Freigabe: 05.05.2018 Synthesis, characterization and application of smart materials based on low-molecular-weight compounds and polymers

Chapter A: Introduction on supramolecular gels and application of gels in drug release The first section (chapter B1) presents the transfer of a concept which is originally used for the design of new drug molecules, to the rational development of new gelator compounds, namely the isosteric replacement. Here the substitution of the amide function in N stearoyl-L-glutamic acid (C18-Glu) (see Fig. 48) – a compound which is known to be able to act as gelator for several solvents – was replaced by a 1,4-di¬subs¬tituted 1,2,3-triazole unit (click-Glu) and a sulfonamide (sulfo-Glu), respect¬ive¬ly. In both cases the total number of C atoms has formally been kept intact.In terms of gelation of a range of different organic solvents, as well as water, it was found that click-Glu revealed superior features with respect to the CGC, Tgel and mechanical stability in polar protic solvents, whereas sulfo-Glu exhibited improved properties in non-polar solvents and C18-Glu showed in average values between those of click-Glu and sulfo-Glu. But not only the characterization of the gel material itself was described but also the successful application of hydrogels derived from all three glutamic acid derivatives as carriers of several hydrophilic and hydrophobic drugs and the subsequent release over a period up to two weeks could be demonstrated which revealed the influence of the functional group in the respective gelator molecules on the release rate of the drugs. Chapter B2 describes the application of hydrogels, derived from glycyrrhizic acid ammonium salt, as drug depot. Glycyrrhizic acid ammonium salt is a salt of glycyrrhizin, a natural compound which can be extracted from the licorice root. It exhibits an excellent biocompatibility, which is why it was chosen for the formulation and drug release study of three anti-cancer agents of different hydrophilicity. The influence of drug inherent hydrophilicity as well as the pH and nature of the release medium on the drug diffusion rate was investigated. In good agreement with previous publications, more hydrophobic compounds were found to tend to a slower diffusion into the release medium as they experience a greater retention from the gel environment. In terms of pH of surrounding medium, the release into more basic solutions was found to be faster as high pH values seemed to destabilize the integrity of the gel network. However the nature of the release buffer (e.g. organic or inorganic) also played an important role, which makes a forecast of the release kinetics, depending on the pH difficult and therefor demonstrates the limitations of in vitro drug delivery experiments. Nevertheless, preliminary release studies provide important information necessary for the design of in vivo experiments. A formamidine based low molecular weight compound and its gelation properties are presented in chapter B3. The amphiphilic molecule consists of a long chain containing 16 carbon atoms and an acetyl L-phenyl alanine connected via a formamidine group.This molecule is able to form gels in a variety of different organic solvents as well as two ionic liquids and water. It was found that ultrasonication of an isotropic solution of the gelator led to superior materials in comparison to gels prepared by the classical heating and spontaneous cooling of gelator solution. Furthermore temperature controlled 1H-NMR reveled the participation of H-bonding, π - π-stacking, as well as van-der-Waals interactions in the gelation process. Moreover the temperature controlled turning on/off of birefringence of a gel in MeCN could be demonstrated, which constitutes an important property for potential applications in optical devices. Unfortunately this gelator, as well as its hydrogel was found to be toxic, which is why this material could not be used for drug delivery studies. The second half, chapter C of this thesis describes the synthesis of different ionene polymers as well as various applications. In chapter C1 the antimicrobial and hemolytic activity of ionenes (Fig. 51) was investigated. The majority of the polymers showed antimicrobial activity against the Gram-negative bacterium Escherichia coli, with minimum inhibition concentration values affected by both the topology of the polymer and the nature of the diamine linker. Most polymers revealed to be harmless towards red blood cells and therefor show a low hemolytic activity. In general, DABCO containing polymers exhibited the lowest antimicrobial and the highest hemolytic activities. In contrast, meta-ionenes showed the best antimicrobial and lowest hemolytic activity, which makes them promising candidates for potential antimicrobial applications. In chapter C2 cationic vesicles derived from ionene polymers with alternating α,ω-tertiary diamine linker (ortho-DABCO, -C2 and -C6, see Fig. 51) and the non-ionic surfactant polysorbate 80 are presented. These vesicles were used in different formulations for the transfection of oligonucleotide single strands which are comple-mentary to Renilla luciferase mRNA. Formulations based on ortho-DABCO and -C2 were found to be non-toxic but those with ortho-C6 showed critical cell viabilities at higher ionene concentrations. When testing the efficiencies of the cationic vesicles to silence the activity of Renilla luciferase, those formulations with DABCO-ionene showed no efficacy. On the contrast, C2- and C6-ionene derived formulations (at non-toxic ionene concentrations) could reduce the luciferase activity by 48 and 38%, respectively. The use of these formulations might be an interesting alternative to current transfection agents. Last but not least in chapter C3 ionenes with DABCO-linker were found to be able to gel water and acidic solutions. Here the topology, the substitution pattern (ortho-, meta- or para-) at the central benzene of the ionenes, was found to play an highly important role for the gelation properties. Ortho-DABCO showed superior gelation ability compared to the analogues meta-DABCO and para-DABCO in solutions of different pH and ionic strengths. Atomistic MD simulations have allowed to conclude that the distinctive properties of ortho-DABCO are due to the formation of specific polymer ··· polymer interactions (i.e. hydrogen bonds, N–H ··· π and intra-molecular π – π stacking), which are facilitated by the binder effect of Cl- counterions. Polymer ··· polymer interactions are more abundant in ortho-DABCO than in meta-DABCO and para-DABCO which is responsible for the superior gelation of ortho-DABCO

Direct visualization of Rashba-split bands and spin/orbital-charge interconversion at KTaO₃ interfaces

Rashba interfaces have emerged as promising platforms for spin-charge interconversion through the direct and inverse Edelstein effects. Notably, oxide-based two-dimensional electron gases display a large and gate-tunable conversion efficiency, as determined by transport measurements. However, a direct visualization of the Rashba-split bands in oxide two-dimensional electron gases is lacking, which hampers an advanced understanding of their rich spin-orbit physics. Here, we investigate KTaO3 two-dimensional electron gases and evidence their Rashba-split bands using angle resolved photoemission spectroscopy. Fitting the bands with a tight-binding Hamiltonian, we extract the effective Rashba coefficient and bring insight into the complex multiorbital nature of the band structure. Our calculations reveal unconventional spin and orbital textures, showing compensation effects from quasi-degenerate band pairs which strongly depend on in-plane anisotropy. We compute the band-resolved spin and orbital Edelstein effects, and predict interconversion efficiencies exceeding those of other oxide two-dimensional electron gases. Finally, we suggest design rules for Rashba systems to optimize spin-charge interconversion performance

Electronic bandstructure of superconducting KTaO3 (111) interfaces

Two-dimensional electron gases(2DEGs)based on KTaO3 are emerging as a promising platform for spin-orbitronics due to their high Rashba spin-orbit coupling (SOC) and gate-voltage tunability. The recent discovery of a superconducting state in KTaO3 2DEGs now expands their potential towards topological superconductivity. Although the band structure of KTaO3 surfaces of various crystallographic orientations has already been mapped using angle-resolved photoemission spectroscopy(ARPES), this is not the case for superconducting KTaO3 2DEGs. Here, we reveal the electronic structure of superconducting 2DEGs based on KTaO3 (111) single crystals through ARPES measurements. We fit the data with a tight-binding model and compute the associated spin textures to bring insight into the SOC-driven physics of this fascinating system.Comment: 9 pages, 4 figure

Breve, y devota descripcion de la gloriosa celda del padre S. Luis Beltran : acreditada con singulares prodigios, y favores Celestiales ...

ÍndiceSign. : [calderón]4, 2[calderón]3, A1, B-M4Error de sign. está repetida H-H4, entre las p. 59-66Apostillas marginales y ReclamosPort. con orla tip.Letras iniciales decoradas y friso tip.La h. de grab. calc. : "D. Josef Garcia faciebat et esculpit ano 1696", con la imagen de S. Lui

Chemische und analytische Werkzeuge um Protein-Phoshorylationisierung zu studieren

The results presented here from this work showed the power of chemoselective reactions to obtain access towards challenging post-translationally modified peptides. Specifically, two different chemoselective phosphorylation strategies were developed to synthesize site-specifically phosphorylated lysine and cysteine peptides. In addition to solving the synthetic accessibility issue, the site-specifically phosphorylated peptides were used to establish ETD tandem mass spectrometry as a reliable analytical tool to characterize both lysine- and cysteine-phosphorylation sites in a proteomic context.Die Ergebnisse der hier vorgestellten Dissertation zeigen die Leistungsfähigkeit der untersuchten chemoselektiven Reaktionen, vor allem für die Synthese von anspruchsvollen posttranslational modifizierten Peptiden, auf. Im Rahmen der Arbeit wurden zwei unterschiedliche chemoselektive Phosphorylierungsreaktionen, die den Einbau von ortsspezifisch phosphorylierten Lysinen und Cysteinen in Peptiden ermöglichen, entwickelt. Mit Hilfe der synthetisierten Phospholysin und –cystein Peptide konnten ETD- MS/MS Methoden zur zuverlässigen analytischen Charakterisierung solcher Peptid- und Proteinmodifizierung entwickelt werden

Estudios de tipologia linguistica

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai