From large polycyclic aromatic hydrocarbons to extended aromate-rich networks

The common ground of this study is the development of novel synthetic strategies to extended one-, two- and three-dimensional aromate-rich systems for which a number of applications are envisaged. rnThe point of departure is the synthesis and characterization of highly symmetric macrocyclic PAHs (polycyclic aromatic hydrocarbons) for which various aspects of supramolecular chemistry will be investigated. The versatility of the Yamamoto macrocyclization will be demonstrated on the basis of a set of cyclic trimers that exhibit a rich supramolecular chemistry. 1,10-phenanthroline, triphenylene and ortho-terphenyl building blocks have been successfully assembled to the corresponding macrocycles following the newly developed synthetic route. Scanning-tunneling microscopy (STM) and two-dimensional wide-angle X-ray scattering (2D-WAXS) were used to study the two- and three-dimensional self-assembly, respectively.rnSecondly, the development of chemical approaches to highly shape-anisotropic graphene nanoribbons (GNRs) and related nanographene molecules shall be discussed. Aryl-aryl coupling was used for the bottom-up fabrication of dendronized monomers, polymers and model compounds. Subsequently, these structures were converted into the final graphene material using oxidative (Scholl-type) cyclodehydrogenation. The GNRs thus obtained are characterized by an unprecedented length and lateral extension. The relevance of structural tailoring in the field of well-defined graphene materials is discussed in detail as only the chemical approach provides full geometry control. rnLastly, novel pathways towards the synthesis of extended three-dimensional networks that are dominated by nitrogen-rich motifs will be presented. If porous, these materials hold a great potential in the fields of gas and energy storage as well as for applications in catalysis. Hence, poly(aminal) networks based on melamine as crosslinking unit were synthesized and characterized with respect to the applications mentioned above. As set of conjugated poly(azomethine) networks was investigated regarding their use as a novel class of organic semiconductors for photocatalytic water splitting. The network structures described in this chapter can also be subjected to a controlled pyrolysis yielding mesoporous, nitrogen-rich carbon materials that were evaluated as active component for supercapacitors.rn

Specific enzymatic cleavage and payload release from peptide-based hybrid nanocapsules

Within this thesis, new approaches for the concepts of peptide-polymer conjugates and peptide-based hybrid nanomaterials are investigated. In the first part, the synthesis of a triblock polymer-peptide-polymer is carried out following a typical peptide coupling reaction, both in solution and on solid-phase. The peptide sequence is chosen, so that it is cleaved by an enzyme preparation of trypsin. End-functionalized polystyrene is used as a model hydrophobic polymer and coupled to the peptide sequence. The results show successful coupling reactions in both methods, while the solid phase method produced a more defined product. Suspensions, consisting of peptide-polymer conjugates particles, are prepared in water by ultrasonication. In contact with the enzyme, the peptide constituting the conjugated particles is cleaved. This demonstrates the enzymatic cleavage in heterophase of enzymatic sequence bond to hydrophobic polymers, and is of great interest for the encapsulation and delivery of hydrophobic molecules.rnA second approach is the preparation of peptide-based hybrid nanocapsules. This is achieved by interfacial polyaddition in inverse miniemulsion with the peptide sequence functionalized with additional amino acids. A method suitable to the use of a peptide sequence for interfacial polyaddition was developed. It is shown that, the polarity of the dispersed phase influences the structures prepared, from particle-like to polymeric shell with a liquid core.rnThe peptide sequence is equipped with a FRET pair (more exactly, an internally-quenched fluorescent system) which allows the real-time monitoring of the enzymatic cleavage of the recognition site. This system shows the successful cleavage of the peptide-based nanocapsules when trypsin preparation is added to the suspensions. A water-soluble fluorescent polymer is efficiently entrapped and its possible use as marker for the capsules is highlighted. Furthermore, a small water-soluble fluorescent dye (SR-101) is successfully encapsulated and the encapsulation efficiency as a function of the functionality of the peptide and the amount of comonomer equivalent (toluene diisocyanate) is studied. The dye is encapsulated at such a high concentration, that self-quenching occurs. Thus, the release of the encapsulated dye triggered by the enzymatic cleavage of the peptide results in a fluorescence recovery of the dye. The fluorescence recovery of the FRET pair in the peptide and of the encapsulated dye correlate well.rnFinally, nanocapsules based on a hepsin-cleavable peptide sequence are prepared. Hepsin is an enzyme, which is highly upregulated in prostate cancer cells. The cleavage of the nanocapsules is investigated with healthy and “cancerous” (hepsin-expressing) cell cultures. The degradation, followed via fluorescence recovery of the FRET system, is faster for the suspensions introduced in the hepsin expressing cell cultures.rnIn summary, this work tackles the domain of responsive nanomaterials for drug delivery from a new perspective. It presents the adaptation of the miniemulsion process for hybrid peptide-based materials, and their successful use in preparing specific enzyme-responsive nanoparticles, with hydrophilic payload release properties.rn

Fluorenbasierende amphiphile Kammpolymere zur Ausbildung definierter Strukturen an Oberflächen und in Lösungen

Die Dissertation beschreibt die Darstellung und Charakterisierung von neuartigen, amphiphilen Carbazol- und Fluoren-(co)-polymeren, die infolge ihres strukturellen Aufbaus sowohl selbstorganisierende als auch optoelektronische Eigenschaften kombinierten. Zum einen wurden Kammpolymere mit konjugierten, steifen Rückgraten und flexiblen sowie konformativ schaltbaren Polyelektrolytseitenketten dargestellt und auf eine pH-abhängige Selbstorganisation in Lösung und an Oberflächen untersucht. Des Weiteren wurden neutrale, methanollösliche Polyfluorene synthetisiert, die in Kombination mit einem unpolaren Polyindenofluorenderivat zum Aufbau mehrschichtiger PLEDs mittels nasschemischer Verfahren eingesetzt wurden. Zum anderen fand die Synthese von amphiphilen Polyfluorenen statt, die als Emulgatoren zur Stabilisierung von inversen Emulsionen eingesetzt wurden. Dabei konnten mit Hilfe eines bereits für die Darstellung von anorganisch-organischen Kern-Schale-Partikeln etablierten in situ-Verfahrens formanisotrope, kristalline Zinkoxidkerne mit konjugierter Polymerhülle erhalten werden.

Developments for transactinide chemistry experiments behind the gas-filled separator TASCA

Topic of this thesis is the development of experiments behind the gas-filled separator TASCA(TransActinide Separator and Chemistry Apparatus) to study the chemical properties of the transactinide elements.rnIn the first part of the thesis, the electrodepositions of short-lived isotopes of ruthenium and osmium on gold electrodes were studied as model experiments for hassium. From literature it is known that the deposition potential of single atoms differs significantly from the potential predicted by the Nernst equation. This shift of the potential depends on the adsorption enthalpy of therndeposited element on the electrode material. If the adsorption on the electrode-material is favoured over the adsorption on a surface made of the same element as the deposited atom, the electrode potential is shifted to higher potentials. This phenomenon is called underpotential deposition.rnPossibilities to automatize an electro chemistry experiment behind the gas-filled separator were explored for later studies with transactinide elements.rnThe second part of this thesis is about the in-situ synthesis of transition-metal-carbonyl complexes with nuclear reaction products. Fission products of uranium-235 and californium-249 were produced at the TRIGA Mainz reactor and thermalized in a carbon-monoxide containing atmosphere. The formed volatile metal-carbonyl complexes could be transported in a gas-stream.rnFurthermore, short-lived isotopes of tungsten, rhenium, osmium, and iridium were synthesised at the linear accelerator UNILAC at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The recoiling fusion products were separated from the primary beam and the transfer products in the gas-filled separator TASCA. The fusion products were stopped in the focal plane of TASCA in a recoil transfer chamber. This chamber contained a carbon-monoxide – helium gas mixture. The formed metal-carbonyl complexes could be transported in a gas stream to various experimental setups. All synthesised carbonyl complexes were identified by nuclear decay spectroscopy. Some complexes were studied with isothermal chromatography or thermochromatography methods. The chromatograms were compared with Monte Carlo Simulations to determine the adsorption enthalpyrnon silicon dioxide and on gold. These simulations based on existing codes, that were modified for the different geometries of the chromatography channels. All observed adsorption enthalpies (on silcon oxide as well as on gold) are typical for physisorption. Additionally, the thermalstability of some of the carbonyl complexes was studied. This showed that at temperatures above 200 °C therncomplexes start to decompose.rnIt was demonstrated that carbonyl-complex chemistry is a suitable method to study rutherfordium, dubnium, seaborgium, bohrium, hassium, and meitnerium. Until now, only very simple, thermally stable compounds have been synthesized in the gas-phase chemistry of the transactindes. With the synthesis of transactinide-carbonyl complexes a new compound class would be discovered. Transactinide chemistry would reach the border between inorganic and metallorganic chemistry.rnFurthermore, the in-situ synthesised carbonyl complexes would allow nuclear spectroscopy studies under low background conditions making use of chemically prepared samples.

Light-sensitive polymeric nanoparticles based on photo-cleavable chromophores

Der Fokus dieser Arbeit liegt in dem Design, der Synthese und der Charakterisierung neuartiger photosensitiver Mikrogele und Nanopartikel als potentielle Materialien für Beladungs- und Freisetzungsanwendungen. Zur Realisierung dieses Konzepts wurden verschiedene Ansätze untersucht.Es wurden neuartige niedermolekulare lichtspaltbare Vernetzermoleküle auf der Basis von o-Nitrobenzylderivaten synthetisiert, charakterisiert und zur Herstellung von photosensitiven PMMA und PHEMA Mikrogelen verwendet. Diese sind unter Bestrahlung in organischen Lösungsmitteln quellbar und zersetzbar. Durch die Einführung anionischer MAA Gruppen in solche PHEMA Mikrogele wurde dieses Konzept auf doppelt stimuliresponsive p(HEMA-co-MAA) Mikrogele erweitert. Hierbei wurde ein pH-abhängiges Quellbarkeitsprofil mit der lichtinduzierten Netzwerkspaltung in wässrigen Medien kombiniert. Diese duale Sensitivität zu zwei zueinander orthogonalen Reizen stellt ein vielversprechendes Konzept zur Kombination einer pH-abhängigen Beladung mit einer lichtinduzierten Freisetzung von funktionellen Substanzen dar. Desweiteren wurden PAAm Mikrogele entwickelt, welche sowohl eine Sensitivität gegenüber Enzymen als auch Licht aufweisen. Dieses Verhalten wurde durch die Verwendung von (meth-)acrylatfunktionalisierten Dextranen als polymere Vernetzungsmoleküle erreicht. Das entsprechende stimuliresponsive Profil basiert auf der enzymatischen Zersetzbarkeit der Polysaccharid-Hauptkette und der Anbindung der polymerisierbaren Vinyleinheiten an diese über photospaltbare Gruppen. Die gute Wasserlöslichkeit der Vernetzermoleküle stellt einen vielversprechenden Ansatz zur Beladung solcher Mikrogele mit funktionellen hydrophilen Substanzen bereits während der Partikelsynthese dar. Ein weiteres Konzept zur Beladung von Mikrogelen basiert auf der Verwendung von photolabilen Wirkstoff-Mikrogel Konjugaten. In einem ersten Schritt zur Realisierung solch eines Ansatzes wurde ein neuartiges Monomer entwickelt. Hierbei wurde Doxorubicin über eine lichtspaltbare Gruppe an eine polymerisierbare Methacrylatgruppe angebunden. Für die Freisetzung hydrophober Substanzen in wässrigen Medien wurden polymere Photolack-Nanopartikel entwickelt, welche sich unter Bestrahlung in Wasser zersetzen. Die lichtinduzierte Änderung der Hydrophobizität des Polymers ermöglichte die Freisetzung von Nilrot durch das Auflösen der partikulären Struktur. Ein interessanter Ansatz zur Verhinderung einer unkontrollierten Freisetzung funktioneller Substanzen aus Mikrogelen ist die Einführung einer stimuliresponsiven Schale. In diesem Kontext wurden Untersuchungen zur Bildung von nicht-stimulisensitiven Schalen um vorgefertigte Mikrogelkerne und zur Synthese von Hydrogelkernen in vorgefertigten polymeren Schalen (Nanokapseln) durchgeführt.

Granulite facies metamorphism and partial melting processes in the Ivrea Zone, Northern Italy

The Ivrea Zone in northern Italy has been the focus of numerous petrological, geochemical and structural studies. It is commonly inferred to represent an almost complete section through the mid to lower continental crust, in which metamorphism and partial melting of the abundant metapelites was the result of magmatic underplating by a large volume of mantle-derived magma. This study concerns amphibolite and granulite facies metamorphism in the Ivrea Zone with focus on metapelites and metapsammites/metagreywackes from Val Strona di Omegna and metapelites from Val Sesia and Val Strona di Postua, with the aim to better constrain their metamorphic evolution as well as their pressure and temperature conditions via phase equilibria modelling.rnrnIn Val Strona di Omegna, the metapelites show a structural and mineralogical change from mica-schists with the common assemblage bi-mu-sill-pl-q-ilm ± liq at the lowest grades, through metatexitic migmatites (g-sill-bi-ksp-pl-q-ilm-liq) at intermediate grades, to complex diatexitic migmatites (g-sill-ru-bi-ksp-pl-q-ilm-liq) at the highest grades. Within this section several mappable isograds occur, including the first appearance of K-feldspar in the metapelites, the first appearance of orthopyroxene in the metabasites and the disappearance of prograde biotite from the metapelites. The inferred onset of partial melting in the metapelites occurs around Massiola. The prograde suprasolidus evolution of the metapelites is consistent with melting via the breakdown of first muscovite then biotite. Maximum modelled melt fractions of 30–40 % are predicted at the highest grade. The regional metamorphic field gradient in Val Strona di Omegna is constrained to range from conditions of 3.5–6.5 kbar at T = 650–730 °C to P > 9 kbar at T > 900 °C. The peak P–T estimates, particularly for granulite facies conditions, are significantly higher (around 100 °C) than those of most previous studies. In Val Sesia and Val Strona di Postua to the south the exposure is more restricted. P–T estimates for the metapelites are 750–850 °C and 5–6.5 kbar in Val Sesia and approximately 800–900 °C and 5.5–7 kbar in Val Strona di Postua. These results show similar temperatures but lower pressure than metapelites in Val Strona di Omegna. Metapelites in Val Sesia in contact with the Mafic Complex exhibit a metatexitic structure, while in Val Strona di Postua diatexitic structures occur. Further, metapelites at the contact with the Mafic Complex contain cordierite (± spinel) that overprint the regional metamorphic assemblages and are interpreted to have formed during contact metamorphism related to intrusion of the Mafic Complex. The lower pressures in the high-grade rocks in Val Sesia and Val Strona di Postua are consistent with some decompression from the regional metamorphic peak prior to the intrusion of the Mafic Complex, suggesting the rocks followed a clockwise P–T path. In contrast, the metapelites in Val Strona di Omegna, especially in the granulite facies, do not contain any cordierite or any evidence for a contact metamorphic overprint. The extrapolated granulite facies mineral isograds are cut by the rocks of the Mafic Complex to the south. Therefore, the Mafic Complex cannot have caused the regional metamorphism and it is unlikely that the Mafic Complex occurs in Val Strona di Omegna.

Uptake of gold nanoparticles in microvascular endothelial cells

The physicochemical properties of nanoparticles make them suitable for biomedical applications. Due to their ‘straight-forward’ synthesis, their known biocompatibility, their strong optical properties, their ability for targeted drug delivery and their uptake potential into cells gold nanoparticles are highly interesting for biomedical applications. In particular, the therapy of brain diseases (neurodegenerative diseases, ischemic stroke) is a challenge for contemporary medicine and gold nanoparticles are currently being studied in the hope of improving drug delivery to the brain.rnIn this thesis three major conclusions from the generated data are emphasized.rn1. After improvement of the isolation protocol and culture conditions, the formation of a monolayer of porcine brain endothelial cells on transwell filters lead to a reproducible and tight in vitro monoculture which exhibited in vivo blood brain barrier (BBB) characteristics. The transport of nanoparticles across the barrier was studied using this model.rn2. Although gold nanoparticles are known to be relatively bioinert, contaminants of the nanoparticle synthesis (i.e. CTAB or sodium citrate) increased the cytotoxicity of gold nanoparticles, as shown by various publications. The results presented in this thesis demonstrate that contaminants of the nanoparticle synthesis such as sodium citrate increased the cytotoxicity of the gold nanoparticles in endothelial cells but in a more dramatic manner in epithelial cells. Considering the increased uptake of these particles by epithelial cells compared to endothelial cells it was demonstrated that the observed decrease of cell viability appeared to be related to the amount of internalized gold nanoparticles in combination with the presence of the contaminant.rn3. Systematically synthesized gold nanoparticles of different sizes with a variety of surface modifications (different chemical groups and net charges) were investigated for their uptake behaviour and functional impairment of endothelial cells, one of the major cell types making up the BBB. The targeting of these different nanoparticles to endothelial cells from different parts of the body was investigated in a comparative study of human microvascular dermal and cerebral endothelial cells. In these experiments it was demonstrated that different properties of the nanoparticles resulted in a variety of uptake patterns into cells. Positively charged gold nanoparticles were internalized in high amounts, while PEGylated nanoparticles were not taken up by both cell types. Differences in the uptake behavior were also demonstrated for neutrally charged particles of different sizes, coated with hydroxypropylamine or glucosamine. Endothelial cells of the brain specifically internalized 35nm neutrally charged hydroxypropylamine-coated gold nanoparticles in larger amounts compared to dermal microvascular endothelial cells, indicating a "targeting" for brain endothelial cells. Co-localization studies with flotillin-1 and flotillin-2 showed that the gold nanoparticles were internalized by endocytotic pathways. Furthermore, these nanoparticles exhibited transcytosis across the endothelial cell barrier in an in vitro BBB model generated with primary porcine brain endothelial cells (1.). In conclusion, gold nanoparticles with different sizes and surface characteristics showed different uptake patterns in dermal and cerebral endothelial cells. In addition, gold nanoparticles with a specific size and defined surface modification were able to cross the blood-brain barrier in a porcine in vitro model and may thus be useful for controlled delivery of drugs to the brain.

Mass spectrometric identification of Varicella-Zoster Virus (VZV) proteins recognized by human T cells

Primary varicella-zoster virus (VZV) infection during childhood leads to varicella commonly known as chickenpox. After primary infection has occurred VZV establishes latency in the host. During subsequent lifetime the virus can cause reactivated infection clinically known as herpes zoster or shingles. In immunodeficient patients’ dissemination of the virus can lead to life-threatening disease. Withdrawal of acyclovir drug prophylaxis puts allogeneic hematopoietic stem-cell transplantation (HSCT) patients at increased risk for herpes zoster as long as VZV-specific cellular immunity is impaired. Although an efficient live attenuated VZV vaccine for zoster prophylaxis exists, it is not approved in immunocompromised patients due to safety reasons. Knowledge of immunogenic VZV proteins would allow designing a noninfectious nonhazardous subunit vaccine suitable for patients with immunodeficiencies. The objective of this study was to identify T cell defined virus proteins of a VZV-infected Vero cell extract that we have recently described as a reliable antigen format for interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assays (Distler et al. 2008). We first separated the VZV-infected/-uninfected Vero cell extracts by size filtration and reverse-phase high performance liquid chromatography (RP-HPLC). The collected fractions were screened for VZV reactivity with peripheral blood mononuclear cells (PBMCs) of VZV-seropositive healthy individuals in the sensitive IFN-γ ELISpot assay. Using this strategy, we successfully identified bioactive fractions that contained immunogenic VZV material. VZV immune reactivity was mediated by CD4+ memory T lymphocytes (T cells) of VZV-seropositive healthy individuals as demonstrated in experiments with HLA blockade antibodies and T cell subpopulations already published by Distler et al. We next analyzed the bioactive fractions with electrospray ionization mass spectrometry (ESI-MS) techniques and identified the sequences of three VZV-derived proteins: glycoprotein E (gE); glycoprotein B (gB), and immediate early protein 62 (IE62). Complementary DNA of these identified proteins was used to generate in vitro transcribed RNA for effective expression in PBMCs by electroporation. We thereby established a reliable and convenient IFN-γ ELISPOT approach to screen PBMCs of healthy donors and HSCT patients for T cell reactivity to single full-length VZV proteins. Application in 10 VZV seropositive healthy donors demonstrated much stronger recognition of glycoproteins gE and gB compared to IE62. In addition, monitoring experiments with ex vivo PBMCs of 3 allo-HSCT patients detected strongly increased CD4+ T cell responses to gE and gB for several weeks to months after zoster onset, while IE62 reactivity remained moderate. Overall our results show for the first time that VZV glycoproteins gE and gB are major targets of the post-transplant anti-zoster CD4+ T cell response. The screening approach introduced herein may help to select VZV proteins recognized by memory CD4+ T cells for inclusion in a subunit vaccine, which can be safely used for zoster prophylaxis in immunocompromised HSCT patients.

Fyn kinase targets in oligodendroglial physiology and myelination

In the central nervous system (CNS), oligodendrocytes form the multilamellar and compacted myelin sheath by spirally wrapping around defined axons with their specialised plasma membrane. Myelin is crucial for the rapid saltatory conduction of nerve impulses and for the preservation of axonal integrity. The absence of the major myelin component Myelin Basic Protein (MBP) results in an almost complete failure to form compact myelin in the CNS. The mRNA of MBP is sorted to cytoplasmic RNA granules and transported to the distal processes of oligodendrocytes in a translationally silent state. A main mediator of MBP mRNA localisation is the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 which binds to the cis-acting A2 response element (A2RE) in the 3’UTR of MBP mRNA. A signalling cascade had been identified that triggers local translation of MBP at the axon-glial contact site, involving the neuronal cell adhesion molecule (CAM) L1, the oligodendroglial plasma membrane-tethered Fyn kinase and Fyn-dependent phosphorylation of hnRNP A2. This model was confirmed here, showing that L1 stimulates Fyn-dependent phosphorylation of hnRNP A2 and a remodelling of A2-dependent RNA granule structures. Furthermore, the RNA helicase DDX5 was confirmed here acting together with hnRNP A2 in cytoplasmic RNA granules and is possibly involved in MBP mRNA granule dynamics.rnLack of non-receptor tyrosine kinase Fyn activity leads to reduced levels of MBP and hypomyelination in the forebrain. The multiadaptor protein p130Cas and the RNA-binding protein hnRNP F were verified here as additional targets of Fyn in oligodendrocytes. The findings point at roles of p130Cas in the regulation of Fyn-dependent process outgrowth and signalling cascades ensuring cell survival. HnRNP F was identified here as a novel constituent of oligodendroglial cytoplasmic RNA granules containing hnRNP A2 and MBP mRNA. Moreover, it was found that hnRNP F plays a role in the post-transcriptional regulation of MBP mRNA and that defined levels of hnRNP F are required to facilitate efficient synthesis of MBP. HnRNP F appears to be directly phosphorylated by Fyn kinase what presumably contributes to the initiation of translation of MBP mRNA at the plasma membrane.rnFyn kinase signalling thus affects many aspects of oligodendroglial physiology contributing to myelination. Post-transcriptional control of the synthesis of the essential myelin protein MBP by Fyn targets is particularly important. Deregulation of these Fyn-dependent pathways could thus negatively influence disorders involving the white matter of the nervous system.rnrn

Hyperbranched polyglycerols as building blocks for complex amphiphilic structures: synthesis, characterization and applications

Among hyperbranched polymers, polyglycerol is one of the most promising and commonly used macromolecules due to its biocompatibility and versatility. However, the synthesis of high molecular weight polyglycerols still involves many intricacies and has only been understood to a limited extent. Furthermore, only few complex structures like star or block copolymers incorporating polyglycerol have been realized so far. Particularly biocompatible block copolymers are considered promising candidates for biomedical applications.rnThe scope of this thesis was the enhancement of the synthetic process leading to polyglycerol derivatives which implies improved molecular weight control for a broad molecular weight range as well as the assembly of more complex structures like amphiphilic block copolymers. Further insight into the relation between reaction solvent, degree of deprotonation during the ring-opening multibranching polymerization of glycidol and the characteristics of the obtained polymers were achieved within the scope of this work. Based on these results, a novel concept for the preparation of hyperbranched polyglycerols with molecular weights up to 20,000 g/mol was developed, applying a two step synthesis pathway. Starting from a partially deprotonated TMP core, low molecular weight hb-PGs were prepared using the known synthetic protocol that has been established since the late 1990ies. In a subsequent reaction sequence, these well defined polymers were used as hyperbranched macroinitiator cores in order to obtain high molecular weight hb-PGs with remarkably low polydispersity (Mw/Mn < 1.8). Molecular weight control was shown to be excellent and undesired low molecular weight side products were absent. Furthermore, the technique of continuous spin fractionation has been discovered as an efficient method for polyglycerol work-up to remove quantitatively residual monomer- and oligomer traces from hb-PG compositions to result in samples with significantly reduced polydispersities. Based on these results the synthesis of amphiphilic block copolymers containing hydrophilic hyperbranched polyglycerol blocks and linear, apolar poly(propylene oxide) blocks has been significantly improved and augmented to hb-PG-b-l-PPO-b-hb-PG ABA block copolymers. The influence of different polyglycerol-based amphiphiles on the fibril formation was studied by Thioflavin T Fluorescence showing remarkable increasing lag times which is promising in order to enhance the stability of this protein. In addition the first synthesis of poly(glyceryl glycerols) (PGG), introducing a new solketyl glycidyl ether monomer (IGG) was shown. It was furthermore demonstrated that core-functional carbosilane wedges allow application in block copolymer synthesis. Bisglycidolized amine functional polymers were successfully employed as macroinitiators for glycidol polymerization. This resulted in the first example of amphiphilic hyperbranched-hyperbranched polymer structures. Finally, it has been shown that the previously reported synthetic pathway to carboxylated hyperbranched polyglycerol polyelectrolytes can also be applied for the amphiphilic linear-hyperbranched block copolymers. These novel biocompatible and highly amphiphilic polyelectrolytes offer great potential for further investigations. rnrn

Wet chemistry synthesis towards nanostructures of thermoelectric antimonides

Die vorliegende Arbeit befasst sich mit der Synthese von nanostrukturierten Antimoniden, wobei die folgenden beiden Themen bearbeitet wurden: rnAus chemischer Sicht wurden neue Synthesewege entwickelt, um Nanopartikel der Verbindungen in den binären Systemen Zn-Sb und Fe-Sb herzustellen (Zn4Sb3, ZnSb, FeSb2, Fe1+xSb). Anders als in konventionellen Festkörperreaktionen, die auf die Synthese von Bulk-Materialien oder Einkristallen zielen, muss die Synthese von Nanopartikeln Agglomerate und Ostwald-Wachstum vermeiden. Daher benötigen annehmbare Reaktionszeiten und vergleichsweise tiefe Reaktionstemperaturen kurze Diffusionswege und tiefe Aktivierungsbarrieren. Demzufolge bedient sich die Synthese der Reaktion von Antimon-Nanopartikeln und geeigneten molekularen oder nanopartikulären Edukten der entsprechenden Übergangsmetalle. Zusätzlich wurden anisotrope ZnSb Strukturen synthetisiert, indem eine Templat-Synthese mit Hilfe von anodisierten Aluminiumoxid- oder Polycarbonat-Membranen angewandt wurde. rnDie erhaltenen Produkte wurden hauptsächlich durch Röntgen-Diffraktion und Elektronenmikroskopie untersucht. Die Auswertung der Pulver Röntgendiffraktions-Daten stellte eine Herausforderung dar, da die Nanostrukturierung und die Anwesenheit von mehreren Phasen zu verbreiterten und überlagernden Reflexen führen. Zusätzliche Fe-Mößbauer Messungen wurden im Falle der Fe-Sb Produkte vorgenommen, um detailliertere Informationen über die genaue Zusammensetzung zu erhalten. Die erstmals hergestellte Phase Zn1+xSb wurde einer detaillierten Kristallstrukturanalyse unterzogen, die mit Hilfe einer neuen Diffraktionsmethode, der automatisierten Elektronen Diffraktions Tomographie, durchgeführt wurde.rnrnAus physikalischer Sicht sind Zn4Sb3, ZnSb und FeSb2 interessante thermoelektrische Materialien, die aufgrund ihrer Fähigkeit thermische in elektrische Energie umzuwandeln, großes Interesse geweckt haben. Nanostrukturierte thermoelektrische Materialien zeigen dabei eine höhere Umwandlungseffizienz zu erhöhen, da deren thermische Leitfähigkeit herabgesetzt ist. Da thermoelektrische Bauteile aus dichten Bulk-Materialien gefertigt werden, spielte die Verfestigung der synthetisierten nanopartikulären Pulver eine große Rolle. Die als „Spark Plasma Sintering“ bezeichnete Methode wurde eingesetzt, um die Proben zu pressen. Dies ermöglicht schnelles Heizen und Abkühlen der Probe und kann so das bei klassischen Heißpress-Methoden unvermeidliche Kristallitwachstum verringern. Die optimalen Bedingungen für das Spark Plasma Sintern zu finden, ist Inhalt von bestehender und weiterführender Forschung. rnEin Problem stellt die Stabilität der Proben während des Sinterns dar. Trotz des schnellen Pressens wurde eine teilweise Zersetzung im Falle des Zn1+xSb beobachtet, wie mit Hilfe von Synchrotrondiffraktionsuntersuchungen aufgedeckt wurde. Morphologie und Dichte der verschiedenen verfestigten Materialien wurden mittels Rasterelektronenmikroskopie und Lasermikroskopie bestimmt. Die Gitterdynamik wurde mit Hilfe von Wärmekapazitätsmessungen- und inelastischer Kern-Streuung untersucht. Die Wärmeleitfähigkeit der nanostrukturierten Materialien ist im Vergleich zu den Festkörpern ist drastisch reduziert - im Falle des FeSb2 um mehr als zwei Größenordnungen. Abhängig von der Zusammensetzung und mechanischen Härte wurden für einen Teil der verfestigten Nanomaterialien die thermoelektrische Eigenschaften, wie Seebeck Koeffizient, elektrische und Wärmeleitfähigkeit, gemessen.rn

Metallkomplexe mit sterisch anspruchsvollen mono- und bifunktionellen Triazenidoliganden

Monoanionische, stickstoffhaltige Chelatliganden sind sehr populär und werden oft als Baueinheiten zur Synthese von Metallkomplexen eingesetzt. Im Gegensatz zu den bekannten Amidinat- und β-Diketiminatliganden wurde den Triazeniden bisher weniger Aufmerksamkeit geschenkt. Dies liegt hauptsächlich daran, dass wenige, sterisch anspruchsvolle Vertreter dieser Gruppe bekannt waren. Mit der Synthese neuer biphenyl- und terphenylsubstituierter Triazenide sind diese stärker in den Fokus der Forschung gerückt. Durch die Sperrigkeit der Liganden werden unerwünschte Ligandenumverteilungsreaktionen unterdrückt und der Weg zu neuen Metallkomplexen mit bemerkenswerten Eigenschaften geebnet. Diese Arbeit beschäftigt sich mit Triazenidokomplexen der Alkalimetalle, des Magnesiums, des Zinks und des Aluminiums. Zusätzlich zu den monofunktionellen wurden bifunktionelle Triazene, welche aus einer Biphenylgruppe aufgebaut sind und zwei terphenylsubstituierte Triazengruppen tragen, synthetisiert und deren Funktion als Komplexliganden untersucht. Durch das hohe Volumen der Liganden konnten Metallkomplexe hergestellt werden, die bemerkenswerte strukturelle Eigenschaften aufweisen. So bilden beispielsweise alle dargestellten Verbindungen Kristalle, die aus monomeren Baueinheiten aufgebaut sind. Eine homoleptische Magnesiumverbindung mit zwei Triazenidliganden weist eine ungewöhnliche, planare Koordinationssphäre auf, eine Triazenidodiphenylaluminiumverbindung zeigt eine interessante Ausrichtung der Phenylgruppen, die auf π-Stapeleffekte zurückgeführt wird und die Alkalimetalltriazenide weisen sekundäre Metall-π-Aren-Wechselwirkungen auf, womit eine bessere koordinative Absättigung des Koordinationszentrums erreicht wird. Zusätzlich zur strukturellen Charakterisierung mittels Röntgendiffraktometrie wurden, wo es möglich war 1H und 13C NMR-Messungen durchgeführt, Schmelzpunkte bestimmt sowie IR- und UV-VIS-Spektren aufgenommen. Durch die hohe Dichte an aromatischen Systemen innerhalb der Verbindungen, ist es bei einer dreikernigen Zinktriazenidverbindung gelungen mittels 1H NMR-Messungen die starken Einflüsse des Ringstroms nachzuweisen. Außerdem wurden DFT-Berechnungen durchgeführt, um herauszufinden, wie sehr die räumliche Ausrichtung der Bi- bzw. Terphenylsubstituenten gegenüber der N3-Baugruppe der Triazenide die Verteilung der negativen Ladung innerhalb eines monoanionischen Triazenids und somit dessen Koordinationseigenschaften beeinflusst. Diese Effekte konnten durch experimentelle Ergebnisse unterstützt werden.

Functional characterisation of in vitro synthesised G-protein coupled receptors in polymersomes

Membrane proteins play an indispensable role in physiological processes. It is, therefore, not surprising that many diseases are based on the malfunction of membrane proteins. Hence membrane proteins and especially G-protein coupled receptors(GPCRs)- the largest subfamily- have become an important drug target. Due to their high selectivity and sensitivity membrane proteins are also feasible for the detection of small quantities of substances with biosensors. Despite this widespread interest in GPCRs due to their importance as drug targets and biosensors there is still a lack of knowledge of structure, function and endogenous ligands for quiet a few of the previously identified receptors.rnBottlenecks in over-expression, purification, reconstitution and handling of membrane proteins arise due to their hydrophobic nature. Therefore the production of reasonable amounts of functional membrane proteins for structural and functional studies is still challenging. Also the limited stability of lipid based membrane systems hampers their application as platforms forrnscreening applications and biosensors.rnIn recent years the in vitro protein synthesis became a promising alternative to gain better yields for expression of membrane proteins in bio-mimetic membrane systems. These expression systems are based on cell extracts. Therefore cellular effects on protein expression are reduced. The open nature of the cell-free expression systems easily allows for the adjustment of reactionrnconditions for the protein of interest. The cell-free expression in the presence of bio-mimetic membrane systems allows the direct incorporation of the membrane proteins and therefore skips the time-consuming purification and reconstitution processes. Amphiphilic block-copolymers emerged as promising alternative for the less stable lipid-based membrane systems. They, likernlipids, form membraneous structures in aqueous solutions but exhibit increased mechanical and chemical stability.rnThe aim of this work was the generation of a GPCR-functionalised membrane system by combining both promising alternatives: in vitro synthesis and polymeric membrane systems. This novel platform should be feasible for the characterisation of the incorporated GPCR. Immunodetection of Dopamine receptor 1 and 2 expressed in diblock- and triblock-polymersomes demonstrated the successful in vitro expression of GPCRs in polymeric membranes. Antibodyrnbinding studies suggested a favoured orientation of dopamine receptors in triblockpolymersomes.rnA dopamine-replacement assay on DRD2-functionalised immobilised triblockpolymersomes confirmed functionality of the receptor in the polymersomes. The altered binding curve suggests an effect of the altered hydrophobic environment presented by the polymer membrane on protein activity.

Dendronized ions

In dieser Arbeit wurde die Frage untersucht, inwieweit die divergente Synthese von starren dendritischen Gerüsten genutzt werden kann, um die Eigenschaften von Salzen und Ionen zu verändern und gezielt zu steuern. Motiviert wurde diese Fragestellung durch das Ziel, größere und dadurch schwächer koordinierende Anionen als die bereits in der Literatur beschriebenen Anionen zu erzeugen. In der Tat konnten durch das divergente Wachstum starrer Polyphenylen-Dendronen sterisch sehr anspruchsvolle Borat-Anionen von bislang unerreichter Größe im Nanometerbereich erzeugt werden. Durch die Größe ihrer hydrophoben Hülle und die damit einhergehende sterische Abschirmung der zentralen Ladung weisen starr dendronisierte Ionen eine deutlich verminderte Koordination zu Gegenionen auf. Die Koordinationkraft ließ sich sowohl durch eine stärkere Verzweigung der dendritischen Hülle als auch durch die Perfluorierung der Ionenoberfläche weiter herabsetzen. Schließlich konnten durch den Einbau lichtschaltbarer Funktionen in das starre Dendrimergerüst sogar Anionen mit schaltbarer, veränderlicher Größe und Koordinationskraft hergestellt werden. Darüber hinaus wurde gezeigt, wie sich Gegenionen in Salzen dendronisierter Ionen austauschen lassen, und es wurde eine neue Klasse von Aryl-Triazol-Dendrimeren entwickelt.

Template-assisted patterning of functional polymers

In this thesis, anodic aluminum oxide (AAO) membranes, which provide well-aligned uniform mesoscopic pores with adjustable pore parameters, were fabricated and successfully utilized as templates for the fabrication of functional organic nanowires, nanorods and the respective well-ordered arrays. The template-assisted patterning technique was successfully applied for the realization of different objectives:rnHigh-density and well-ordered arrays of hole-conducting nanorods composed of cross-linked triphenylamine (TPA) and tetraphenylbenzidine (TPD) derivatives on conductive substrates like ITO/glass have been successfully fabricated. By applying a freeze-drying technique to remove the aqueous medium after the wet-chemical etching of the template, aggregation and collapsing of the rods was prevented and macroscopic areas of perfectly freestanding nanorods were feasible. Based on the hole-conducting nanorod arrays and their subsequent embedding into an electron-conducting polymer matrix via spin-coating, a novel routine concept for the fabrication of well-ordered all-organic bulk heterojunction for organic photovoltaic applications was successfully demonstrated. The increased donor/acceptor interface of the fabricated devices resulted in a remarkable increase of the photoluminescence quenching compared to a planar bilayer morphology. Further, the fundamental working principle of the templating approach for the solution-based all-organic photovoltaic device was demonstrated for the first time.rnFurthermore, in order to broaden the applicability of patterned surfaces, which are feasible via the template-based patterning of functional materials, AAO with hierarchically branched pores were fabricated and utilized as templates. By pursuing the common templating process hierarchically polymeric replicas, which show remarkable similarities with interesting biostructures, like the surface of the lotus leaf and the feet of a gecko, were successfully prepared.rnIn contrast to the direct infiltration of organic functional materials, a novel route for the fabrication of functional nanowires via post-modification of reactive nanowires was established. Therefore, reactive nanowires based on cross-linked pentafluorophenylesters were fabricated by utilizing AAO templates. The post-modification with fluorescent dyes was demonstrated. Furthermore, reactive wires were converted into well-dispersed poly(N-isopropylacrylamide) (PNIPAM) hydrogels, which exhibit a thermal-responsive reversible phase transition. The reversible thermal-responsible swelling of the PNIPAM nanowires exhibited a more than 50 % extended length than in the collapsed PNIPAM state. rnLast but not least, the shape-anisotropic pores of AAO were utilized to uniformly align the mesogens of a nematic liquid crystalline elastomer. Liquid crystalline nanowires with a narrow size distribution and uniform orientation of the liquid crystalline material were fabricated. It was shown that during the transition from the nematic to the isotropic phase the rod’s length shortened by roughly 40 percent. As such these liquid crystalline elastomeric nanowires may find application, as wire-shaped nanoactuators in various fields of research, like lab-on-chip systems, micro fluidics and biomimetics.rn