Τα λιποσώματα αποτελούν ένα από τα πιο διαδεδομένα συστήματα μεταφοράς φαρμάκων. Ένα από τα κυριότερα προβλήματά τους αποτελεί η γρήγορη απομάκρυνσή τους από τον οργανισμό που αντιμετωπίστηκε με την επικάλυψη της επιφάνειάς τους με πολυμερή και κυρίως πολυαιθυλενογλυκόλες (PEG). Η ύπαρξη του PEG στην επιφάνεια αύξησε κατά πολύ τον χρόνο παραμονής των λιποσωμάτων στον οργανισμό αλλά λόγω μειονεκτημάτων, όπως το φαινόμενο αυξημένης εκκαθάρισης απ’τον οργανισμό μετά την δεύτερη δόση όπως και η ύπαρξη πολλών πατεντών, δημιουργούν την ανάγκη για την διερεύνηση νέων μορφών επικάλυψης των λιποσωμάτων. Σκοπός αυτής της εργασίας ήταν η σύνθεση νέων λιπιδικών παραγώγων από κυκλοδεξτρίνες και αιθέρες στέμματος και ο σχηματισμός λιποσωμάτων από αυτά τα παράγωγα. Έναυσμα για την χρήση αυτών των χημικών ουσιών αποτέλεσε η ήδη χρησιμοποίηση τους στην μεταφορά βιοδραστικών ενώσεων καθώς και οι χημικές ιδιότητές τους. Θεωρητικά η ύπαρξη ογκωδών υποκαταστατών στην επιφάνεια των λιποσωμάτων προκαλεί στερεοχημική παρεμπόδιση στις αλληλεπιδράσεις με ουσίες στον οργανισμό, που θα μπορούσαν να προκαλούν την γρήγορη εκκαθάριση από τον οργανισμό, αυξάνοντας έτσι τον χρόνο παραμονής τους. Αρχικά συντέθηκαν τα λιπιδικά παράγωγα από DSPE (δι-στεάρυλοφωσφατιδυλοαιθανολαμίνη) και 18-crown-6-ether καθώς και β-κυκλοδεξτρίνη όμως ο καθαρισμός του παραγώγου με την κυκλοδεξτρίνη δεν κατέστει δυνατός και έτσι σχηματίστηκαν λιποσώματα μόνο από το λιπιδικό παράγωγο του αιθέρα στέμματος. Ως υλικά για την παρασκευή των λιποσωμάτων χρησιμοποιήθηκαν φωσφατιδυλοχολίνη αυγού (egg-PC), το λιπιδικό παράγωγο του αιθέρα, δι-στεάρυλοφωσφατιδυλοαιθανολαμινη-πολυαιθυλενογλυκόλη(DSPE-PEG) και χοληστερόλη (CHOL) Παρασκευάστηκαν με την μέθοδο του λεπτού υμενίου πολυστοιβαδιακά λιποσώματα (MLVs) και με την χρήση υπέρηχων (probe sonicator) μικρά μονοστοιβαδιακά λιποσώματα (SUVs) και στη συνέχεια μελετήθηκε η σταθερότητα αυτών σε ορό αίματος χοίρου (FCS) Επίσης, προκειμένου να αποκτηθούν περισσότερες πληροφορίες για τα λιποσώματα που μελετήθηκαν, πραγματοποιήθηκε προσδιορισμός του μεγέθους καθώς και του ζ-δυναμικού. Η μελέτη σταθερότητας των λιποσωμάτων που περιείχαν το λιπιδικό παράγωγο με τον αιθέρα στέμματος έδειξε ότι σε ποσοστά αντίστοιχα με αυτά του PEG ο αιθέρας στέμματος δεν προσδίδει μεγαλύτερη σταθερότητα. Θα μπορούσε να μελετηθεί μια σειρά λιποσωμάτων με μεγαλύτερο ποσοστό του λιπιδικού παραγώγου ούτως ώστε να αυξηθεί ο όγκος των υποκαταστατών στην επιφάνεια των λιποσωμάτων και συνεπώς η παρεμπόδιση των αλληλεπιδράσεων. / Liposomes are one of the most common drug delivery systems. One of their main problems is their rapid clearance from the blood stream which was encountered by coating the surface with polymers and especially poly-ethylenoglyglycols (PEG). The coating of the surface with PEG increased the time of stay of liposomes in the blood stream but due to disadvantages, such as the phenomenon of increased clearance after the second dose as well as the existence of many patents, created the need for new forms of coating of the liposomes. The main purpose of this thesis was the synthesis of new lipidic derivatives from cyclodextrins and crown ethers as well as the formation of liposomes from these novel derivatives. The reason behind the choice of these chemical substances was that they are already being used in drug delivery as well as their chemical properties. In theory the existence of bulk substituents on the surface of liposomes causes stereochemical hindrance in interactions with substances in the body, which could cause the rapid clearance from the body, thereby increasing the time of stay in the blood stream. Initially lipid derivatives from DSPE (di-stearylophosphatidylethanolamine) and 18-crown-6-ether-and β-cyclodextrin were synthesized but the purification of the cyclodextrin derivative was not made possible and thus liposomes were formed only from the crown ether lipid-derivative. As starting material for the formation of liposomes was used egg phosphatidylcholine (egg-PC), the crown ether lipid-derivative, di-stearylophosphatidylethanolamine- polyethyleneglycol (DSPE-PEG) and cholesterol (CHOL). Multilamellar vesicles (MLVs) were prepared by the thin film method and with the use of ultrasounds (probe sonicator) small unilamellar vesicles (SUVs) were formed, and then their stability in fetal calf serum (FCS) was studied. In addition, in order to obtain more information about the liposomes that were formed, measurements were carried to determine their size as well as magnitude of the z-potential. The study on the stability of liposomes containing the lipid derivative with the crown ether showed that coating of the surface with the crown ether derivative in percentages equivalent to those of PEG does not confer greater stability on the contrary their stability is the same with conventional liposomes. Α study of liposomes with a higher proportion of the lipid derivative in order to increase the bulkiness of the substituents on the surface of the liposomes and thus preventing interactions resulting in the increase of the stability should be considered.

Neste trabalho foi realizada a síntese, purificação e caracterização de uma tetra crowned porfirina, a 5,10,15,20-tetraquis[2-(hexaoxacicloexadecano-3-amidafenil)]-porfirina, H2TCP, bem como a correspondente ferroporfirina, (FeTCP)Cl. Foi investigado a atividade catalítica desta ferroporfirina e da ferroporfirina mono-crowned substituída, (FeMCP)Cl, sintetizada anteriormente, na oxidação dos substratos (z)-ciclooocteno, estireno, cicloexano e do fármaco carbamazepina, por vários oxidantes: iodosilbenzeno, ácido meta-cloroperbenzóico e hipoclorito de sódio, em meio homogêneo (MeOH ou ACN) e bifásico (C2H4Cl2/H2O). Os resultados revelaram que estes sistemas metaloporfirinicos podem ser considerados bons modelos biomiméticos das enzimas citocromo P450, para oxidação dos substrados estudados, levando ao mesmo produto obtido in vivo na oxidação do fármaco carbamazepina, o cabamazepina-epóxido. Os rendimentos dos produtos de oxidação catalisada pelas ferro crowned porfirinas são, na maioria dos casos, mais expressivos do que aqueles observados com as metaloporfirinas amino-substituídas precursoras. Estes resultados indicam que o substituinte éter coroa confere maior estabilidade e reatividade ao catalisador, e leva à maior seletividade, resultado da interação do éter corôa com o substrato, direcionando-o para o sítio catalítico. Uma outra propriedade importante das crowned porfirinas estudadas é sua capacidade de atuar como agente transferidor de fases nas reações em meio bifásico, utilizando hipoclorito de sódio como oxidante. Os resultados catalíticos nestes sistemas mostraram que as unidades éter corôa foram capazes de carregar o oxidante do meio aquoso para o meio orgânico, onde se encontra o substrato. Foram avaliadas também as propriedades destas novas porfirinas e metaloporfirinas em extrair íons metálicos sódio e potássio do meio aquoso para o meio orgânico. As crowned porfirinas foram bastante eficientes na extração destes metais, principalmente utilizando a técnica de extração por fase única, levando a extrações superiores a 90 % do cátion potássio, e mostrando maior seletividade para este cátion, devido ao tamanho adequado da cavidade do éter corôa para ligar este íon. Foi realizada também a caracterização das porfirinas e ferroporfirinas crowned substituídas por voltametria cíclica, visando sua aplicação futura na análise eletroanalítica de íons potássio e/ou sódio. Observou-se que as porfirinas crowned substituídas sofrem reduções mais fáceis e oxidações mais difíceis quando comparadas com as porfirinas precursoras, mostrando o efeito sacador de elétrons dos substituintes éter corôa. Estes resultados ajudam a explicar os melhores resultados catalíticos obtidos com as ferro porfirinas crowned substituídas, mostrando o efeito do éter coroa em formar a metaloporfirina mais eletrofílica e aumentando a reatividade da espécie catalítica. / In this work we carried out the synthesis, purification and characterization of a tetra crowned porphyrin, 5,10,15,20-tetrakis[2- (hexaoxacyclohexanedecane-3-amidephenyl)]porphyrin, H2TCP, and its corresponding ironporphyrin, (FeTCP)Cl. We investigated the catalytic activity of both this ironporphyrin and the previously synthesized mono-crowned substituted (FeMCP)Cl in the oxidation of the substrates Z-cyclooctene, styrene, cyclohexane and the drug carbamazepine by oxidants like iodosylbenzene, metachloroperbenzoic acid and sodium hypochlorite, in homogeneous (methanol or acetonitrile) and biphasic (C2H2Cl2/H2O) media. Our results demonstrated that these metalloporphyrin systems can be considered good biomimetic models of the cytochrome P450 enzymes in the case of the substrates studied herein, since they led to the same product obtained in the in vivo oxidation of carbamazepine, the carbamazepine-epoxide. The product yields obtained in the oxidation reactions catalyzed by the crowned ironporphyrins were, in the majority of the cases, higher than those achieved with the precursor aminosubstituted metalloporphyrins. This indicates that the crown-ether substituent renders the catalyst more stable and reactive, thus leading to higher selectivity. This selectivity results from the interaction between the crown-ether and the substrate, which directs the latter toward the catalytic site. Another important feature of the studied crowned ironporphyrins is their ability to act as phase-transfer agent in the reactions carried out in biphasic medium, using sodium hypochlorite as oxidant. The catalytic results using such a system gave evidence that the crown ether entities were capable of carrying the oxidant from the aqueous to the organic medium, where the substrate was located. We also evaluated the ability of these novel porphyrins and ironporphyrins to extract sodium and potassium ions from aqueous solution to organic medium. The crowned porphyrins were efficient at extracting these metals, especially when the one-phase extraction technique was employed, leading to potassium ion extraction as high as 90 %. The complexes were more selective toward this latter ion due to the fact that the size of the crown ether cavity was more suitable for binding the larger K+. The crowned porphyrins and ironporphyrins were also characterized by cyclic voltammetry, aiming at their future application in the electroanalytical determination of sodium and potassium ions. When compared with the precursor aminosubstituted porphyrins, we observed that the crowned porphyrins undergo reduction more easily, but their oxidation is harder to achieve. This gives evidence of the electronwithdrawing effect of the crownether substituent. These results help explain the better catalytic results obtained with the crowned ironporphyrins, showing that the crown-ether entity must render the metalloporphyrin more electrophilic, thus increasing the reactivity of the active species.

O gás de síntese (Syngas), proveniente do biogás gerado no tratamento anaeróbio de águas residuárias e o CO2 (presente no biogás) surgem como fontes promissoras para a obtenção de produtos de valor agregado nomeados C2-C4, tais como eteno, propileno, butano, metanol e dimetil éter (DME). Neste trabalho, catalisadores de Cu suportados em argila pilarizada foram estudados visando à produção de compostos C2-C4 a partir da hidrogenação do CO e CO2. Da mesma forma, buscou-se otimizar estes catalisadores, tanto para o processo de Fischer-Tropsch quanto para a síntese direta do DME. Primeiramente, foi avaliado o efeito dos agentes pilarizantes Al e Nb para a conversão do metanol em produtos C2-C4. Após a seleção do agente pilarizante, avaliou-se o efeito do teor de cobre (5% e 10% em massa) no catalisador bifuncional de CuZn/V-Al PILC. Finalmente, foi realizada a adição de Ce, Nb, Fe e/ou Co (5% em massa) sobre o catalisador contendo 10% de Cu suportado na argila pilarizada V-Al PILC. As reações de conversão do metanol foram realizadas em temperaturas de 250 ºC - 400 ºC/2h, sob o fluxo de 1,1 mL.h-1. As reações de hidrogenação (CO e CO2) foram realizadas nas temperaturas de 250 ºC e 300 ºC/3h, P= 40 bar e razão de H2/CO=2 e H2/CO2=3. Os catalisadores foram caracterizadas por difração de raios X (DRX) in situ e ex situ, refinamento de Rietveld, fisissorção de N2, análise da composição química (EDX), microscopia eletrônica de varredura (MEV), redução a temperatura programada (RTP-H2), oxidação do cobre com N2O (TPD-N2O), adsorção de piridina gasosa como molécula modelo para a identificação dos sítios ácidos através do FTIR (FTIR-Py), dessorção de amônia a temperatura programada (DTP- NH3), espectroscopia de absorção de raios X e espectroscopia de fotoelétrons excitados por raios X (XPS). O processo de pilarização somado à impregnação de Cu juntamente com Zn, Ce, Nb, Fe e/ou Co produziu catalisadores com diferentes propriedades estruturais e ácidas, as quais favoreceram as conversões do CO e CO2 para produtos C2-C4. O catalisador bimetálico CuFe/V-Al PILC foi o mais ativo em ambas reações de hidrogenação (CO e CO2) e o mais seletivo para a síntese de DME. Os estudos de caracterização mostraram que a baixa seletividade apresentada para a formação de DME está relacionada com a baixa densidade total de sítios ácidos e com a elevada velocidade espacial experimental. / Syngas, a gas mixture produced from biogas generated in the anaerobic treatment of wastewaters, and carbon dioxide (CO2), a biogas constituent, are promising feedstocks for obtaining value-added chemicals known as C2-C4 products, which include ethylene, propylene, butane, methanol, and dimethyl ether (DME). In this work, Cu catalysts supported on pillared clay were studied aiming at producing C2-C4 compounds from hydrogenation of CO and CO2. The studies were conducted toward optimizing the catalysts performance both for Fischer-Tropsch process and direct synthesis of DME. First, the effect of Al and Nb pillared agents on the conversion of methanol to C2-C4 products was evaluated. The pillared agent was selected and further used to evaluate the Cu content (5 to 10 wt.%) effect on the bifunctional CuZn/V Al-PILC catalyst. Finally, the addition of Ce, Nb, Fe and/or Co (5 wt.%) to the 10 wt.% Cu-containing catalyst supported on V-Al PILC pillared clay was studied. The methanol conversion was performed in the temperature range 250 - 400 °C for 2 h under flow of 1.1 mL h-1. The CO and CO2 hydrogenation reactions were carried out at 250 °C and 300 °C, respectively, for 3 h and P = 40 bar using ratios H2/CO = 2 and H2/CO2 = 3. The catalysts were characterized by means of in situ and ex situ X-ray diffraction (XRD), Rietveld refinement, N2 physisorption, chemical composition analysis (EDX), scanning electron microscopy (SEM), temperature-programmed reduction (TPR-H2), Cu oxidation with N2O (TPD-N2O) pyridine adsorption-FTIR spectroscopy (FTIR-Py), temperature-programmed NH3 desorption (TPD-NH3), and X-ray photoelectron spectroscopy (XPS). The pillaring process along with impregnation of Cu with Zn, Ce, Nb, Fe and/or Co produced catalysts with different structural and acidity properties, which favored the conversion of CO and CO2 into C2 -C4 products. The bimetallic CuFe/V-Al-PILC catalyst presented the highest catalytic activity on the CO and CO2 hydrogenation reactions, and best selectivity for DME synthesis. The low selectivity for obtaining DME was revealed to be most likely due to low total acid sites density of catalysts and high experimental spatial velocity.

No description available.

A series of bis(ethene)rhodium(I) complexes of β-diketonates and similar ligands were prepared. The complexes were characterized by elemental analysis, ¹H NMR spectroscopy and mass spectrometry. Crystal structures are reported for bis(η²-ethene)-(1,3(1-ferrocenyl)butanedionato-0.0 ')rhodium(I), 13, (1,5-cyclooctadieiie)(2-acetylphen-oxy-0,0')rhodium(I),18, and some related molecules. [FORMULA OMITTED] The complexes are catalyst precursors for the homogeneous hydrogenation of olefins and the hydrosilylation of ketones. The generated hydrogenation catalysts are effective for the reduction of sterically unhindered carbon-carbon double bonds. These catalysts are active in the presence of alcohol, aromatic and carboxylic acid functional groups on the olefin substrate. The catalysts decompose to give a heterogeneously active rhodium precipitate when reducing olefinic substrates which are too sterically hindered. Study of the hydrosilylation reaction revealed that the complexes generate active hydrosilylation catalysts. A series of optically active ligands were tested for their ability to effect asymmetry in the silyl ether products. The bis(ethene)rhodium(I) complexes are fluxional in the NMR time scale due to the motion of the ethylene ligands. A detailed ¹H NMR study was conducted on one of the complexes, bis(η²-ethene)(2-acetylphenoxy-0,0 ')rhodium(I) 15 to explore the nature of the rearrangement. [FORMULA OMITTED] The ¹H NMR study revealed the presence of two different modes of fluxionality. The first type of motion is intramolecular in nature and is due to the rotation of the ethylene ligands about the rhodium-ethylene bond axis. The second type is intermolecular in nature and is due to exchange of the ethylene ligands. This exchange is a measure of the lability of the ethylene ligands. The system allowed the separate study of the ethylene ligands and ΔG‡ values were obtained for each ligand for both of the exchange processes. The results of the study indicate the independance of the ethylene ligands with respect to both fluxional processes. / Science, Faculty of / Chemistry, Department of / Graduate

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22763号 / 工博第4762号 / 新制||工||1745(附属図書館) / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 高岡 昌輝, 教授 清水 芳久, 准教授 大下 和徹 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

A facile and efficient base-mediated protocol for debromination of vic-dibromides in perfluoroalkyl(aryl) compounds in aqueous medium has been demonstrated. With mild reaction conditions, the developed strategy has a good substrate scope and electron-deficient olefin products were obtained in good yields. A mechanistic explanation of the debromination is offered with three key experimental observations: (1) the reactions are accelerated by the more electron-rich nucleophiles, (2) the reactions are promoted by the more electron poor vic-dibromides in perfluoroalkyl compounds, and (3) the nucleophilic side reaction is preventable. It is evident that the electronic factors strongly dictate vic-dibromides elimination to the perfluorovinyl ethers, which are the precursors for various perfluorinated polymers. The different reaction conditions were tested in implicit solvent (water) conditions, which helped to confirm the E2-like mechanism.

No description available.

CO2 activation and conversion mediated by transition metal (TM) catalysts were investigated. Homogeneous catalysis of the reverse water gas shift reaction CO2+H2→H2O+CO was studied as a means to reduce CO2.  β-diketiminato metal models L'MI ( L' =C3N2H5-; M = first-row TMs) were considered as potential catalysts. The thermodynamics of prototypical reaction pathways were simulated using B3LYP/aug-cc-pVTZ. Results show that middle series metal complexes result in more thermodynamically favorable properties; therefore, more detailed thermodynamic and kinetic studies were carried out for Mn, Fe, and Co complexes. On the other hand, heterogeneous catalysis of the reduction of CO2 to CO was carried out on Fe, Co, Ni, and Cu surfaces, using the PBE functional. Reaction barriers were calculated using the climbing image nudged elastic band method. Late 3d and 4d transition metal ion (Fe, Co, Ni, Cu, Ru, Rh, Pd, and Ag) mediated activation of dimethyl ether was studied to investigate the intrinsic catalytic properties of metals for C-O bond cleavage. A set of density functional theory (DFT) methods (BLYP, B3LYP, M06, M06-L, B97-1, B97-D, TPSS, and PBE) with aug-cc-pVTZ basis sets was calibrated with CCSD(T)/CBS calculations on reaction energies and barriers.

Due to the advancement of global warming internationally, increasing emphasis is being placed on the environmental accountability of everyone from countries to processes. This study presents novel research on the environmental impacts and economic trade-offs for a processes co-producing electricity, methanol, dimethyl ether (DME) and Fischer Tropsch (FT) fuels from different feedstock ratios of biomass, natural gas, and nuclear hydrogen generated through a CuCl cycle are analyzed for operation in Canada to produce transportation fuels. This study also considers the use of carbon capture and sequestration (CCS), the location of the plant in either Ontario and Alberta, and the input ratio of the feedstocks. This combination of carbonless heat and a “carbon neutral” biomass feedstock would contribute to the net reduction of greenhouse gas (GHG) emissions. In Part I of this work, the model for this BGNTL process was developed. This work expands on the model and evaluates the economics and environmental impacts this plant would have in both Ontario and Alberta based on their local costs, resource availability, and current electricity grid contributions. The analysis investigates the effectiveness of the emission reduction of the products and processes when compared to their cost. It is shown that an increase in the ratio of biomass to natural gas in feedstock, the use of a solid oxide fuel cell (SOFC), and the production of additional electricity while reducing the emissions of the process, increases the cost of CO2e avoided. The results show that the BGNTL concept can be an economically attractive way of reducing net transportation sector GHG emissions in both Ontario and Alberta in meaningful quantities. Optimal cases for both biofuel and FT fuel production contain a single output fuel production process, produce fuels over electricity where possible, and use a gas turbine (GT) for the electricity production that occurs. / Thesis / Master of Engineering (MEngr) / This paper examines a system producing a combination of transportation fuels including diesel, gasoline, methanol (MeOH), dimethyl ether (DME) and electricity from biomass, natural gas and hydrogen. The design of the system units used in the process was done in a previous study, this work expands on the design looking specifically at locating the plant in Ontario and Alberta for their raw resources, electricity grids, and current production methods of fuel. Variations of the plant are compared to each other and current fuel and electricity production with an aim of reducing the cost and emissions created while producing and using the fuels. It is found that increasing the amount of biomass used significantly reduces the emissions but does not create a competitive process due to how expensive it is. Results show that this type of system can decrease transportation sector emissions with a similar additional cost as other current alternatives.