Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 04/06 Archiv

Optical microscopy is widely used to visualize small structures that can not be seen by the unaided human eye. On the nanoscale, however, the diffraction limit prevents conventional microscopy from studying materials with the required spatial resolution. This work reports on tip-enhanced near-field optical microscopy (TENOM), a technique that allows for nanoscale optical imaging with high detection sensitivity. It exploits the locally enhanced optical fields at a laser illuminated metal tip that acts as an optical antenna. The main aims of this work are to develop a better understanding of the signal enhancement mechanisms in TENOM and to apply the technique to different 1D semiconducting nanostructures, namely single-walled carbon nanotubes (SWCNTs) and cadmium selenide nanowires (CdSe NWs). In the first part, the angular distribution of photoluminescence (PL) emission from SWCNTs with and without the optical antenna is studied by imaging the back focal plane of the microscope objective. Using model calculations, it is shown that the PL of SWCNTs on a dielectric substrate can be described as emission from a single in-plane point dipole despite the quasi 1D structure of the nanotubes. The signal enhancement due to the antenna is connected to a substantial redistribution of the angular emission. A procedure for the individual quantification of the excitation and radiation rate enhancement factors is developed and applied to the experimental data. In the second part, nanoscale optical imaging of CdSe NWs using TENOM is presented for the first time. Spectrally resolved imaging reveals different band gaps for different NWs and variations of the PL energy and intensity along single NWs with energy gradients up to 1 meV/nm. Even bundled NWs can be spatially resolved by their PL and Raman signals. The third part reports on the angular and spectral emission properties of CdSe NWs and the tip-induced changes in a TENOM measurement. In contrast to SWCNTs, two perpendicularly oriented point dipoles are required to describe the angular intensity distribution of PL emission from CdSe NWs sufficiently. Again, tip-induced signal enhancement is accompanied by a spatial redistribution of the emission. The theoretical description is more complex than in the case of SWCNTs, because different radiating dipole orientations in the NW have to be taken into account that can interact with the tip. Finally, investigations of the tip-sample distance dependence of PL and Raman scattering are presented and discussed.

In this thesis various possibilities to employ s-triazine and s-heptazine compounds as building blocks in novel materials are presented. Different molecular s-triazine and s-heptazine derivatives have been utilized as building units in molecular salts, coordination and supramolecular compounds. Special attention has been paid to increased employment of s-heptazine derivatives and of molecules which can be classified as intermediates between inorganic carbon nitride type compounds and hydrocarbons. In the obtained materials different types of interactions except for covalent bonds determine specific assemblies of components in the crystal. Detailed analysis of impact and mutual influence of diverse types of noncovalent forces on the arrangement of molecular entities has been performed in order to gain a deeper understanding of these interactions, which will hopefully facilitate more directed syntheses of such materials in the future. Structural characterization has been complemented by analysis of chemical and thermal stability, and thereby the suitability of investigated compounds to be employed as building blocks in novel materials could be evaluated.

Insights into the developmental processes during which the brain forms from the neuroepithelium may provide a deeper understanding how the brain works. The Rho family of small GTPases is known for its many cell biological functions such as regulation of the cytoskeleton, gene expression, cell migration, adhesion, cell polarity and the cell cycle. All of these functions are of importance during the formation of the cerebral neocortex, which consists of the generation of its different cell types, their migration to their destination and their maturation to a functional network. These roles have been mostly established in vitro using dominant negative or constitutively active constructs. Since these approaches are often not entirely specific for single pathways, this work used the Cre/loxP system to genetically delete an individual member of the Rho family, RhoA, to examine its role following a loss-of-function approach. Specifically, we examined a mouse line where part of the RhoA gene has been deleted by means of the Emx1::Cre mouse line. This idea is based on previous experiences with the deletion of Cdc42 in the developing neocortex, which leads to a loss of apical progenitors. RhoA often works as a functional antagonist to Cdc42. Using immunofluorescence, we could detect a loss of RhoA at embryonic day 12 (E12) in Emx1::Cre-positive offspring carrying the floxed RhoA-construct in both alleles (cKO). At E14, we detected an increase in mitotic cells to 160% (±25%, p

Mit der Cholesterolbiosynthese sind verschiedenste Krankheiten assoziiert, wie beispielsweise Hypercholesterinämie oder auch neurodegenerative Krankheiten wie Morbus Alzheimer oder die Creutzfeldt-Jakob-Krankheit. Andererseits werden durch die kontinuierlich steigende Anzahl immun supprimierter Patienten Infektionen mit opportunistischen Pilzen ein schwerwiegendes Problem steigender Bedeutung. Da sich die Enzyme der Cholesterol- und der Ergosterolbiosynthese unterscheiden, ist es möglich, in diese selektiv einzugreifen. Durch Inhibition einzelner Enzyme der Cholesterolbiosynthese ergeben sich Möglichkeiten zur Senkung des Serumcholesterolspiegels und damit zur Behandlung der Hypercholesterinämie oder auch Ansätze zur Behandlung oder gezielteren Untersuchung von anderen Cholesterolbiosynthese-assoziierten Erkrankungen. Die selektive Hemmung von Enzymen der Ergosterolbiosynthese kann zur Behandlung von Erkrankungen durch schädliche Pilze oder Protozoen genutzt werden. Im Rahmen dieser Arbeit gelang es diverse Modifikationen in der Seitenkette von Steroidderivaten ausgehend von Ergosterol durchzuführen und so beispielsweise Gruppen mit potenzieller Reaktivität gegenüber Thiolen, metallchelatisierende Gruppen oder auch Ester und Amide einzuführen. Unterschiedlichste Strukturen ließen sich in arbeitskreisinternen Assays als potente selektive Inhibitoren verschiedener Enzyme der Ergosterol- oder Cholesterolbiosynthese klassifizieren.

The objective of the thesis was the lyophilization of cationic polymer-based pDNA or siRNA nanoparticles (i.e. polyplexes) with a special focus on the development of long-term stable formulations, the investigation of stabilization mechanisms especially during freezing, and the advanced monitoring of the lyophilization process. It was shown that an up-scaled preparation method in combination with subsequent lyophilization is a promising approach to reproducibly achieve long-term stable pDNA or siRNA polyplexes maintaining particle size and biological activity at pharmaceutically defined high quality. The results demonstrated that formulation development, highly dependent on the used type of polymer or nucleic acid, and process development, with a strong focus on the freezing, in combination with appropriate process monitoring needs always to be performed hand in hand. All in all, this thesis makes an essential contribution in order to move closer from a promising biotechnological approach towards clinic-friendly drugs.