depend fortement de l'enol, du choix de l'inducteur chiral et des conditions experimentales. Pour acceder a certains inducteurs utilises au cours de ce travail, nous avons propose une methode de synthese efficace permettant d'obtenir l'aminobornanol-endo-endo enantiomoeriquement pur. Differentes methodes developpees dans la litterature ont toujours permis de l'obtenir plus ou moins contamine par ses diastereoisomeres
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Greenwood, Jeremy Robert. "Pyridazinediones and amino acid receptors: theoretical studies, design, synthesis, and evaluation of novel analogues." Thesis, The University of Sydney, 1999. http://hdl.handle.net/2123/394.
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http://www.pharmacol.usyd.edu.au/thesis This thesis is primarily concerned with a class of chemical compounds known as pyridazinediones, being 6-membered aromatic rings containing two adjacent nitrogen atoms (pyridazine), doubly substituted with oxygen. In particular, the work focuses on pyridazine-3,6-diones, derivatives of maleic hydrazide (1). Understanding of the chemistry of these compounds is extended, using theoretical and synthetic techniques. This thesis is also concerned with two very important classes of receptors which bind amino acids in the brain: firstly, the inhibitory GABA receptor, which binds g-aminobutyric acid (GABA) (2) in vivo, and for which muscimol (3) is an agonist of the GABAA subclass; secondly, Excitatory Amino Acid (EAA) receptors, which bind glutamate (4) in vivo, and in particular the AMPA subclass, for which (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) (5) is an agonist. The connection between pyridazinediones and amino acid receptors is the design, synthesis, and evaluation of structures based on pyridazinediones as potential GABA and EAA receptor ligands. Techniques of theoretical chemistry, molecular modelling, synthetic chemistry, and in vitro pharmacology are used to explore pyridazine-3,6-dione derivatives as ligands.
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Greenwood, Jeremy Robert. "Pyridazinediones and amino acid receptors: theoretical studies, design, synthesis, and evaluation of novel analogues." University of Sydney, Department of Pharmacology, 1999. http://hdl.handle.net/2123/394.
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http://www.pharmacol.usyd.edu.au/thesis This thesis is primarily concerned with a class of chemical compounds known as pyridazinediones, being 6-membered aromatic rings containing two adjacent nitrogen atoms (pyridazine), doubly substituted with oxygen. In particular, the work focuses on pyridazine-3,6-diones, derivatives of maleic hydrazide (1). Understanding of the chemistry of these compounds is extended, using theoretical and synthetic techniques. This thesis is also concerned with two very important classes of receptors which bind amino acids in the brain: firstly, the inhibitory GABA receptor, which binds g-aminobutyric acid (GABA) (2) in vivo, and for which muscimol (3) is an agonist of the GABAA subclass; secondly, Excitatory Amino Acid (EAA) receptors, which bind glutamate (4) in vivo, and in particular the AMPA subclass, for which (S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) (5) is an agonist. The connection between pyridazinediones and amino acid receptors is the design, synthesis, and evaluation of structures based on pyridazinediones as potential GABA and EAA receptor ligands. Techniques of theoretical chemistry, molecular modelling, synthetic chemistry, and in vitro pharmacology are used to explore pyridazine-3,6-dione derivatives as ligands.
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Baldasare, Corey Adam. "Quantum Chemical pKa Estimation of Carbon Acids, Saturated Alcohols, and Ketones via Quantitative Structure-Activity Relationships." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1598550823525731.
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Guven, Alaettin. "Potentially tautomeric pyridazino(4, 5-b)indolones." Thesis, University of East Anglia, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306148.
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Lannes, Anthony. "Chimie de coordination de radicaux nitronyl-nitroxyde pontants pour l’élaboration de matériaux magnétiques moléculaires : synthèse, structures cristallines, propriétés magnétiques et spectroscopie électronique." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10173/document.
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Au cours des dernières décennies, l'électronique s'est développée de manière à répondre au besoin grandissant de stocker et traiter toujours plus d'information, et elle a évolué de manière incessante vers une miniaturisation extrême. Dans ce contexte, les molécules-aimants, qui sont des entités moléculaires magnétiques, présentent une bistabilité magnétique permettant de stocker l'information dans des unités de la taille d'une molécule. Le principal frein aux applications tient aux basses températures auxquelles ces molécules présentent de telles propriétés (< 15K). Il est donc important de comprendre les mécanismes mis en jeu au sein de ces entités afin d'augmenter les températures de fonctionnement. Un moyen prometteur est de ponter deux ions de lanthanides par un ligand radicalaire. Cette approche a conduit à la conception de la molécule-aimant ayant à ce jour la plus haute température de blocage (14 K). Ce travail de thèse est dédié à la conception et à la caractérisation des structures, ainsi qu'à l'étude des propriétés magnétiques et des relations magnéto-structurales par spectroscopie électronique de molécules aimants et d'aimants à base moléculaires. Ces systèmes sont élaborés à partir d'ions de lanthanides(III) ou de manganèse(II) et de radicaux libres organiques de types nitronyl-nitroxyde. Une attention particulière sera dirigée vers la réalisation de complexes dinucléaires de lanthanides pontés par un ligand radicalaire, et sur l'étude de la brique monomérique. Nous avons exploré la possibilité d'utiliser le radical NITBzImH comme ligand radicalaire pontant des briques moléculaires de type [Ln(β- dicétone)3] et [Ln(NO3)3]. Nous nous sommes intéressés au comportement magnétique inhabituel d'un polymère de coordination de manganèse(II) pontés par les radicaux NITIm, parent de NITBzImH, puis nous avons commencé à nous intéresser à l'effet produit en remplaçant les manganèses(II) par des lanthanides(III)For the past decades, electronics have been developed in order to meet the increasing need of information storage, always evolving to the constant upgrade of their components: better, faster, smaller. Twenty-five years ago, the recently created field of molecular magnetism allowed designing entities responding to the aforementioned requirements: Single- Molecule-Magnets (SMMs). On the one hand, those are compounds showing magnetic bistability affording to stock information and on the other hand, they are the smallest entities available to design any information support. In spite of those remarkable qualities, they require very low temperature (< 15 K) to display their properties. Thus, it is of primary importance to understand underlying mechanisms in order to increase this temperature range. One promising route is to connect lanthanide dimer by a radical bridge. This method has led to the discovery of a SMM, whose blocking temperature is the highest known to date (14 K). This thesis work has been dedicated to the conception of SMMs and molecular-based magnets, as well as the characterization of their structures and magnetic properties, and their magneto-structural relationships by electronic spectroscopy. Those systems were mostly based on lanthanide(III) or manganese(II) ion and nitronyl-nitroxide organic free radicals. A special focus was made to the synthesis of dinuclear lanthanide complexes bridged by an organic free radical, and to the study of their mononuclear complex. We have studied the potential of NITBzImH radical as a bridge for [Ln(β-diketonate)3] and [Ln(NO3)3] molecular bricks. We also took interest to the unusual magnetic behavior of a manganese(II) coordination polymer, where each metal center is bridged by a NITIm radical, closely related to NITBzImH radical. Finally, we started to explore the changes induced by switching manganese(II) to lanthanide(III)
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Celik, Bayar Caglar. "Theoretical Investigation Of Tautomeric Equilibria In Certain Explosive Materials." Phd thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12615630/index.pdf.
Full textAbstract:
Explosive materials have always been attracting the attention of scientists. Various explosives either in pure bulk form or as admixtures are synthesized and investigated from different points of view. However, because of dangerous character of these materials, their syntheses and properties have to be forecasted by theoretical studies.
The new research trends of explosive materials generally include the designs of novel derivatives of well&ndashknown explosives to improve their detonation performances (heats of explosion, detonation velocities and detonation pressures) and thermal stabilities and decrease their sensitivities towards friction, electric spark, shock and impact either experimentally or theoretically. NTO (5&ndash
nitro&ndash
2,4&ndash
dihydro&ndash
3H&ndash
1,2,4&ndash
triazol&ndash
3&ndash
one) and PATO (3&ndash
picrylamino&ndash
1,2,4&ndash
triazole) are very important secondary explosives that take place in the literature for many years in terms of their explosive properties. In this thesis study, new species of these explosives have been designed to enhance their detonation performances (ballistic properties) and to lower their sensitivities and reactivities computationally. Additionally, aromatic nitration reactions and their mechanisms for unprotonated and protonated PATO species have been analyzed. The ab initio quantum chemistry methods, Hartree&ndash
Fock (HF) and Density Functional Theory (DFT), have been used in the calculations with Pople basis sets. Novel NTO and PATO tautomeric species have been designed and investigated to enlighten the effects of tautomerism on their quantum chemical properties and detonation performances in the gas phase. Various aromatic nitration mechanisms (carbon and nitrogen mono&ndash
nitration mechanisms) of unprotonated tautomeric PATO species as well as PATO have been designed in gas phase and the reaction states (pre&ndash
transition states, transition states, intermediates and nitration products) have been detected belonging to these mechanisms. Nitrations in solution phase have also been analyzed. The reaction states have been detected for carbon and nitrogen mono&ndash
nitrations of protonated PATO species in the gas phase. The detonation performances of unnitrated and nitrated PATO products have been presented.
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Walli, Adam. "Biomimetic Copper(I)-Mediated Activation of Dioxygen and Redox Non-Innocence in Copper(II) Complexes of Bis(oxazoline)s." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2014. http://hdl.handle.net/11858/00-1735-0000-0023-9636-9.
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Sevastik, Robin. "Quantum chemical moceling of enzymatic reactions : applications to the tautomerase superfamily." Licentiate thesis, KTH, School of Biotechnology (BIO), 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4702.
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In this thesis, quantum chemical methods are used to investigate enzymatic reaction mechanisms. The Density functional theory, in particular the hybrid B3LYP functional, is used to model two enzymes belonging to the tautomerase superfamily; 4-Oxalocrotonate Tautomerase (4-OT) and cis-Chloroacrylic Acid Dehalogenase (cis-CAAD). The methodology is presented and new mechanistic insights for the two enzymes are discussed.
For 4-OT, two different models are built and the potential energy curves are computed. This allows the methodology to be evaluated. The results give new insight into the energetics of the 4-OT reaction, indicating that the charge-separated intermediate is quite close in energy to the reactant species. The models also make it possible to perform in silico mutations to investigate the role of active site groups. Excellent agreement is found between the calculations and site-directed mutagenesis experiments, further substantiating the validity of the models.
For cis-CAAD, the uncatalyzed reaction is first considered and excellent agreement is found between the calculated barrier and the measured rate constant. The enzymatic reaction is then studied with a quite large active site model and a reaction mechanism is proposed.
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Sevastik, Robin. "Quantum chemical modeling of enzymatic reactions : applications to the tautomerase superfamily." Licentiate thesis, Stockholm : Bioteknologi, Biotechnology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4702.
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Henze, Rüdiger. "Tautomérisation énantiosélective d'un énol." Rouen, 1997. http://www.theses.fr/1997ROUES020.
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La réaction de l'aldéhyde 2-benzylacrylique avec des acides thiocarboxyliques donne accès à de nouveaux énols métastables. Leur conformation a été étudiée en utilisant des calculs semi-empiriques et des méthodes spectroscopiques. Des calculs AM1 ont révélé que la conformation préférée du Z-éthanethioate de 2-benzyl-3-hydroxy-2-propényle en absence de solvants fait intervenir une interaction intramoléculaire entre les groupements hydroxyle et carbonyle du thioester. Une étude par IR et par RMN a montré que la conformation du Z-1-benzènecarbothioate de 2-benzyl-3-hydroxy-2-propényle était dépendante du solvant. Dans les solvants accepteurs de liaisons hydrogène (DMSO, THF), une conformation nonplanaire a été mise en évidence. De plus, une isomérisation du Z-1-benzènecarbothioate de 2-benzyl-3-hydroxy-2-propényle, qui est le produit cinétique, en isomère E dans CDCl3 et dans le THF deutérié a été observée. Les deux formes isomères de Z-1-benzènecarbothioate de 2-benzyl-3-hydroxy-2-propényle ont montré une meilleure stabilité dans le THF que dans CDCl3. Des excès énantiomériques de 71% ont été obtenus pour la tautomérisation énantiosélective de 1-benzènecarbothioate de 2-benzyl-3-hydroxy-2-propényle. Des β-aminoalcools ont été des catalyseurs efficaces et l'influence des conditions a été étudiée avec la (-)-N-méthyléphédrine comme catalyseur. Les meilleurs résultats ont été obtenus avec la cinchonidine (71%) et la (-)-N-méthyléphédrine (57%) (isomère S). D'autres catalyseurs potentiels qui contiennent la même sousstructure 1,2 des sites fonctionnels ont été synthétisés et testés. Des amides de proline et des anilides de proline ont catalysé la tautomérisation avec des excès énantiomériques plus faibles. Des modèles d'interaction de l'énol avec les catalyseurs ont été proposés pour expliquer les résultats.
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Lecourt, Constance. "Chimie de coordination du manganèse(II) à partir de radicaux nitronyl nitroxyde et de macrocycles thiacalix[4]arènes : tautomérisme de valence et luminescence." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1173.
Full textAbstract:
La chimie de coordination de l’ion manganèse(II), à partir de radicaux nitronyl nitroxyde et de macrocycles thiacalix[4]arènes, a mis en évidence des propriétés magnétiques et optiques remarquables au sein de ses complexes. Ces matériaux moléculaires ont la particularité de manifester leurs propriétés sous l’application de stimuli externes. Ainsi, un composé lamellaire à base de polymères de coordination bidimensionnels d’ions Mn(II) et de radicaux nitronyl nitroxyde, a révélé une conversion de tautomérisme de valence induite thermiquement, et des complexes polynucléaires d’ions Mn(II)−sulfonylcalix[4]arènes ont montré une luminescence intense centrée sur l’ion métallique sous éclairement. Nos travaux de thèse s’insèrent dans la continuité de ces résultats développés antérieurement dans notre équipe. Notre objectif a été de comprendre l’origine des perturbations électroniques subies par l’ion Mn(II) dans ces complexes de coordination. Pour cela, l’étude approfondie des relations entre les structures cristallines des composés Mn(II)−radicaux et Mn(II)−thiacalix[4]arènes et leurs propriétés physiques, a été au cœur de notre recherche. Ce manuscrit présente les synthèses, les structures cristallines et la caractérisation des propriétés magnétiques et optiques de composés obtenus par des processus d’ingénierie moléculaire. La modification des ligands nitronyl nitroxyde et thiacalix[4]arènes par synthèse organique, et la substitution des contre-ions au sein de ces complexes ioniques lors de leur synthèse, ont été le fil conducteur de nos travaux. Ces modifications chimiques ont permis d’élaborer de nouveaux complexes qui présentent à leur tour une conversion de tautomérisme de valence thermo-induite ou une forte luminescence centrée sur l’ion Mn(II). La comparaison des structures et des propriétés des nouveaux complexes obtenus et antérieurs, a permis une interprétation et une rationalisation des relations structures-propriétés. Ces résultats permettront par la suite d’améliorer et de moduler, de façon maitrisée et selon la nécessité, les structures moléculaires et à l’état solide des composés suivant les propriétés viséesManganese(II) coordination chemistry, with nitronyl nitroxide radicals and thiacalix[4]arene macrocycles, revealed remarkable magnetic and optical properties. These molecular compounds show their properties under external stimuli. Recently, a lamellar compound, made of Mn(II) – nitronyl nitroxyde 2D coordination polymers, presented a thermo-induced valence tautomeric conversion, and Mn(II) – thiacalix[4]arene polynuclear complexes shown an intense luminescence centered on the metallic ion. Our PhD work takes part in the continuity of these previous results. Our goal was to understand the origin of the electronic perturbations inside these compounds. The depth study of the relationships between the structures and the physical properties was the central point of our research. This thesis will present the synthesis, the crystalline structures and the magnetic and optical characterizations of new compounds obtained by different molecular engineering processes. Organic modifications of the ligands and substitution of the counter-ion during the synthesis were the central thread of our work. Thanks to these chemical modifications, new compounds has been synthesized which are presenting also a thermo-induced valence tautomeric conversion or an intense luminescence. The comparison of all compounds made possible an interpretation and a rationalization of the structure-property relationships. Next step will be to improve or to modulate, in function of the need, the molecular or solid state structures regarding the expected properties
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Élise, Sabrina. "Synthèse et caractérisation de bis(oxazolidines) dérivées du tris(hydroxyméthyl)aminométhane pour la conception de prodrogues de répulsifs naturels." Phd thesis, Université de la Réunion, 2011. http://tel.archives-ouvertes.fr/tel-00686915.
Full textAbstract:
La réévaluation des impacts toxicologique et environnemental des répulsifs synthétiques conduit à reconsidérer les répulsifs d'origine naturelle pour la prévention des maladies transmises par les insectes (dengue, chikungunya, paludisme,...). Cette étude se rapporte aux structures de type bis(oxazolidine) envisagées comme prodrogues de répulsifs naturels par leur conversion avec le tris(hydroxyméthyl)aminométhane (TRIS). Différents protocoles et voies de synthèse ont été étudiés sur une série représentative d'aldéhydes pour définir l'étendue et les limites de l'approche permettant de concentrer deux unités d'un même principe actif au sein de bis(oxazolidines) symétriques et de reproduire un effet synergique avec deux unités différentes formant des bis(oxazolidines) dissymétriques. La fonctionnalisation des bis(oxazolidines) a été également envisagée pour moduler leur balance hydrophile-lipophile. L'étude de la réaction de cyclocondensation met en évidence l'influence des paramètres structuraux sur le procédé de synthèse des bis(oxazolidines), la stabilité des intermédiaires (monooxazolidines) et la stéréosélectivité de la réaction. L'interprétation des résultats est proposée sur la base des effets (stéréo)-électroniques. Cette étude démontre l'intérêt de cette approche chimique pour la production de prodrogues de répulsifs naturels qui peuvent constituer des atouts pour le développement durable.
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AMIEL, PASCALE. "Tautomerie et dithioalkylations du 2,5-dimercapto-1,3,4-thiadiazole : synthese de nouveaux heterocycles : 2-thione-n(3)-acridinyl-5-alkyltio-1,3,4-thiadiazoles : activites antiparasitaires et anticancereuses de quelques derives thiadiazoles." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX22955.
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Bosc, Jean-Jacques. "Etudes en série 2-amino-2-oxazolines : action d'isocyanates, synthèse, réactivité, étude physico-chimique et pharmacologique." Bordeaux 2, 1994. http://www.theses.fr/1994BOR2B001.
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Pulst, Martin [Verfasser]. "1,2,3-Triazole : Ionenleitung, Tautomerie und Defekte in Kristallen des Poly(ethylenoxid)s ; [kumulative Dissertation] / Martin Pulst." Halle, 2019. http://d-nb.info/1179184440/34.
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Gupta, Yashi. "Understanding the Role of Macrophage Migration Inhibitory Factor (MIF) and its Homologue D-Dopachrome Tautomerase (DDT) in Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1497113473427922.
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Rocha, Valéria Alves. "Síntese e estudo estrutural de azo-enaminonas." Programa de Pós-Graduação em Química da UFBA, 2006. http://www.repositorio.ufba.br/ri/handle/ri/10018.
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Valeria Rocha.pdf: 3157080 bytes, checksum: 5aeb84b9943c3f42e20393e8ad4cdcee (MD5)Made available in DSpace on 2013-04-23T14:14:08Z (GMT). No. of bitstreams: 1 Valeria Rocha.pdf: 3157080 bytes, checksum: 5aeb84b9943c3f42e20393e8ad4cdcee (MD5) Previous issue date: 2006
As azo-enaminonas pertencem a uma classe particular de enaminonas obtidas pela incorporação de um grupo azo (N=N), proveniente de sal de diazônio, ao sistema conjugado N-C=C-C=O da porção enaminona, e constituem uma nova classe de compostos orgânicos ainda pouco estudada, tanto em suas propriedades quanto em seus mecanismos reacionais, mas os poucos e recentes estudos já vislumbram suas potenciais aplicações. Entretanto, ainda há um número bastante pequeno de compostos sintetizados. Estudos preliminares indicam que esses compostos apresentam comportamento isomérico complexo, coexistindo como isômeros geométricos e apresentando tautomerismo azoenamino/hidrazoimino em uma das formas geométricas. Baseados em dados experimentais e métodos computacionais, esses compostos são candidatos, em potencial, à aplicação em óptica não linear (ONL) de segunda ordem para geração de segundo harmônico (GSH). Este fato é atribuído à extensa cadeia conjugada de elétrons p, presente na porção enaminona, intensificada pela presença do grupo azo, aliado à ação do grupo doador amino e grupos receptores (NO2, Cl) provenientes do composto azo, que incrementam o efeito push-pull de elétrons, potencializando a atividade óptica da molécula. Neste trabalho, foram sintetizadas as azo enaminonas 4-amino-3-(4-nitrofenilazo) pent-3-en-2-ona (4a), 4-amino-3-(4-clorofenilazo)pent-3-en-2-ona (4c) e as três novas azo-enaminonas 4-amino-3-(2-clorofenilazo)pent-3-en-2-ona (4b), 4-ciclo-hexilamino-3-(4-nitrofenilazo)pent-3-en-ona (4d), e a azo-enaminona 4-[1-(S-metil-etanoato de etila)-amino-3-(4-nitrofenilazo)pent-3-en-2-ona (4e), sendo que esta apresenta um carbono assimétrico em sua estrutura. Como método experimental para medida indireta da ONL desses compostos foi empregado o estudo solvatocrômico, que analisa a influência dos grupos cromóforos ao longo da estrutura molecular. Foi explorada, também, a atividade eletroquímica, isto é, o potencial redox desses compostos que se relaciona à eficiência da deslocalização intramolecular de elétrons p, como parâmetro para estimar as propriedades ópticas desses compostos. Adicionalmente, a estrutura cristalina de 4a, 4b e 4e foi identificada via difração de raios-X, sendo que a azo?enaminona 4a e 4b predomina na forma azo e 4e na forma hidrazo.
Salvador
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Schulte, Wibke Karin [Verfasser]. "D-Dopachrome tautomerase (D-DT) : functional homologue or cross-regulator of macrophage migration inhibitory factor (MIF)? / Wibke Karin Schulte." Aachen : Hochschulbibliothek der Rheinisch-Westfälischen Technischen Hochschule Aachen, 2012. http://d-nb.info/1019235020/34.
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Hofer, Luisa [Verfasser], and Stefan [Akademischer Betreuer] Endres. "Die Rolle des Macrophage-migration-inhibitory-factor-Homologs D-dopachrome tautomerase im murinen Tumormodell / Luisa Hofer. Betreuer: Stefan Endres." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1076242952/34.
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García, Ortega Héctor. "Porfirinas solubles en agua: Síntesis, homoasociación y propiedades fotofísicas de porfirinas sulfonadas 5,15-difenilsustituidas." Doctoral thesis, Universitat de Barcelona, 2003. http://hdl.handle.net/10803/2784.
Full textAbstract:
El trabajo reporta el estudio realizado sobre 5,15-difenilporfirinas sulfonadas. La sulfonación de la 5,15-difenilporfirina (DPP) con H2SO4 conc. procedió sobre la posición C2 del anillo de porfirina y en las posiciones para de los anillos fenílicos obteniéndose las porfirinas 2-sulfonato-5,15-bis(4-sulfonatofenil)porfirina (DPPS3), 5,15-bis(4-sulfonatofenil)porfirina (DPPS2A), 5-fenil-2-sulfonato-15-(4-sulfonato-fenil)porfirina (DPPS2B), 15-fenil-5-(4-sulfonatofenil)porfirina (DPPS1A) y
2-sulfonato-5,15-difenilporfirina (DPPS1B). Al utilizar H2SO4 fumante (30% SO3) la sulfonación de la DPP procedió sobre las posiciones meso libres del anillo de porfirina y para-fenílicas obteniéndose la 5,15-disulfonato-10,20-bis(4-sulfonatofenil)porfirina (DPPS4). La bromación con NBS en DMF de DPPS3 y 2-sulfonato-5,15-bis(4-sulfonatofenil)porfirina de zinc (II) (ZnDPPS3) resultó en la obtención de las porfirinas 10-bromo-2-sulfonato-5,15-bis(4-sulfonatofenil)porfirina (BrDPPS3) y 10-bromo-2-sulfonato-5,15-bis(4-sulfonatofenil)porfirina de zinc (II) (ZnBrDPPS3) respectivamente. Con los experimentos de RMN1H, 13C, NOESY1H1H, COSY1H1H, HMBC y HSQC1H13C y 1H15N se determinó que el equilibrio tautomérico a temperatura ambiente en las porfirinas DPPS3 y BrDPPS3 se encuentra desplazado hacia el tautómero trans H-N22/H-N24, concluyendo que la posición meso en las 5,15-diarilporfirinas tiene mayor influencia sobre el comportamiento cinético del tautomerismo H-N que la sustitución en la posición beta(C2). El estudio de la homoasociación de estas porfirinas demostró que a mayor grado de sustitución hay menor grado de agregación tanto en medio neutro como en medio ácido. Las porfirinas DPPS3, BrDPPS3, DPPS2A, DPPS2B, ZnDPPS3, ZnBrDPPS3, H2DPPS3, H2BrDPPS3 forman agregados tipo H. Las porfirinas H2DPPS2A y H2DPPS2B forman agregados de tipo J de geometría múltiple. La sustitución en las posiciones meso con grupos sulfonato evita la agregación de DPPS4 y H2DPPS4. El estudio por fotólisis de destello láser de los porfirinoides solubles en D2O estudiados nos indicó que a concentraciones diluidas y en ausencia de oxígeno se genera un estado triplete que se desactiva al estado fundamental por un solo camino pero que en disoluciones en las cuales hay presencia de agregados el estado triplete se desactiva por dos caminos según el modelo siguiente S0←T1→T'1→S0. En presencia de O2 los estados transitorios tanto de disoluciones diluidas como concentradas (1,0·10-7 M a 1,0·10-3 M) de los porfirinoides estudiados siguen sólo un camino de desactivación. En la mayoría de los casos estudiados, el aumento de la concentración en disoluciones genera una disminución del rendimiento cuántico de la especie transitoria pero a partir de concentraciones en las cuales hay presencia de agregados el rendimiento cuántico de la especie transitoria aumenta, en los casos de TPPS4 y la ZnTPPS4 el aumento de la concentración siempre resulta en un aumento en la formación del transitorio. De los porfirinoides estudiados los que dan mejores rendimientos cuánticos de producción de oxígeno singlete son las porfirinas base libre (TPPS4 > DPPS3 > BrDPPS3 > ZnDPPS3 > MgClo > ZnTPPS4 > ZnFTS4 > CuFTS4). En el caso de TPPS4, BrDPPS3, ZnBrDPPS3 y ZnTPPS4, el rendimiento cuántico de O2(1-delta-g) aumenta para disoluciones concentradas (aprox. 1,0·10-4 M).
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Wessner, Rachael Ann. "Theoretical Estimation of pKa’s of Pyrimidines and Related Heterocycles." Wright State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1469798346.
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Dobosz, Robert. "Badanie równowag tautomerycznych w roztworach dikarbonylowych pochodnych 2-metylopirydyny i jej benzologów." Rozprawa doktorska, [Nakł.aut.], 2007. http://dlibra.utp.edu.pl/Content/128.
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W pracy przebadano pod kątem tautomerii 24 związki (w tym 15 nieopisanych wcześniej w literaturze). Były to p-diketony o różnej budowie (alicykliczne, pierścieniowe - pięcio-, sześcio-, siedmioczłonowe) podstawione w pozycji 2 pierścieniem heterocyklicznym (pirydyl-2-yl, chinolin-2-yl)
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CASTELLI, SILVIA. "Catterizzazione della dna topoisomerasi I umana e della sua interazione con il farmaco antitumorale camptotecina." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2005. http://hdl.handle.net/2108/202651.
Full textAbstract:
La topoisomerasi I eucariotica è un enzima monomerico, il quale catalizza il rilassamento del DNA durante importanti processi cellulari, che comprendono la replicazione, la trascrizione, la ricombinazione e la condensazione cromosomica. La topoisomerasi I umana è composta di 765 amminoacidi e la struttura cristallografica della proteina priva del dominio N-terminale, insieme ad esperimenti di proteolisi hanno mostrato che la proteina è composta di quattro differenti domini: il dominio N-terminale (residui 1-214), il dominio core (residui 215635), il dominio linker (residui 636-712) e il dominio C-terminale (residui 713-765), che contiene la tirosina catalitica in posizione 723. Il ciclo catalitico della topoisomerasi I può essere diviso in una serie di passaggi, che comprendono il legame non covalente al DNA, il taglio di un singolo filamento, con la formazione di un legame covalente 3’fosfotirosinico e un’estremità 5’ libera, la rotazione controllata del filamento scissile di DNA, la risaldatura del filamento e il rilascio del substrato. La topoisomerasi I è il solo bersaglio cellulare di farmaci antitumorali della famiglia delle camptotecine, usati in molti tipi di tumori, quali il tumore ovarico e colorettale. La camptotecina ed i suoi derivati legano il complesso covalente DNA-enzima rallentando la fase di risaldatura del filamento e incrementando il tempo di vita del complesso stesso. Numerosi studi hanno suggerito che durante la fase S del ciclo cellulare la collisione delle forche replicative con i complessi covalenti stabilizzati dal farmaco, producono: rotture della doppia elica del DNA, un’inibizione della sintesi di DNA, arresto del ciclo cellulare in G2 e morte cellulare. Un comportamento simile alle camptotecine è stato proposto per il mutante Thr718Ala, della topoisomerasi I umana. Questo mutante quando espresso in lievito Saccaromyces cerevisiae determina una drammatica riduzione della vitalità cellulare, aumentando la stabilità del complesso covalente, con un meccanismo simile all’azione delle CPT. La caratterizzazione biochimica di questo mutante è stata descritta in questa tesi ed i risultati riportati dimostrano che, a 150 mM KCl, il mutante Thr718Ala ha una velocità di rilassamento del DNA più bassa dell’enzima selvatico. Gli esperimenti di rilassamento dimostrano che la diminuita efficienza del mutante, rispetto l’enzima selvatico, è indipendente dal rapporto DNA/enzima. Questo risultato esclude che la differenza di rilassamento del DNA tra le due proteine possa dipendere dalle velocità dissociazione/dissociazione. A forza ionica fisiologica l’enzima mutato e il selvatico hanno un identico equilibrio, come anche un’identica velocità di taglio e risaldatura del filamento. Questo implica che il principale effetto della singola mutazione Thr718Ala è associata con lo “step” di rotazione del filamento. Simulazioni di dinamica molecolare hanno confermato questo risultato, mostrando come la mutazione di un residuo prossimo al sito attivo può influenzare lo step catalitico di rotazione del filamento. L’analisi delle fluttuazioni quadratiche medie dei residui indica che, in prossimità del sito di mutazione, i due enzimi hanno identiche fluttuazioni e che le loro principali differenze sono localizzate nel dominio linker e nel subdominio II del core, coinvolti nella rotazione del filamento del DNA. L’equilibrio delle diverse forme del farmaco antitumorale topotecano in soluzione è stato studiato a pH moderatamente acido e fisiologico attraverso un approccio integrato sperimentale e quanto-meccanico. Lo spettro del topotecano nella regione dell’UV-visibile a pH moderatamente acido è accuratamente riprodotto solo dalle computazioni TD-DFT, che includono gli effetti del solvente. La comparazione delle bande spettrali sperimentali e calcolate, dello spettro UV-visibile a pH fisiologico, indica la presenza di un equilibrio tra le diverse forme, guidato dal microambiente del farmaco. La comparazione dello spettro di assorbimento sperimentale e calcolato ci ha permesso di identificare caratteri spettroscopici inequivocabili per le diverse forme del topotecano. E’ stato inoltre descritto il lavoro preliminare eseguito per determinare le condizioni di espressione dell’enzima di 70KDa, in cellule d’insetto e le condizioni di espressione e purificazione dei domini N e Cterminale della proteina nel sistema batterico.Eukaryotic topoisomerase I is a monomeric enzyme that catalyze the relaxation of supercoiled DNA during important processes including DNA replication, transcription, recombination and chromosome condensation. Human topoisomerase I is composed of 765 aminoacids and the crystal structure of the Nterminal truncated protein together with proteolytic experiments have shown that the enzyme is composed of four different domains: N-terminal domain (residues 1-214), core domain (residues 215-635), linker domain (residues 636-712) and C-terminal domain (residues 713-765), which includes the catalytic tyrosine 723. The catalytic cycle of the topoisomerase I may be divided into a series of steps involving: non-covalent binding to DNA, cleavage of the single strand with generation of a covalent 3’phosphotyrosyl bond and a free 5’-hydroxil, controlled rotation of the DNA scissile strand, religation and DNA release. During these steps the enzyme goes through large conformational variations without any need for energy cofactors, from an “open” structure that allows the DNA binding, to the “close” conformations observed by X-ray diffraction in which the enzyme completely ambraces the DNA. Topoisomerase I is the sole molecular target for the camptothecin class of anticancer drugs, which are used in the treatment of many types of cancers including colorectal and ovarian cancer. Camptothecin and its derivatives bind to the transient covalent topoisomerase I–DNA complex in a way that slows the religation step and therefore increases the lifetime of the covalent complex. Numerous studies suggest that during S phase, the collision of the advancing replication forks with these drug-stabilized cleavable complexes produced double-stranded DNA breaks, an inhibition of DNA synthesis, cell cycle arrest in G2 and cell death. A CPT-like behaviour was proposed for the threonine 718 to alanine mutant. This mutant when expressed in Saccaromyces cerevisiae exhibits a dramatic reduction in cell viability, enhancing the stability of the cleavable complex, with a mechanism similar to the actions of CPT. The biochemical characterization of this mutant has been described in this thesis and the results presented show that at 150 mM KCl the Thr718Ala mutant has a DNA relaxation rate lower than the wild-type enzyme. The relaxation experiment shows that the decreased relaxation efficiency of the mutant, when compared to the wild-type, is independent of the DNA/enzyme ratio. This result excludes that the difference in DNA relaxation between the two proteins can be ascribed to the enzyme association/dissociation rate. At physiological ionic strength the wild-type and mutated enzyme have an identical equilibrium, as well as an identical religation rate indicating that at this ionic strength the reduced relaxation rate of the Thr718Ala mutant is not due to a variation of the cleavage or religation rate. This imply that the main effect of the single Thr718Ala mutation is associated to the rotation step of the catalysis. MD simulation has confirmed this result showing how the mutation of a residue, Thr718, which is relatively close to the catalytic site, can influence the strand rotation step of the catalysis. The plot of the RMSF in fact indicates that in proximity of the mutation site the two enzymes have identical fluctuations and that the main differences are localized in the linker domain and in core subdomain II that are supposed to be involved in the DNA strand rotation. The equilibria between the different forms of the topotecan anticancer drug have been studied at moderately acidic and physiological pH by an integrated quantum-mechanical and experimental (UV-vis) approach. The ultraviolet –visible topotecan spectrum, recorded at moderately acidic pH, is accurately reproduced only by TD-DFT computations including solvent effects. Comparison of the experimental and calculated bands of the UV-vis spectrum at physiological pH indicates the presence of the equilibrium among different forms that is tuned by the microenvironment embedding the drug. Comparison of the computed and experimental absorption spectrum allows us to identify unequivocal spectroscopic signatures for the different topotecan forms. Moreover the preliminary work on the expression conditions for the 70KDa enzyme (Topo-70) in insect cells, and the expression and purification conditions of N and C-terminal domains of the protein in bacterial system has been described. Problems found during the experimental set-up and relative solutions are discussed.
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Elacqua, Elizabeth. "Supramolecular chemistry of molecular concepts: tautomers, chirality, protecting groups, trisubstituted olefins, cyclophanes, and their impact on the organic solid state." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/3447.
Full textAbstract:
The research presented in this thesis is founded upon the ability to mimic Nature by using highly directional forces to influence self-assembly, while achieving the formation of desired supramolecular structures. The successful engineering of such solids relies upon a full comprehension of supramolecular synthons, so as to apply them to design complex architectures. We have studied synthon formation in multifunctional pharmaceutical solids. Through the formation of salts and co-crystals, we uncovered a role of tautomers in the salt – co-crystal continuum. From a solid-state perspective, one can envisage that tautomers could promote co-crystal formation since an inherent flexibility to interconvert can accommodate geometries of different co-formers, as well as increase the number of synthons able to support a multicomponent solid. We have also employed co-crystallization to ibuprofen as a means to exploit solid-state properties. We have shown that co-crystallization with bipyridines can result in the formation of both co-crystal solid solutions and co-crystal conglomerates.
Supramolecular chemistry can also be utilized to construct target organic and metal-organic frameworks. Solid-state synthesis has emerged as a means to achieve the formation of molecular targets that are usually inaccessible via solution phase synthesis through the exploitation of molecular recognition and self-assembly. In particular, utilizing a combinatorial template strategy can facilitate a [2+2] photodimerization in the solid state. Although the template-directed strategy has helped circumvent problems associated with crystal packing, the solid state is still not routinely used for synthesis, owing, in part, to a lack of expansion to multifunctional olefins and molecular targets.
We have introduced a method to direct the reactivity of multifunctional olefins that contain two robust hydrogen bonding elements to produce heteropolytopic molecules that are of interest for the formation of metal-organic frameworks. Specifically, we developed a protecting group strategy that affords a supramolecular regiochemistry to attain the desired self-assembly. We have also extended our template approach to more conformationally-complex molecules to gain a further understanding of the rules regarding reactivity in highly substituted systems.
The end of this thesis is focused upon the solid-state synthesis of a series of molecular targets known as cyclophanes. Cyclophanes have a very rich history however, their immersion in all aspects of chemistry has suffered from a lack of high yielding synthetic techniques, as well as novel methodologies that target substitution on the aliphatic bridges. We have shown that a series of laterally-substituted [2.2]cyclophanes can be synthesized in quantitative yields utilizing template-directed self-assembly. The cyclophanes also exhibit optical properties that are influenced by a nonconventional internal charge transfer process, stemming from the strained cyclobutane core. We have also developed a sonochemical method to produce nanocrystals of cyclophanes, resulting in enhanced and red-shifted emissions.
Overall, the results described herein detail the use of supramolecular chemistry to achieve the formation of target architectures that differ in topology, connectivity, and/or physiochemical properties. The entirety of this thesis represents the undeveloped interplay between traditional synthetic organic chemistry and supramolecular solid-state chemistry. While the precision afforded by the crystalline phase provides access to molecular targets with high fidelity, expansion to multifunctional molecules that are desirable in the context of emergent properties bodes well for the continued development and exploitation of molecular recognition to generate novel functional materials.
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Hlimi, Fouzia. "Cycloaddition de diarylnitrilimines sur des dérivés de la benzodioxine 1,4 et de la benzoxazine-1,4 : regiochimie de la réaction sur un alcene portant un groupe donneur et un groupe accepteur sur la même extrêmité." Besançon, 1987. http://www.theses.fr/1987BESA2018.
Full textAbstract:
La cycloaddition dipolaire 1,3 des diarylnitrilimines sur le benzodioxinne-1,4 carboxylate-2 d'ethyle conduit a des cycloadduits qui apres ouverture donnent des derives de l'aryloxy-4 diphenyl-1,3 pyrazole qui ne sont pas accessibles par une methode classique de synthese de pyrazoles
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LOPPINET, SERANI ANNE. "Etude d'un catalyseur bifonctionnel tautomerique : la 2-(1h)-pyridone. equilibre de tautomerie, synthese de chaines polyamides aromatiques pour l'habillage du catalyseur, activite catalytique." Paris 6, 1997. http://www.theses.fr/1997PA066444.
Full textAbstract:
Le travail presente dans ce memoire est une etude de catalyseurs de la famille des catalyseurs bifonctionnels tautomeriques. Ces catalyseurs ont comme particularite importante d'avoir de nombreux points communs avec les enzymes. C'est en raison de telles proprietes que nous nous sommes interessees a la 2-(1h)-pyridone en particulier ainsi qu'a certain de ses derives. Ces catalyseurs bifonctionnels tautomeriques mettent en jeu, lors de l'etape de catalyse, leur deux formes tautomeres. Il s'agissait donc tout d'abord de connaitre le mieux possible cet equilibre de tautomerie avant de commencer toute etude cinetique. Nous presenterons donc les methodes physico-chimiques que nous avons utilisees dans ce but et les resultats obtenus quant a la position de cet equilibre. Dans un deuxieme temps, nous avons constate dans la litterature que les analogues synthetiques des enzymes avaient tous ete crees dans l'idee d'optimiser la liaison catalyseur-substrat (dans le but d'imiter le complexe enzyme-substrat). Cette optimisation est obtenue la plupart du temps, soit par la creation d'une cavite qui sert a loger le substrat, soit par la preorganisation du milieu reactionnel. Nous avons donc voulu, dans le meme but, habiller la 2-(1h)-pyridone par des chaines laterales. Nous avons choisi l'habillage par des polyamides aromatiques, pour une question de rigidite conformationnelle assuree a la fois par les liaisons peptidiques et par les noyaux benzeniques. Nous avons realise la synthese de ces chaines, qui sera presentee dans ce memoire. Enfin, deux reactions modeles ont ete retenues pour effectuer les etudes catalytiques. Ce sont la mutarotation du tetramethyl-d-glucose et la substitution nucleophile aromatique du fluor par la piperidine. Nous presentons les raisons de ces choix puis les resultats cinetiques que nous avons obtenus pour une serie de catalyseurs : catalyseurs monofonctionnels basiques et catalyseurs bifonctionnels potentiels.
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Gledhill, Karl, L. E. Rhodes, M. Brownrigg, A. K. Haylett, Mojgan Masoodi, Anthony J. Thody, Anna Nicolaou, and Desmond J. Tobin. "Prostaglandin-E2 is produced by adult human epidermal melanocytes in response to UVB in a melanogenesis-independent manner." Wiley, 2010. http://hdl.handle.net/10454/4579.
Full textAbstract:
noErythema occurs in human skin following excessive exposure to ultraviolet radiation (UVR), and this is in part mediated by the vasodilator prostaglandin E2 (PGE2). While keratinocytes are a major source of this pro-inflammatory eicosanoid, epidermal melanocytes (EM) also express some of the cellular machinery required for PGE2 production. The primary aim of this study is to determine whether EM can produce PGE2 and so potentially also contribute to UVR-induced skin inflammation. Furthermore, we investigate the likely pathway by which this PGE2 production is achieved and investigate whether PGE2 production by EM is correlated with melanogenic capacity. Primary cultures of EM were established from nine normal healthy individuals with skin phototype-1 (n=4) and 4 (n=5), and PGE2 production and melanogenic status were assessed. EM produced PGE2 under baseline conditions and this was increased further upon stimulation with arachidonic acid. Moreover, EM expressed cytoplasmic phospholipase A2, cyclooxygenase-1 and cytoplasmic prostaglandin E synthase. However, no EM culture expressed cyclooxygenase-2 under baseline conditions or following arachidonic acid, UVB- or H2O2 treatments. PGE2 production in response to UVB was highly variable in EM cultures derived from different donors but when pooled for skin phototype exhibited a positive correlation only with SPT-1 derived EM. Interestingly, PGE2 production by EM in response to UVB showed no correlation with baseline levels of melanin, tyrosinase expression/activity or tyrosinase-related protein-1 expression. However, there was an apparent negative correlation with baseline expression of dopachrome tautomerase (DCT), a melanogenic enzyme with reported anti-oxidant potential. These findings suggest that EM have the potential to contribute to UVR-induced erythema via PGE2 production, but that this response may be more related to oxidative stress than to their melanogenesis status.
The Wellcome Trust