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No description available.

Fluorescence spectroscopy has been considered to be one of the most important research techniques in modern analytical chemistry, biochemistry, and biophysics. At present, fluorescence is a dominant methodology widely used in a great number of research domains, including biotechnology, medical diagnostics, genetic analysis, DNA sequencing, flow cytometry, and forensic analysis, to name just a few. In the past decade, with the rapid development of fluorescence microscopy, there has been a considerable growth in applying fluorescence technique to cellular imaging. The distinguished merits of fluorescence techniques, such as high sensitivity, non-invasiveness, low cytotoxicity, low cost, and convenience, make it a promising tool to replace radioactive tracers for most biochemical measurements, avoiding the high expense and difficulties of handling radioactive tracers. Among the wide range of applications of fluorescence technique, fluorescent sensing of various cations and anions is one of the most important and active areas. This dissertation is all about developing fluorescent sensors for physiologically significant ions, including F-, K+, Fe3+, and Ca2+. All of these sensors demonstrate fluorescence "turn-on" response upon interacting with their respective ions, which makes them much more appealing than those based on fluorescence quenching mechanisms. In Chapter II, a novel highly selective fluorescence turn-on F- sensor (FS), comprised of a fluorene platform serving as the chromophore, and two 1,2,3-triazolium groups functioning as the signaling moieties, is described. The function of FS is established on the basis of deprotonation of the C-H bonds of 1,2,3-triazolium groups, which makes FS the first reported anion sensor based on the deprotonation of a C-H bond. Easy-to-prepare test strips were prepared for determining F- in aqueous media, providing an inexpensive and convenient approach to estimate whether the concentration of F- contained in drinking water is at a safe level. Chapter III contains an optimized synthesis of a reported K+-selective group (TAC), and the development of two TAC-based fluorescence turn-on K+ sensors (KS1 and KS2). The synthetic route of TAC is shortened and its overall yield is enhanced from 3.6% to 19.5%. Both KS1 and KS2 exhibited excellent selectivity toward K+ over other physiological metal cations, high sensitivity for K+ sensing, and pH insensitivity in the physiological pH range. Confocal fluorescence microscopy experiments demonstrate that they are capable of sensing K+ within living cells. 2PA determination reveals that KS2 has a desirable 2PA cross section of 500 GM at 940 nm, which makes it a two-photon red-emitting fluorescent sensor for K+. Chapter IV describes the development of a novel BODIPY-based fluorescence turn-on Fe3+ sensor (FeS). FeS is a conjugate of two moieties, a BODIPY platform serving as the fluorophore and a 1,10-diaza-18-crown-6 based cryptand acting as the Fe3+ recognition moiety. FeS displays good selectivity, high sensitivity, reversibility, and pH insensitivity toward Fe3+ sensing. Based on its excellent performance in determining Fe3+ and very low cytotoxicity, FeS was effectively applied to sensing Fe3+ in living cells. In Chapter V, a new BODIPY-based fluorescence turn-on sensor (CaS) was designed and synthesized for selectively and sensitively determining Ca2+. CaS is comprised of two moieties, a BODIPY fluorophore and a Ca2+ complexing unit. CaS demonstrated selective fluorescence turn-on response towards Ca2+ over other biological metal cations. Moreover, CaS exhibited desirable sensitivity for Ca2+ detection, which makes it more suitable for extracellular Ca2+ determination. In addition, CaS was insensitive to the pH of the physiological environment, especially in the pH range of blood and serum. Therefore, CaS has potential to be applied to sensing Ca2+ ions in extracellular environments. Chapter VI discusses potential future work of KS2 and CaS, following the results achieved in this dissertation. Based on the desirable performances of both sensors in sensing their respective ions, future work could largely be focused on their applications in cellular imaging.

A novel cryptand was synthesized which contained a 3,5-disubstituted-4- oxahexacyclo[5.4.1.02,6.03,10.05,9.08,11] dodecane "cage" moiety. In alkali metal picrate extraction experiments the cryptand exhibited high avidity towards Rb+ and Cs+, when compared with the corresponding model compound. A computational study of a series of cage-functionalized cryptands and their alkali metal-complexes was performed. The X-ray crystal structure of a K+-complexed bis-cage-annulated 20-crown-6 was obtained. The associated picrate anion was found to be intimately involved in stabilization of the host-guest complex. The interaction energy between the host-guest complex and picrate anion has been calculated, and the energy thereby obtained has been corrected for basis set superposition error.

L'objectif général de ce projet est d'apporter des données pertinentes sur le devenir de produits pharmaceutiques dans l'environnement, en particulier aux interfaces eau/sol, afin de mieux suivre les conséquences de leurs utilisations et de leurs rejets. A long terme, les enjeux concernent la protection de l'environnement et de la santé publique. Ces travaux portent sur la caractérisation des propriétés de rétention de cinq médicaments dans des sols calcaires de la région Champagne-Ardenne afin d'évaluer notamment leur potentiel transfert vers les milieux aquatiques. Différents paramètres ont été identifiés comme ayant une influence sur leur rétention. La rétention de l'enrofloxacine dépend fortement du pH et de la force ionique, celle du diclofénac des teneurs en CaCO3 et en matière organique des sols qui ont un effet antagoniste sur son adsorption, celle de la carbamazépine et du sulfaméthoxazole est faible sur un sol calcaire, et enfin la rétention du iopamidol est négligeable. Par ailleurs, l'influence des cations métalliques, polluants ubiquistes des sols, sur la rétention des médicaments a également été étudiée. Les expériences de co-adsorption ont montré que la présence de cuivre et de zinc influence significativement la rétention de l'enrofloxacine, conduisant à une augmentation des quantités adsorbées sur le sol via la formation d'un complexe ternaire de surface, et met ainsi en évidence l'importance de prendre en compte l'interaction des médicaments avec les métaux pour une meilleure compréhension de leur comportement dans les sols. Toutefois, aucune influence notable de la présence de cuivre sur la rétention des autres produits pharmaceutiques n'a été observée. / The overall objective of this project is to provide a better knowledge of pharmaceuticals fate in the environment, more particularly at water/soil interfaces, in order to follow the consequences of their use and disposal. The long-term issues concern the protection of the environment and public health. This work focuses on the characterization of retention properties of five pharmaceuticals in calcareous soils of the Champagne-Ardenne region in order to evaluate their potential transfer to water compartments. Various parameters having an influence on their retention were identified. The retention of enrofloxacin is highly affected by pH and ionic strength, diclofenac retention by CaCO3 and organic matter contents of soils which have antagonistic effect on its adsorption, the retention of sulfamethoxazole and carbamazepine is low on a calcareous soil, and iopamidol adsorption is negligible. Moreover, the influence of metal cations, ubiquitous pollutants in soils, on pharmaceuticals retention was also studied. Co-adsorption experiments indicated that the presence of copper and zinc modifies significantly enrofloxacin retention, leading to an increase of adsorbed amounts on the soil via the formation of a ternary surface complex, thus highlighting the importance to take into account the interaction between metals and pharmaceuticals for a better understanding of their behavior in soils. However, no noticeable impact of the presence of copper on other pharmaceuticals retention has been noticed.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20630号 / 工博第4368号 / 新制||工||1679(附属図書館) / 京都大学大学院工学研究科物質エネルギー化学専攻 / (主査)教授 安部 武志, 教授 阿部 竜, 教授 作花 哲夫 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

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3 Abstract Yeast Saccharomyces cerevisiae belongs to important models for alkali-metal-cation homeostasis research. As other cells, certain intracellular content of K+ is necessary for S. cerevisiae, but Na+ or other alkali metal cations (Li+ , Rb+ ) are toxic for yeast cells. Uniporters Trk1 and Trk2 are responsible for K+ accumulation, while efflux of Na+ , Li+ , Rb+ and K+ is ensured by Ena ATPases, Na+ (K+ )/H+ antiporter Nha1 and K+ specific channel Tok1. Several regulators of K+ (Na+ ) transporters are already known, but reciprocal regulation between transporters and overall picture of the maintenance of alkali-metal-cation homeostasis is still unclear. In this work, K+ circulation (simultaneous uptake and export of K+ ) was shown to be important in alkali-metal-cation homeostasis maintenance. K+ circulation is maintained using reciprocal regulation and interactions between K+ exporters and importers. Though obtained results showed that the alkali-metal-cation homeostasis and associated physiological parameters (e.g. membrane potential, cell size, salt sensitivity) are strain specific, Nha1p was verified to be important for cell survival in ever-changing natural environment. Furthermore, two novel positive regulators of Nha1p activity were found, 14-3-3 proteins and Cka1 kinase. 14-3-3 proteins...

In vorliegender Arbeit wurden Synthese, Kristallstruktur und thermisches Verhalten von sauren und basischen Monofluorophosphate untersucht. Es wurden Salze mit Alkalimetall- und N-haltigen Kationen dargestellt und kristallographisch charakterisiert. Die Strukturen dieser Verbindungen wurden dann mit denen der isoelektronischen Hydrogensulfate verglichen. Mit Hilfe des Kationenaustausches und der Gefriertrocknung konnte ein erfolgreicher Syntheseweg fuer diese Verbindungen entwickelt werden. Die Gefriertrocknung hinderte die Abspaltung von HF und Kondensation des Phosphats und ermöglichte die Isolierung der Rohprodukte. Auf diesem Weg gelang die Darstellung der reinen Verbindungen in höherer Ausbeute, so daß es möglich wurde, die Substanzen mit unterschiedlichen Methoden zu untersuchen. Hergestellt und kristallographisch untersucht wurden folgende Verbindungen: - Hydrogenmonofluorophosphate mit × Alkalimetallkationen: Na, K, Rb, Cs × N-haltigen Kationen: NH4, NMe4, NH2Et2, NHEt3, [C(NH2)3], {HOC[NH(CH3)]2}, [H2N(CH2CH2)NH2], - basische Monofluorophosphate: Na2PO3F·10H2O und [C(NH2)3]2PO3F - gemischte Salze: Cs3(NH4)2(HPO3F)3(PO3F)2 und Na5[NMe4](PO3F)3·18H2O. Die Kristallstrukturen zeigen eine Vielzahl an Strukturtypen, definiert durch die Verknüpfung der verzerrten HPO3F Tetraeder über kurze O-H···O Wasserstoffbrückenbindungen zu Ketten, Dimere oder Tetramere. Diese sind ihrerseits über längere N-H···O und Ow-H···O Wasserstoffbrückenbindungen verknüpft. Kompliziertere Strukturmotive sind in den Strukturen der basischen Monofluorophosphate und der gemischten Salze zu finden. Allgemein werden nur Wasserstoffbrückenbindungen des Typs N-H...O und O-H...O gefunden, dagegen werden keine N-H···F Bindungen in den Strukturen beobachtet. Auch ist mehrheitlich keine Isotypie zwischen sauren und basischen Monofluorophosphaten einerseits und den entsprechenden Sulfaten andererseits zu finden. Isotyp sind nur die Strukturen [NMe4]HPO3F·H2O mit [NMe4]HSO4·H2O und Na2PO3F·10H2O mit Na2SO4·10H2O. Interessanterweise wurden genau in einer dieser isotypen Strukturen, nämlich der des Na2PO3F×10H2O, als Ausnahme zwei O-H···F Bindungen gefunden. Die O···F Abstände liegen im Bereich der Abstände der Ow···O Bindungen in der Struktur. Eine Erklärung für das seltene Auftreten von H-Brücken mit Fluor als Akzeptor ist eine fast vollständige Valenz des Fluors durch seine Bindung zum Phosphor. Mehrere Strukturen widerspiegeln diese Tatsache mit der Orientierung der P-F Bindung. Die Bindung wird nach inerten Stellen, wo kein Metall- oder Wasserstoffatom in der Struktur vorhanden ist, ausgerichtet, um ein weiteres Binden des Fluors (Metallkoordination, Wasserstoffbrückenbindung) zu vermeiden. Weiterhin wurde das thermische Verhalten der Verbindungen NaHPO3F, NaHPO3F·2.5H2O, CsHPO3F und [NHEt3]HPO3F untersucht. Dies erfolgte mit dem Ziel, Information über mögliche Phasenübergänge und die unterschiedlichen Zersetzungstypen zu bekommen. Sowohl der Kation wie auch die Anwesenheit von Kristallwasser haben Einfluß auf den thermischen Abbau. Die Na-Verbindungen zeigen eine Zersetzung über mehrere Schritte, die zu unterschiedlichen Endprodukten führt (Na3P3O9 für NaHPO3F und (NaPO3)n für das Hydrat). Im Vergleich dazu zersetzt sich CsHPO3F nach dem Schmelzen direkt zum Endprodukt, ohne stabile Zwischenprodukte zu bilden. Ähnlich verläuft der thermische Abbau der [NHEt3] Verbindung, die sich allerdings mit einem Masseverlust von 92,27%, also ohne Bildung eines signifikanten Endproduktes, vollständig zersetzt. Während des thermischen Abbaus wurde die Freisetzung von HF und H2O bei allen Verbindungen beobachtet, die sich aber bezüglich der Zersetzungstemperatur und -menge zwischen den Substanzen unterscheiden. Es wurden keine Phasenübergänge erster Ordnung beobachtet. Dies war insbesondere für CsHPO3F überraschend, da das isoelektronische Hydrogensulfat mehrere Phasenübergänge aufweist [2]. Das Ausbleiben von Phasenübergängen allgemein und auch für CsHPO3F wird folgendermassen erklärt. Während das Sulfat Bindungsmöglichkeiten an allen vier Ecken des SO4-Tetraeders hat, besitzt der (H)PO3F-Tetraeder nur eine begrenzte Flexibilität wegen der Anwesenheit von Fluor an einer Ecke. Fluor bevorzugt eine "isolierte" Position am Phosphor. Anhand der vorliegenden Ergebnisse kann die Schlußfolgerung gezogen werden, daß Fluor auf Grund seiner niedrigeren Valenz im Vergleich zu Sauerstoff andere strukturelle und funktionelle Charakteristika aufweist. Die Valenzunterschiede zwischen Sauerstoff und Fluor haben einen starken Einfluß auf das Wasserstoffbrückenbindungssystem in den Kristallstrukturen der Hydrogenmonofluorophosphate und folglich auf die "Nicht-Isotypie" zu den Hydrogensulfaten. / In this thesis, the crystal structures and thermal behavior of hydrogen monofluorophosphates and basic monofluorophosphates with alkali metal and N-containing cations were studied. A comparison to the analogous hydrogen sulfates showed interesting structural variations and differences in thermal behavior. Synthesis of the studied monofluorophosphates involved cation exchange and freeze drying. Freeze drying enabled the isolation of raw products by avoiding the escape of HF and consequent phosphate condensation. This method of preparation led to the synthesis of the hydrogen monofluorophosphates with the following cations: - the alkali metals: Na+, K+, Rb+, and Cs+, - N-containing cations: NH4+, [NMe4]+, [NH2Et2]+, [NHEt3]+, [C(NH2)3]+, {HOC[NH(CH3)]2}+, and [H2N(CH2CH2)NH2]2+, and the basic monofluorophoshates, Na2PO3F·10H2O and [C(NH2)3]2PO3F. The following mixed salts were also obtained with partial cation exchange: - Cs3(NH4)2(HPO3F)3(PO3F)2 - Na5[NMe4](PO3F)3·18H2O. In the crystal structures, the HPO3F tetrahedra were hydrogen-bonded to chains, dimers, and tetramers in the structures of the hydrogen monofluorophosphates. Extensive hydrogen bonding in the basic monofluorophosphates due to high amounts of crystal water led to more complicated structural motifs. Limitations on the bonding of fluorine were observed in each of the structures, whether it be metal coordination or hydrogen bonding. The valency of fluorine is filled by its bond to phosphorus and thus, generally, the fluorine atom does not participate in additional bonds. This explains why, for the most part, the hydrogen monofluorophosphates are not isostructural with the hydrogen sulfates. Only three atoms of the tetrahedron instead of four atoms are available for hydrogen bonding, which influences the crystal structure. This was further confirmed by the comparison of the decahydrates, Na2PO3F×10H2O and Na2SO4×10H2O, which are consequently isostructural based on two O-H×××F bonds formed in Na2PO3F·10H2O. These were the only hydrogen bonds found that involved fluorine as an hydrogen acceptor or donor. The investigations on the thermal behavior of NaHPO3F, NaHPO3F·2.5H2O, CsHPO3F, and [NHEt3]HPO3F found no first-order phase transitions. Stepwise decompositions were observed for the sodium salts, which was attributed to the formation of stable intermediates identified with simulated experiments. The Cs and [NHEt3] compounds demonstrated a direct decomposition postmelting. In general, the release of H2O from the melt occured at lower temperatures, while HF escaped at higher temperatures. The temperatures, at which this initially occured, and the first maximum observed were dependent on the cation and the presence of crystal water. The immediate decomposition of CsHPO3F after melting differs from that of the hydrogen sulfate, CsHSO4, which undergoes several phase transitions before decompositon. This suggests that the sulfate has more structural flexibility on the basis of the four oxygen corners of the tetrahedra. In comparison, the monofluorophosphate is limited in its bonding mobility due to the presence of fluorine on one of the tetrahedral vertices. Therefore, phase transitions are not observed prior to decomposition. It was concluded that fluorine functions differently in the crystal structures on the basis of its lower valency. Thus, the difference in valency between fluorine and oxygen affects the hydrogen bonding of the hydrogen monofluorophosphates and thus pervents the expected isotypy of the isoelectronic hydrogen monofluorophosphates and hydrogen sulfates.