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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
91

First Supramolecular Fluorescence-Based Assay for Carbonic Anhydrase Inhibitors

Koutnik, Petr 02 November 2016 (has links)
No description available.
92

Carbonic Anhydrase 9 and Radiation Resistance in RCC

Gallino, Daniel R. 04 1900 (has links)
<p>Renal cell carcinoma (RCC) is the most frequently lethal of urological cancers. It arises in the lining of the proximal convoluted tubule of the kidney and is most common in men ages 50–70. Often, partial or radical nephrectomy is needed to effectively treat the disease, leaving patients with reduced kidney function. RCC frequently displays significant radiation resistance, limiting the usefulness of traditional radiation therapy which might spare patients’ normal tissue. The enzyme carbonic anhydrase 9 (CA9), a product of the hypoxia pathway, is found upregulated in the majority of RCC, particularly the clear cell type. It catalyses the dissolution of carbon dioxide into water as bicarbonate and has been linked to increased invasion and migration in RCC tumour cells. The radiation resistance of two RCC cell lines 786-O (human CCRCC) and RAG (murine renal adenocarcinoma) was investigated by the clonogenic assay in the presence of a CA9 inhibitor or silencing RNA. The interference with CA9 by either of these methods significantly sensitizes 786-O cells to the effects of ionizing radiation <em>in vitro</em>. Moreover, fractionation of the dose delivered can increase this sensitization effect. It is hoped that current targeting of CA9 can make radiation therapy a more feasible option in the treatment of RCC.</p> / Master of Science (MSc)
93

ENERGY IN SYMBIOSIS: CARBON FLUX IN ALGAL MUTUALISMS INVOLVING VERTEBRATE AND INVERTEBRATE HOSTS

Graham, Erin R. January 2014 (has links)
Symbiosis has been an important factor in evolution, and continues to drive speciation and allows organisms to fill new ecological niches. Symbiotic relationships in which both partners benefit from the association, or mutualisms, are ubiquitous in both terrestrial and aquatic ecosystems. Many of the symbionts in these associations are photosynthetic algae or cyanobacteria that fix carbon through photosynthesis and translocate a portion of this energy to their hosts. Host organisms utilize this fixed carbon for a variety of physiological processes, including growth and development, thus, photosynthetically-fixed carbon is vital for many hosts. The following chapters will describe carbon fixation and translocation in two algal symbioses: the freshwater association between the alga Oophila and the eggs of Ambystoma maculatum salmanders, and the relationship between the dinoflagellate Symbiodinium and marine zoanthids. These chapters will discuss carbon flux in symbiosis, and reveal some of the ways in which environmental factors alter photosynthesis in algal mutualisms. / Biology
94

CARBONIC ANHYDRASE MODULATORS FOR DETECTION AND TREATMENT OF HUMAN DISEASES

Mondal, Utpal Kumar January 2019 (has links)
Carbonic anhydrases (CAs, EC 4.2.1.1) are a class of metalloenzymes that catalyze the hydration of CO2 under physiologic conditions and are involved in many physiological and pathological processes. Modulation of CA activity, particularly CA inhibition is exploited pharmacologically for the treatment of many diseases such as cancer, glaucoma, edemas, mountain sickness. CA activation has been less frequently investigated till recently. Genetic deficiencies of several CA isozymes are reported in the literature and reflect the important role of carbonic anhydrases in human physiology and homeostasis. Activation of CA isozymes in brain have been correlated recently with spatial learning and memory. Based on these premises, activators of CA isozymes have the potential to alleviate mild dementias and to act as potential nootropic agents. In chapter 3, continuing our long-term interests towards the development of potent and selective CAAs, we carried out X-ray crystallographic studies with a small series of pyridinium histamine derivatives, previously developed as CAAs by our group. This study revealed important insights into the binding of this class of activators into the active site of CA II isozyme. A potent pyridinium histamine CAA 25i was successfully crystallized with CA II isozyme and was found to bind into the hydrophobic region of the active site, with two binding conformations being observed. This is one of the very few X-ray crystal structures of a CAA available. Based on the findings of this X-ray crystallographic study and building on our previously developed ethylene bis-imidazole CAAs, we advanced a novel series of lipophilic bis-imidazoles. Enzymatic assays carried out on purified human CA isozymes revealed several low nanomolar potent activators against various brain-relevant CA isozymes. Bis-imidazole 30e was found to be a nanomolar potent activator for CA IV, CA VA and CA IX. Due to their conjugated structure, these CAAs were also fluorescent and therefore were fully characterized in terms of photophysical properties, with several representatives proving to display very good fluorophores. The very good activation profile against several different CA isozymes, along with excellent fluorescence properties recommend these compounds as great molecular tools for elucidation of role of CA isozymes in brain physiology, as well as towards improvement of memory and learning. Focusing on inhibition of CA isozymes, it must be stressed that over the last decade a clear connection had been established between the expression of CA IX and CA XII and cancer. Since cancer is the second most common cause of death in the world, we explored the possibility to kill cancer cells via inhibition of different CA isozymes present in cancer cells. The membrane bound carbonic anhydrase IX (CA IX) isozyme represents a particularly interesting anticancer target as it is significantly overexpressed in many solid tumors as compared to normal tissues. In malign tissues this CA isozyme was found to play important role in pH homeostasis and promotes tumor cell survival, progression and metastasis. Thus, CA IX represents a potential biomarker and an appealing therapeutic target for the detection and treatment of cancer. CA IX can be targeted either through the development of small or large molecular weight, potent, and selective inhibitors or through the development of CA IX targeted drug delivery systems for selective delivery of potent chemotherapeutic agents. Building on these premises, in this dissertation, we also revealed our continuing efforts towards the development of potent and selective CA IX inhibitors along with their translation into the development of CA IX targeted drug delivery systems. In chapter 4, we designed a series of small molecular weight (MW) ureido 1,3,4-thiadiazole sulfonamide derivatives employing the “tail approach”, through the decoration of established sulfonamide CA inhibitor warheads with different tail moieties via ureido linker. The generated CAIs were tested against tumor associated CA IX and CA XII isozymes and off-target cytosolic isozymes CA I and CA II, and were revealed to be moderate to highly selective and nanomolar, even sub-nanomolar, potent CA IX inhibitors. Several potent pan-inhibitors were also identified in this section. We assessed these CAIs for their in vitro cell killing ability using MDA-MB 231 breast cancer cell line expressing CA IX and CA XII. The most efficient CAI proved to be ureido-1,3,4-thiadiazole-2-sulfonamide 69, which showed subnanomolar potency against purified human CA IX and CA XII isozymes, with good selectivity against CA I and CA II, and consistent, statistically significant cancer cell killing. In Chapter 5, continuing our efforts towards the development of potent and selective CA IX inhibitors, we designed, synthesized, characterized and evaluated a new series of PEGylated 1,3,4-thiadiazole-2-sulfonamide CAIs, bearing different PEG backbone length. We increased the PEG size from 1K to 20K, in order to better understand the impact of the PEG linker length on the in vitro cell killing ability against CA IX expressing cancer cell lines and also against a CA IX negative cell line. In vitro cell viability assays revealed the optimum PEG linker length for this type of bifunctional bis-sulfonamide CAIs in killing the tumor cells. The most efficient PEGylated CAI was found to bis-sulfonamide DTP1K 91, which showed consistent and significant cancer cell killing at concentrations of 10−100 μM across different CA IX and CA XII expressing cancer cell lines. DTP1K 91 did not affect the cell viability of CA IX negative NCI-H23 tumor cells, thus revealing a CA IX mediated cell killing for these inhibitors. In chapter 6, we decided to further explore the possibility of using CA IX as a targeting epitome for the development of a gold nanoparticle-based drug delivery system. We translated the oligoEG- and PEGylated CAI conjugates into efficient targeting ligands for gold nanoparticle decoration along with chemotherapeutic agent doxorubicin (Dox), in a novel multi-ligand gold nanoplatform designed to selectively release the drug intracellularly, in order to enhance the selective tumor drug uptake and tumor killing. We were successful in developing compatible CAI- and Dox- ligands for efficient dual functionalization of gold nanoparticles. Our optimized, CA IX targeted gold nanoplatform was found to be very efficient towards killing HT-29 tumor cells especially under hypoxic conditions, reducing the hypoxia-induced chemoresistance, thus confirmed the potentiating role of CA IX as a targeting epitome. / Pharmaceutical Sciences
95

DEVELOPMENT AND BIOLOGICAL EVALUATION OF CARBONIC ANHYDRASE MODULATORS AS POTENTIAL NOOTROPICS AND ANTICANCER AGENTS

Sanku, Rajesh Kishore kumar January 2018 (has links)
Cancer is the second most common cause of death in the world. One of the objectives of this thesis is to biologically evaluate a series of anti-cancer polymeric aromatic/heterocyclic bis-sulfonamides and pyridinium sulfonamides which were synthesized from three established aminosulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor pharmacophores. Testing of these novel inhibitors and their precursors against a panel of membrane-bound CA isoforms, including tumor-overexpressed CA IX and XII and cytosolic isozymes, identified nanomolar-potent inhibitors against both classes and several compounds with medium isoform selectivity. In the case of pyridinium sulfonamides we used complexes of the inhibitors with cyclodextrins or sulfocalixarene to enhance aqueous solubility for biological testing. The ability of CA inhibitors to kill tumor cells overexpressing CA IX and XII was tested under normoxic and hypoxic conditions, using 2D and 3D in vitro cellular models. The study identified a nanomolar potent PEGylated bis-sulfonamide CA inhibitor (25), as well as cyclodextrin and sulfocalixarenes complexes, which were able to significantly reduce the viability of colon HT-29, breast MDA-MB231, and ovarian SKOV-3 cancer cell lines, thus revealing the potential of polymer conjugates in CA inhibition and cancer treatment. As a different disease state yet still a concern, cognitive dysfunction markedly impacts patients with a host of psychiatric conditions including attention deficit hyperactivity disorder, autism spectrum disorder, drug addiction, schizophrenia, depression, bipolar disorder, obsessive-compulsive disorder, and of course, Parkinson’s and Alzheimer’s diseases and other types of dementia. Another objective of this thesis was to profile several series of bis-imidazoles for physicochemical, in-vitro and in-vivo properties as potential memory and learning enhancers (nootropics). Biological testing on eight isozymes of carbonic anhydrase (CA) present in the human brain revealed compounds with nanomolar potency against at least one membrane bound, cytosolic or mitochondrial CA isozymes, combined with good physicochemical properties. We also identified lead compounds with the ability to rescue experimental animals from drug-induced memory deficits, using an optimized Novel Object Recognition Task (NORT) procedure. / Pharmaceutical Sciences
96

Élaboration d'un cœur d'électrolyseur à conduction protonique à base de phyllosilicates fonctionnant entre 200 et 300 °C pour l'électrolyse de l'eau et l'hydrogénation du gaz carbonique issu de la biomasse / Elaboration of phyllosilicate based protonic conductor heart of electrolyser working at temperatures between 200°C and 300°C for water electrolysis and the hydrogenation of carbonic gas resulting from biomass

Micheletti, Andrea 23 November 2018 (has links)
L'objectif de la thèse est de fabriquer un conducteur protonique à base de phyllosilicates, fonctionnant à une température comprise entre 200°C et 300°C pour la production d'hydrogène d'une part, et l'hydrogénation du CO2 issu de la biomasse d'autre part. Le dépôt sera effectué sur un substrat en acier fritté, mis au point spécifiquement en collaboration avec le fournisseur.Afin d'appréhender les phénomènes régissant la croissance du dépôt et donc, pouvoir optimiser les performances du procédé, un suivi in-situ par spectroscopie d'impédance électrochimique sera effectué pour chaque essai. Ces analyses seront couplées avec d'autres analyses ex-situ (MEB,XPS,...). L'objectif étant de pouvoir contrôler minutieusement les caractéristiques de la couche formée, et reproduire rapidement le procédé à l'échelle industrielle.A la fin de la thèse, les résultats seront intégrés dans le programme SOLARVI, qui vise à stocker l'énergie issue de sources renouvelables pour la production d'hydrogène d'une part, et la transformation du CO2 issu de la biomasse en produits valorisables dans le domaine de l'énergie et dans la chaîne du carbone d'autre part. / This thesis aims at the elaboration of a phyllosilicate-based protonic conductor working at temperatures between 200°C and 300°C for hydrogen production and hydrogenation of CO2 coming from biomass. The deposit will be carried out on a sintered steel alloy, developed with the supplier.In order to understand the phenomena governing the growth of the deposit, an in-situ monitoring will be performed for each test, by electrochemical impedance spectroscopy. These analyses will be coupled with other ex-situ analyses (SEM, XPS...). That will allow us to obtain the good final properties of the protonic layer and quickly bring the process at industrial scale.At the end of the thesis, all results will be integrated within SOLARVI program, which aims at the energy storage coming from renewable sources, by hydrogen prduction and transformation of CO2 into products which could be valorized in energy and chemistry fields.
97

Influ?ncia da laparoscopia e da laparotomia na gasometria, leucometria diferencial e citocinas em modelo de sepse abdominal em ratos

Ara?jo Filho, Irami 27 October 2005 (has links)
Made available in DSpace on 2014-12-17T14:14:03Z (GMT). No. of bitstreams: 1 IramiAF.pdf: 222778 bytes, checksum: 19ba0c4bd484b69016b906c3ab34fc7f (MD5) Previous issue date: 2005-10-27 / Laparoscopic surgery is associated with reduced surgical trauma, and less acute phase response, as compared with open surgery. Cytokines are important regulators of the biological response to surgical and anesthetic stress. The aim of this study was to determine if CO2 pneumoperitoneum would change cytokine expression, gas parameters and leukocyte count in septic rats. Methods: Wistar rats were randomly assigned to five groups: control (anesthesia only), laparotomy, CO2 pneumoperitoneum, cecum ligation and puncture by laparotomy, and laparoscopic cecum ligation and puncture. After 30 min of the procedures, arterial blood samples were obtained to determine leukocytes subpopulations by hemocytometer. TNF&#945;, IL-1&#946;, IL-6 were determined in intraperitoneal fluid (by ELISA). Gas parameters were measured on arterial blood, intraperitoneal and subperitoneal exsudates. Results: Peritoneal TNF&#945;, IL-1&#946; and IL-6 concentrations were lower in pneumoperitoneum rats than in all other groups (p<0.05). TNF&#945;, IL-1&#946; and IL-6 expression was lower in the laparoscopic than in laparotomic sepsis (p<0.05). Rats from laparoscopic cecum ligation and puncture group developed significant hypercarbic acidosis in blood and subperitoneal fluid when compared to open procedure group. Total white blood cells and lymphocytes were significantly lower in laparoscopic cecum ligation and puncture rats than in the laparotomic (p<0.01). Nevertheless, the laparotomic cecum ligation rats had a significant increase in blood neutrophils and eosinophils when compared with controls (p<0.05). Conclusions: This study demonstrates that the CO2 pneumoperitoneum reduced the inflammatory and immune response in an animal model of peritonitis with respect to intraperitoneal cytokines, white blood cell count and clinical correlates of sepsis. The pneumoperitoneum produced hypercarbic acidosis in septic animals / A cirurgia laparosc?pica est? associada com trauma reduzido e baixa resposta metab?lica na fase aguda do trauma, quando comparada com a cirurgia aberta. As citocinas e o balan?o ?cido-base s?o fatores importantes da resposta biol?gica ao trauma cir?rgico-anest?sico. O objetivo deste estudo foi determinar se o pneumoperit?nio com CO altera a express?o das citocinas intraperitoneais, a gasometria do sangue arterial, dos exsudatos intraperitoneal e subperitoneal, e a contagem diferencial de leuc?citos em ratos com sepse abdominal. M?todo: Ratos Wistar foram aleatoriamente distribu?dos em cinco grupos: controle (somente 2anestesia), laparotomia, pneumoperit?nio com CO2, ligadura e pun??o do ceco por laparotomia, ligadura e pun??o do ceco por laparoscopia. Ap?s 30 minutos dos procedimentos, sangue arterial foi colhido para leucometria em hemocit?metro. FNT&#945;, IL-1&#946; e IL-6 foram dosadas no lavado intraperitoneal (por ELISA). Os par?metros gasosos foram medidos no sangue arterial e nos exsudatos intraperitoneal e subperitoneal. Resultados: Os valores de FNT&#945;, IL-1&#946; e IL-6 foram significantemente menores nos ratos submetidos ao pneumoperit?nio do que em todos os outros grupos (p<0.05). Express?o de FNT&#945;, IL-1&#946; e IL-6 foi menor no grupo sepse induzida por laparoscopia do que por laparotomia (p<0.05). Os ratos submetidos ? ligadura e pun??o do ceco por via laparosc?pica desenvolveram acidose hiperc?rbica no sangue arterial e exsudato subperitoneal, mais intensa do que no grupo sepse laparot?mica. Leucopenia e linfopenia foram mais acentuadas no grupo sepse laparosc?pica (p<0.01). Entretanto, os animais submetidos a sepse laparot?mica desenvolveram significante aumento de neutr?filos e eosin?filos quando comparados com os controles (p<0.05). Conclus?es: Este estudo demonstrou que o pneumoperit?nio com CO contribuiu para reduzir a resposta inflamat?ria e imunol?gica em ratos submetidos a modelo de sepse abdominal, no que diz respeito a citocinas intraperitoneais e leucometria diferencial. O pneumoperit?nio tamb?m contribuiu para instala??o de acidose hiperc?rbica nos ratos s?pticos
98

ANÁLISIS DEL POTENCIAL DE LA FERTIRRIGACIÓN CARBÓNICA EN CÍTRICOS

Tarazona Díez, José Vicente 07 January 2016 (has links)
[EN] This research work constitutes a first approximation to the study of the viability of carbonic fertirrigation in citrus fruits as a CO2 drain potential. To that effect, carbonic fertirrigation experiments were carried out with citrus fruits of the Nadarcott variety from the year 2010 to the year 2015. The study required the monitoring of parameters related to the leaf surface, the phenological state of the trees, the ground, the leaves and the fruits of the tested trees. The analysis of the results obtained showed there were no significant differences in the size and quality of the fruits irrigated with CO2. Differences were neither observed in the trees' vegetative development nor in the advance or delay of the blooming and formation of fruits. The analysis of the grounds revealed that the content in organic matter of the grounds irrigated with CO2 was higher than in the grounds used as reference in at least two tenths of a percentage. Similarly, it was noted that the content in iron in the leaves of the trees irrigated with CO2 was significantly higher than in the trees used as reference. The statistical analysis carried out confirmed these conclusions, noting a 24% increase over the average value in the case of the organic matter in the ground and of a 16% in the case of the iron content in the leaves. Both factors indicate that carbonic fertirrigation does have relevant agronomic repercussions, especially on the organic fraction of the ground and on the iron soluble fraction. Various authors confirm the mobilisation of the iron produced by the decrease in the pH of the irrigation water - this study confirms this fact and strengthens the usage of carbon dioxide as a potential substitute of strong acids normally used for this purpose. The increase in the content of the ground's organic matter is an especially interesting result, as it was not expected, even though some authors have related the decrease of soil respiration to different cultural practices that improve the ground's texture. The interaction between the CO2 of the irrigation water and the content in organic matter in the ground and, therefore, soil respiration must be studied in further detail in a future, with experiences specially aimed at valuing the repercussions of this practice on both parameters. / [ES] Este trabajo de investigación constituye una primera aproximación al estudio de viabilidad de la fertirrigación carbónica en cítricos como potencial sumidero de CO2. A tal efecto, se llevaron a cabos experimentos de fertirrigación carbónica con cítricos de la variedad Nadarcott desde el año 2010 hasta el año 2015. El estudio requirió la monitorización de parámetros relacionados con la superficie foliar, los estados fenológicos de los árboles, el suelo, las hojas y los frutos de los árboles ensayados. El análisis de los resultados obtenidos mostró que no había diferencias significativas en el tamaño y calidad de los frutos regados con CO2. Tampoco se observaron diferencias en el desarrollo vegetativo de los árboles ni en el avance o retraso de la floración y formación de los frutos. Los análisis de los suelos revelaron que el contenido en materia orgánica de los suelos regados con CO2 era más alto que los suelos tomados como referencia en al menos dos décimas porcentuales. De la misma manera, se observó que el contenido en hierro en las hojas de los árboles regados con CO2 era significativamente más alto que en los árboles tomados como referencia. Los análisis estadísticos realizados confirmaron estas conclusiones, observándose un incremento del 24% sobre el valor promedio en el caso de la materia orgánica del suelo y del 16% en el caso del contenido en hierro de las hojas. Ambos factores indican que la fertirrigación carbónica sí que tiene repercusiones agronómicas relevantes, especialmente sobre la fracción orgánica del suelo y sobre la fracción soluble de hierro. Diversos autores confirman la movilización del hierro producido por la disminución del pH del agua de riego; este estudio confirma este hecho y refuerza la utilización del dióxido de carbono como potencial sustituto de los ácidos fuertes normalmente utilizados para este cometido. El aumento en el contenido de materia orgánica del suelo es un resultado especialmente interesante, pues no era esperado pese a que algunos autores han relacionado la disminución de la respiración edáfica con diferentes prácticas culturales que mejoran la textura del suelo. La interacción entre el CO2 del agua de riego y el contenido en materia orgánica del suelo y, por tanto, la respiración edáfica deben de ser estudiados con más detalle, en un futuro con experiencias especialmente dirigidas a valorar las repercusiones de esta práctica sobre ambos parámetros. / [CAT] Aquest treball d'investigació constitueix una primera aproximació a l'estudi de la viabilitat de la fertirrigació carbònica en cítrics com a potencial embornal de carboni. Amb aquesta finalitat es dugueren a terme experiments de fertirrigació carbònica amb cítrics de la varietat Nadorcott des de l'any 2010 fins l'any 2015. L'estudi va requerir la monitoratge de paràmetres relacionats amb la superfície foliar, els estat fenològics del arbres, el sòl, les fulles i el fruits dels arbres assatjats. L'anàlisi dels resultats obtinguts mostrà que no hi havia diferències significatives en el tamany i qualitat del fruits regats amb CO2. Tampoc es varen observar diferències en el desenvolupament vegetatiu dels arbres ni en l'avanç o retard de la floració i formació dels fruits. Les anàlisis dels sòls revelaren que el contingut de matèria orgànica dels sòls regats amb CO2 era més alt que els sòls considerats com a referència en, almenys, dues dècimes percentuals. De la mateixa manera, s'observà que el contingut de ferro en les fulles dels arbres regats amb CO2 era significativament més alt que en els arbres referència. Les anàlisis estadístiques realitzades confirmaren aquestes conclusions, observant-se un increment del 24% sobre el valor mitjà en el cas de la matèria orgànica del sòl i del 16% en el cas del contingut en ferro de les fulles. Tots dos factors indiquen que la fertirrigació carbònica sí que té repercusions agronòmiques rellevants, especialment, sobre la fracció orgànica del sòl i la fracció soluble de ferro. Diferents autors confirmen la mobilització del ferro produit per la disminució del pH de l'agua de reg; aquest estudi confirma aquest fet i reforça l'ús del diòxid de carboni com a potencial subsutitut dels àcids forts normalment gastats per a aquesta tasca. L'augment en el contingut de matèria orgànica del sòl és un resultat especialment interessant, ja que no era esperat, malgrat que alguns autors han relacionat la disminució de la respiració edàfica amb diferents pràctiques culturals que milloren la textura del sòl. La interacció entre el CO2 de l'aigua de reg i el contingut en matèria orgànica del sòl i, per tant, la respiració edàfica han de ser estudiats amb més detall en un futur amb experiències especialment dirigides a valorar les repercussions d'aquesta pràctica sobre tots dos paràmetres. / Tarazona Díez, JV. (2015). ANÁLISIS DEL POTENCIAL DE LA FERTIRRIGACIÓN CARBÓNICA EN CÍTRICOS [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/59405 / TESIS
99

Carbonic anhydrase 8 (CAR8) negatively regulates GLP-1 secretion from enteroendocrine cells in response to long-chain fatty acids / 炭酸脱水酵素8(CAR8)は腸管内分泌細胞からの長鎖脂肪酸応答性GLP-1分泌を負に制御する

Fujiwara, Yuta 26 July 2021 (has links)
京都大学 / 新制・論文博士 / 博士(医学) / 乙第13429号 / 論医博第2233号 / 新制||医||1053(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 妹尾 浩, 教授 川口 義弥 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM
100

[en] IMINE-BASED COFS SYNTHESIS AIMING CO2 CAPTURE AND CONVERSION / [pt] SÍNTESE DE COFS BASEADOS EM IMINAS VISANDO A CAPTURA E CONVERSÃO DE CO2

MARCELO FOLHADELLA MARTINS FARIA AZEVEDO 11 January 2022 (has links)
[pt] No contexto da redução da concentração de CO2 na atmosfera e utilizar o mesmo na síntese de produtos de interesse, buscou-se sintetizar COFs com propriedades biomiméticas da enzima anidrase carbônica capaz de converter CO2. O chamado Tppa-NO2-COF foi planejado a partir dos blocos de construção triformilfluoroglucinol e 2-nitro 1,4-fenilenodiamina (comercialmente disponível). O triformilfluoroglucinol foi previamente sintetizado pela reação de Duff, entretanto outras metodologias alternativas foram testadas de forma a melhorar as condições reacionais e o custo atrelado ao processo. Em decorrência da não reprodutibilidade das metodologias sintéticas do Tppa-NO2-COF reportadas na literatura, foi necessário um processo de otimização (variando tipo e quantidade de solvente, concentração do ácido, condição reacional, entre outros). A influência do grupamento nitro no Tppa-NO2 foi igualmente avaliada, através da síntese do material análogo sem o nitro, o chamado Tppa-1-COF, o qual foi obtido com área de 434 m2/g, condizente com o dado reportado na literatura. Outra metodologia abordada para a síntese desses materiais foi a sonificação (sonochemistry) que demonstrou ser uma excelente alternativa para a síntese dos materiais de maneira eficaz e rápida. Entretanto, o material foi obtido com cristalinidade e área específica baixas e muito variáveis (de 40 a 628 m2/g), o que, por definição não pode ser chamado de COF, sendo então tratado como Covalent Organic Network (CON). Apesar da adversidade, seguiu-se com as modificações pós-sintéticas no Tppa-NO2-CON, realizando a redução do grupamento nitro e consequente reação do grupo amina para formar linkers que permitissem a atividade biomimética à enzima via ligação peptídica ou via triazol, capazes de se coordenar ao íon zinco. Otimizações ainda se fazem necessárias para a obtenção do COF, bem como estudos mais aprofundados nas modificações pós sintéticas e de adsorção de CO2, aplicação na conversão de CO2 a bicarbonato e outros produtos de interesse para a síntese orgânica. / [en] In the context of reducing the concentration of CO2 in the atmosphere and using it in the synthesis of products of interest, we sought to synthesize COFs with biomimetic properties of the carbonic anhydrase enzyme capable of converting CO2. The so-called Tppa-NO2-COF was designed from the building blocks triformylfluoroglucinol and 2-nitro 1,4-phenylenediamine (commercially available). Triformylfluoroglucinol was previously synthesized by the Duff reaction, however other alternative methodologies were tested in order to improve the reaction conditions and the cost linked to the process. Due to the non-reproducibility of synthetic methodologies of Tppa-NO2-COF reported in the literature, an optimization process (varying type and amount of solvent, acid concentration, reaction condition, among others) was necessary. The influence of the nitro group on Tppa-NO2 was also evaluated, through the synthesis of an analogous material without nitro, the so-called Tppa-1-COF, which was published with an area of 434 m2/g, consistent with what is reported in the literature. Another approach to synthetic materials for sonification (sonochemistry) includes being an excellent alternative for an efficient and rapid synthesis of materials. However, the material was found with low and highly variable crystallinity and specific area (from 40 to 628 m2/g), which, by definition, cannot be called COF, being treated as Covalent Organic Network (CON). Despite the adversity, post-synthetic modifications in the Tppa-NO2-CON followed, performing the reduction of the nitro group and consequent reaction of the amine group to form ligands that would allow a biomimetic activity to the enzyme via peptide bond or via triazole, from coordinate with the zinc ion. Optimizations are still necessary to obtain the COF, as well as in-depth studies on post-synthetic modifications and CO2 adsorption, application in the conversion of CO2 to bicarbonate and other products of interest to organic synthetic.

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