Universiẗat, Diss., 2005--Würzburg.

Universiẗat, Diss., 2003--Würzburg.

<p> New uranium(VI) complexes of a-hydroxyquinoline ligands of formulae U02(R-Q)2 R-QH have been prepared. In these compounds, the additional liquid is likely bonded as a zwitterion. Appropriate substitution in the 2- and 7-positions lead to interesting steric effects. Some uranium(VI) complexes reported in the literature have been re-examined and found to be incorrectly formulated. </p> <p> The scandium(III) complex of a-hydroxyquinoline obtained from aqueous solution was. found to be Sc(C9H6N0) 3 •H20 and not Sc(CgH&N0) 3 •C 9H7NO as previously reported. In the absence of water, Sc (CgH&NO) 3 •C 9H7NO 'Was obtained. New scandium(III) complexes of formulae Sc(R-Q) 3 •R-QH and Sc(R-Q) 3 •H20 have been prepared. </p> / Thesis / Doctor of Philosophy (PhD)

Synthese und Charakterisierung (Einkristall-Röntgenstrukturanalyse, NMR-spektroskopische Untersuchung im Festkörper und/oder in Lösung, Elementaranalyse) von Verbindungen des fünffach- und sechsfach koordinierten Siliciums sowie einer Verbindung des sechsfach koordinierten Germaniums; Synthese und Charakterisierung (NMR-spektroskopische Untersuchung im Festkörper und/oder in Lösung, Massenspektrometrie, Elementaranalyse) von Silanen sowie Dihydroxamsäuren und deren Monokaliumsalzen. / Synthesis and caracterization (X-ray diffraction, NMR-spektroscopic study in the solid state and/or in solution, elemental analysis) of compounds of fivefold- and sixfold coordinate silicon as well as of one compound of sixfold coordinate germanium; synthesis and caracterization (NMR-spektroskopic study in the solid state and/or in solution, mass spectrometry, elemental analysis) of silanes as well as of dihydroxamic acids and their respective monopotassium salts.

This thesis contributes to the field of silicon chemistry, with a special emphasis on the chemistry of penta- and hexacoordinate silicon.The spirocyclic zwitterionic Lambda5Si-silicates 1–6 with a (2,2,6,6-tetramethylpiperidinio)- methyl group and two identical bidentate chelate ligands derived from glycine, (S)-alanine, (S)-phenylalanine, (S)-valine, (S)-tert-leucine, or (S)-proline bound to the silicon(IV) coordination center were synthesized and structurally characterized for the first time.The hitherto unknown spirocyclic zwitterionic Lambda5Si-silicates 7–12 with an (ammonio)- methyl group and two identical bidentate chelate ligands derived from (S)-lactic acid, (S)-3- phenyllactic acid, or (S)-mandelic acid were synthesized and structurally characterized in the solid state (elemental analyses (C, H, N), crystal structure analyses, 15N and 29Si VACP/MAS solid-state NMR experiments) and in solution (except 10; 1H, 13C, and 29Si NMR experiments)The spirocyclic zwitterionic Lambda5Si-silicates 13, 15, and 16 with an (ammonio)methyl group and two bidentate meso-oxolane-3,4-diolato(2–) ligands bound to the silicon(IV) coordination center were synthesized for the first time. The already existent compound 14 was resynthesized in order to perform a crystal structure analysis. All compounds were characterized by elemental analyses (C, H, N), 29Si VACP/MAS solid-state NMR experiments, and solution NMR studies (1H, 13C, 15N, and 29Si NMR experiments), and compounds 14–16 were additionally studied by single-crystal X-ray diffraction.The already existent zwitterionic Lambda5Si-silicate 17 was synthesized by new methods, including a remarkable Si–C cleavage reaction with benzoin. To investigate the dynamic behavior of the known zwitterionic Lambda5Si-silicate 18 in solution, VT 1H NMR experiments in CD2Cl2 were performed in the temperature range –100 °C to 23 °C.The hexacoordinate silicon compounds 19–22 containing multidentate ligands derived from citric acid or (S)-malic acid were synthesized for the first time. The anionic Lambda6Si-silicates 19–22 were structurally characterized in the solid state by single-crystal X-ray diffraction and VACP/MAS NMR spectroscopy (13C, 15N, 29Si). Upon dissolution in water at 20 °C, spontaneous hydrolysis of the Lambda6Si-silicate anions was observed. / Die vorliegende Arbeit stellt einen Beitrag zur Chemie des penta- und hexakoordinierten Siliciums dar.Erstmalig wurden die spirocyclischen zwitterionischen Lambda5Si-Silicate 1–6 synthetisiert und strukturell charakterisiert. In diesen Verbindungen des pentakoordinierten Siliciums sind eine (2,2,6,6-Tetramethylpiperidinio)methyl-Gruppe und zwei identische zweizähnige Chelat- Liganden, die sich von den &#945;-Aminosäuren Glycin, (S)-Alanin, (S)-Phenylalanin, (S)-Valin, (S)-tert-Leucin oder (S)-Prolin ableiten, an das Si(IV)-Koordinationszentrum gebunden.Die spirocyclischen zwitterionischen Lambda5Si-Silicate 7–12 mit einer (Ammonio)methyl- Gruppe und zwei identischen Chelat-Liganden, die sich von (S)-Milchsäure, (S)-3- Phenylmilchsäure oder (S)-Mandelsäure ableiten, wurden erstmals synthetisiert. Die strukturelle Charakterisierung erfolgte durch Elementaranalysen (C, H, N), Festkörper-NMRSpektroskopie (15N- und 29Si-VACP/MAS-NMR) und durch 1H-, 13C-, 15N- und 29Si-NMRExperimente in Lösung. Die Existenz dieser Verbindungen wurde zusätzlich mittels Röntgenbeugung an Einkristallen bestätigt.Die bisher unbekannten spirocyclischen zwitterionischen Lambda6Si-Silicate 13, 15 und 16 mit einer (Ammonio)methyl-Gruppe und zwei identischen zweizähnigen meso-Oxolan-3,4- diolato(2–)-Liganden wurden synthetisiert. Die bereits bekannte Verbindung 14 wurde zur Anfertigung einer Kristallstrukturanalyse resynthetisiert. Die &#955;5Si-Silicate 13–16 wurden mit Hilfe elementaranalytischer (C, H, N), NMR-spektroskopischer Methoden (29Si-VACP/MASNMR; 1H-, 13C-, 15N- bzw. 29Si-NMR) charakterisiert. Die Verbindungen 14–16 wurden zusätzlich durch Einkristall-Röntgenstrukturanalysen charakterisiert.Das bereits bekannte zwitterionische Lambda5Si-Silicat 17 war über neue Syntheserouten zugänglich, die neben Si–O- auch eine bemerkenswerte Si–C-Bindungspaltungsreaktion unter milden Bedingungen beinhalten. Um mehr über das dynamische Verhalten des bereits bekannten zwitterionischen Lambda5Si-Silicats 18 in Lösung zu erfahren, wurden 1H-VT-NMRExperimente in dem Temperaturbereich zwischen –100 °C und 23 °C durchgeführt.Die hexakoordinierten Verbindungen 19–22 mit mehrzähnigen Liganden, die sich von Zitronensäure oder (S)-Äpfelsäure ableiten, wurden erstmalig synthetisiert. Die anionischen Lambda6Si-Silicate 19–22 wurden durch Einkristall-Röntgenstrukturanalysen und Festkörper-NMRspektroskopische Untersuchungen (13C-, 15N- bzw. 29Si- VACP/MAS-NMR) strukturell charakterisiert. Beim Auflösen der Verbindungen 19–22 in Wasser bei 20 °C wurde jeweils eine spontane Hydrolyse der Lambda6Si-Silicat-Anionen beobachtet.

Biomaterials used in biomedical implants, diagnostic devices, and in-situ sensors, all face the issue of biofouling. Surface modification of biomaterial surfaces with antifouling polymers can prevent non-specific adsorption of proteins and other bio-foulants onto these surfaces. Although there are many antifouling polymers to chose from, getting the polymers onto different materials is challenging as the surface modification process is dependent on the substrate’s surface chemistry. This limits the kinds of materials that are able to be modified, especially in devices made with several materials that must be modified as a single unit. Therefore, the goal of this research is to develop an effective antifouling surface modification that is compatible with different types and classes of biomaterials. A three-step modification approach was taken to form dense antifouling polymer brushes. The surfaces were first activated using oxygen plasma to increase the density of surface hydroxyl groups. Next, a silane coupling agent with an Atom Transfer Radical Polymerization (ATRP) initiator was attached to the activated surfaces. Finally, an antifouling zwitterionic monomer was polymerized on the surface using an aqueous controlled living radical polymerization technique, Surface Initiated - Activators Regenerated by Electron Transfer – Atom Transfer Radical Polymerization (SI-ARGET-ATRP). Two zwitterionic antifouling polymers, poly(carboxybetaine methacrylate) (pCBMA), and poly(sulfobetaine methacrylate) (pSBMA) were investigated. Clinically- and environmentally-relevant materials were studied and include poly(dimethylsiloxane) (PDMS), poly(ether ether ketone) (PEEK), titanium, silicon, and 3D printed stainless steel. Water contact angle (WCA) analysis showed that surfaces modified with zwitterionic polymers became more hydrophilic. WCA analysis may not be suitable for evaluating non-modified 3D printed surfaces due to their poor surface finish, and this material requires further surface topography characterization. Atomic force microscopy (AFM) and ellipsometry showed that the zwitterionic polymer layers did not necessarily have to be thick to produce their hydrophilic effect. AFM also revealed that each step of the surface modification process produced different roughness effects on all of the different surfaces. The zwitterionic layer with the smoother surface tended to better resist bovine serum albumin (BSA) adsorption. Radiolabelled BSA experiments showed reduced fouling on all 2D samples but to different degrees. The pCBMA modification was not successful in preventing BSA fouling on 3D printed 316L stainless steel. Full or partial BSA fouling may be due to the hydrolytic instability of the silane coupling agent, used to form covalent bonds between the antifouling polymers and the different surfaces, although further investigation is required to validate this hypothesis. Improving the long-term stability of silanes or research with other multi-surface compatible coupling agents that have better long-term stability in aqueous solutions should be pursued. / Thesis / Master of Applied Science (MASc)

Avec 800 000 morts par année, les maladies diarrhéiques sont la seconde cause de mortalité chez les enfants de moins de cinq ans. La shigellose, causée par des bactéries Gram négatif appelées Shigella, est l’une des quatre grandes maladies entériques touchant cette population. L’infection naturelle protège contre la réinfection et la composante polysaccharidique du lipopolysaccharide bactérien est la principale cible de l’immunité humorale. Chez S. sonnei, espèce prévalente dans les pays en développement et développés, ce polysaccharide spécifique, à caractère zwitterionique, a pour unité répétitive un disaccharide composé de deux hexosamines rares : l’acide 2-acétamido-2-désoxy-L-altruronique (A) et le 2-acétamido-4-amino-2,4,6-tridésoxy-D-galactose (B, aussi appelé AAT) associés par des liens glycosidiques 1,2-trans (I). ->4-a-L-AltpNAcA-(1->3)-b-D-FucpNAc4N-(1-> (I). Ces travaux s’intègrent dans un programme visant le développement d’un vaccin issu de sucres de synthèse à couverture large contre les infections par Shigella. Le premier objectif de la stratégie développée contre les infections par S. sonnei est l’identification des épitopes saccharidiques, cibles des anticorps protecteurs. Dans ce but, nous avons entrepris la synthèse d’une diversité de fragments du polysaccharide d’intérêt. Des synthèses multi-grammes de précurseurs orthogonalement protégés des monosaccharides A et B ont été mises au point afin d’accéder aux intermédiaires donneurs et accepteurs impliqués dans les étapes de glycosylation. En particulier, deux voies originales d’accès au précurseur B ont été développées. D’autre part, l’optimisation des conditions de glycosylation et d’oxydation a conduit à un bloc disaccharidique AB compatible avec la synthèse d’oligosaccharides d’ordres supérieurs. Les synthons mono- et disaccharidiques identifiés ont été validés à travers l’obtention de quatre disaccharides portant ou non des modifications de la répartition des charges, de deux trisaccharides ainsi que d’un tétrasaccharide. / 800,000 children die each year of diarrhoeal diseases, making it the second cause of death among children under five. Shigellosis, caused by a Gram negative bacterium, Shigella, is one of the four major forms of diarrhoeal diseases in this population. Natural infection protects against reinfection and the humoral response is primarily directed against the specific polysaccharide moiety of the bacterial lipopolysaccharide. S. sonnei, the prevalent species in developed and transitional countries, displays a zwitterionic polysaccharide, whose disaccharide repeating unit is made of two rare aminosugars: a 2-acetamido-2-deoxy-L-altruronic acid (A) and a 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose (B, AAT) 1,2-trans linked to one another (I). ->4-a-L-AltpNAcA-(1->3)-b-D-FucpNAc4N-(1-> (I). This work is part of the program aimed at the development of a synthetic carbohydrate-based broad coverage vaccine against Shigella infections. In order to define the protective epitopes located on the O-specific polysaccharide of S. sonnei, we tackled the synthesis of fragments thereof. First, multigram-scale syntheses of orthogonally protected precursors to residues A and B were undertaken to access donor and acceptor intermediates in the glycosylation reactions. In particular, two original routes to precursors of residue B were developed. Careful optimisation of the glycosylation and oxidation reaction conditions gave the disaccharide building block AB equipped for the synthesis of chain extension at both ends. Selected mono- and disaccharide building blocks were validated by the synthesis of four disaccharides, bearing modification of the charge pattern or not, two trisaccharides and a tetrasaccharide.

Cochlear implants (CIs) help to restore basic auditory function in patients who are deaf or have profound hearing loss. However, CI patients suffer from limited voice and tonal perception due to spatial separation between the stimulating CI electrode and the receptor spiral ganglion neurons (SGNs). Directed regeneration of proximate SGN axons may improve tonal performance and implant fidelity by decreasing the spatial separation between the CI electrode and the neural receptor. Additionally, fibrous scar tissue formation on the surface of implanted electrodes further decreases tonal perception through current attenuation and spreading resulting in late-term hearing loss. Thus, designing surfaces that induce favorable responses from neural tissues will be necessary in overcoming signal resolution barriers. In this work, the inherent spatial and temporal control of photopolymerization was used to functionalize surfaces with topographical and biochemical micropatterns that control the outgrowth of neural and other cell types. First, laminin, a cell adhesion protein was patterned using a photodeactivation process onto methacrylate polymer surfaces and was shown to direct the growth of spiral ganglion neurons (SGN), the primary auditory neural receptors. These protein patterns could even overcome low amplitude/high periodicity competing topographical cues. Additionally, glass substrates were patterned with linear zwitterionic polymers and fibroblasts, astrocytes, and Schwann cells all showed dramatically decreased cell adhesion on 100 µm precocity patterns. Further, SGN neurites showed excellent alignment to these same patterns. Next, poly(dimethyl siloxane) (PDMS) was coated with a crosslinked zwitterionic thin film using a single step photografting/photopolymerization process to covalently bind the hydrogel to PDMS. These coated surfaces showed dramatically lower levels of protein, cell, and bacterial adhesion. Finally, zwitterionic hydrogels were strengthened by changing the concentration of poly(ethylene glycol) diacrylate (PEGDA) and 2-hydroxyethyl methacrylate (HEMA) in the formulation. The direct relationship between changing zwitterionic hydrogel formulation to strengthen the hydrogel and the anti-fouling properties were established. The fundamental understanding and design of cochlear implant materials described herein serves as a foundation for the development of next generation neural prosthetics.

Würzburg, Univ., Diss., 2009

京都大学 / 新制・課程博士 / 博士(理学) / 甲第23020号 / 理博第4697号 / 新制||理||1674(附属図書館) / 京都大学大学院理学研究科化学専攻 / (主査)教授 時任 宣博, 教授 若宮 淳志, 教授 依光 英樹 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM