Synthesis and Characterization of Sequence-Defined Stiff Oligomers Using the Sonogashira Reaction

Konjugierte Stäbchenmoleküle sind interessante Verbindungen für elektronische Anwendungen. Mehrere iterative Syntheseverfahren zu monodispersen Phenylalkin-Oligomeren wurden publiziert, aber nur ein Beispiel zu derartigen sequenzdefinierten Oligomeren existiert. Dabei könnten sequenzdefinierte, konjugierte Oligomere einen wichtigen Beitrag zur Erforschung von Struktur-Eigenschafts-Beziehungen liefern. In dieser Arbeit wird ein lineares Syntheseverfahren zu sequenzdefinierten Phenylalkin-Oligomeren in Lösung vorgestellt. Dafür wurden verschiedene Bausteinmoleküle mit einem Halogen und einer geschützten Dreifachbindung synthetisiert. Verschiedene Dialkyloxysubstituenten zur besseren Löslichkeit weisen zusätzlich elektronenschiebende Eigenschaften auf. Des Weiteren wurden Elektronenakzeptor-Bausteine hergestellt. Die Stäbchenmoleküle wurden über Zyklen von Sonogashira Kreuzkupplung und anschließender Entschützung der Dreifachbindung realisiert. Zunächst wurde Phenylacetylen als Starteinheit mit einem Bausteinmolekül umgesetzt und das entsprechende Monomer erhalten. Mit dem vorgestellten Syntheseverfahren konnten ein monodisperses und ein sequenzdefiniertes Pentamer in jeweils zehn Reaktionsschritten erhalten werden. Die Ausbeute für das monodisperse Pentamer belief sich dabei auf 18% und 116 Milligramm. Für das sequenzdefinierte Pentamer wurde eine Ausbeute von 3.2% und 73.6 Milligramm erhalten. Die finalen Produkte sowie die entsprechenden Intermediate wurden vollständig mit 1H und 13C-NMR, IR-Spektroskopie und Massenspektrometrie charakterisiert. Zusätzlich wurde SEC und DSC durchgeführt und die photophysikalischen Eigenschaften mit UV/Vis-Spektroskopie untersucht. Ein direkter Oligomerisierungsversuch zu monodispersen Stäbchenmolekülen mit einem Kettenstopper führte zu einem Gemisch aus vielen Oligomeren und rechtfertigt die iterative Reaktionsführung. In dieser Arbeit wurden außerdem Stäbchenmoleküle mit Farbstoffen, die eine thermisch aktivierte verzögerte Fluoreszenz aufweisen, mittels Sonogashira Reaktion verknüpft und vollständig charakterisiert. Mit diesen Verbindungen könnten optoelektronische Vorgänge in organischen Solarzellen untersucht werden

A Direct One-Pot Modification of β-Cyclodextrin via the Ugi-Five-Component Reaction

Starch‐derived β‐cyclodextrins (β‐CDs) are used in pharmacy or the food and cosmetic industry as drug deliverers, separating agents, catalysts, detergents, or viscosity modifiers. However, solubility issues often restrict their potential applications. Here, we report a straightforward and direct one‐pot synthesis for the modification of β‐CDs based on the Ugi‐five‐component reaction (Ugi‐5CR). The Ugi‐5CR requires to react an amine, an aldehyde, an isocyanide, carbon dioxide and the β‐CD, which serves as alcohol component. Overall, five modified β‐CDs containing carbamate moieties were synthesized at room temperature in a high pressure reactor (10 bar) within 24 hours. The successful modifications are verified by mass spectrometry, nuclear magnetic resonance, and infrared spectroscopy, indicating one to three reacted primary hydroxyl groups per β‐CD. Additionally, we report altered solubility behavior of two of the five modified β‐CDs

Role of Genetic Haploinsufficiency in the Biology and Targeted Therapy of Del(5q) Myelodysplastic Syndrome

The studies presented in this thesis focused on the identification of genes that play a central role in the pathogenesis of myelodysplastic syndromes with a deletion of the short arm (q) of chromosome 5, the del(5q) MDS. The overall goal of the projects was to gain a better understanding of how gene haploinsufficiency in (del)5q MDS leads to a clonal advantage, ineffective hematopoiesis and how haploinsufficiency can be targeted. Heterozygous deletion of RPS14 occurs in del(5q) myelodysplastic syndrome (MDS) and has been linked to impaired erythropoiesis, characteristic of this disease subtype. So far, it was not well understood how ribosomal haploinsufficiency affects protein synthesis and if differentially translated proteins have a impact on the erythroid differentiation defect (chapter 1). We generated a murine model with conditional inactivation of Rps14 and demonstrated a p53-dependent erythroid differentiation defect with apoptosis at the transition from polychromatic to orthochromatic erythroblasts resulting in age- and erythroid stress dependent progressive anemia, megakaryocyte dysplasia, and loss of hematopoietic stem cell (HSC) quiescence (chapter 2). Protein synthesis was significantly reduced in Rps14 haploinsufficient hematopoietic stem cells and in particular in erythroid progenitor cells relative to wild-type cells. As assessed by quantitative proteomics, Rps14 haploinsufficient erythroblasts expressed higher levels of proteins involved in innate immune signaling, notably the heterodimeric S100 calcium-binding proteins S100a8 and S100a9 (alarmins). S100a8 is functionally involved in the erythroid defect caused by the Rps14 deletion, as addition of recombinant S100a8 was sufficient to induce an erythroid differentiation defect in wild-type erythroid cells (phenocopy), and genetic inactivation of S100a8 expression rescued the erythroid differentiation defect of Rps14-haploIn the current study it was our goal to focus on important design criteria including (1) the opportunity for reproducible and user-defined properties such as the choice of substrate, extracellular matrix, cell types, and degradability; (2) the ability to induce vascularisation; (3) accessibility and suitability for complementary histological/cytological analysis; and, most importantly, (4) the functional ability to capture and retrieve endogenous hematopoietic cells efficiently

A Practical and Efficient Synthesis of Uniform Conjugated Rod‐Like Oligomers

Herein, a more practical and efficient synthesis protocol for the preparation of uniform rod-like oligo(1,4-phenylene ethynylene)s (OPE)s is presented. Applying an iterative reaction cycle consisting of a decarboxylative coupling reaction and a saponification of an alkynyl carboxylic ester, a uniform pentamer is obtained in ten steps with 14% overall yield. The copper-free conditions prevent homocoupling until the trimer stage, resulting in a significantly easier work-up of the products. Homocoupling is observed from the tetramer stage on, but a simple variation of the work-up procedure also yields the uniform tetramer and pentamer. A thorough comparison with the commonly used and described Sonogashira approach reveals that with the new presented strategy, OPEs can be built in similar overall yield, but easier purification and in a quarter of the time. All oligomers are fully characterized by proton and carbon nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS), size-exclusion chromatography (SEC), and infrared spectroscopy (IR)

Puzzling pieces of chromosome 7 loss or deletion

In this issue of Blood, Inaba et al review the challenges and questions to be answered in the molecular and functional dissection of loss of chromosome 7 (monosomy 7 [-7]) and deletion of a segment of the long arm (del(7q)) found in patients with various syndromes involving the myeloid blood cell lineage

Research of spectral and luminescent properties of humic acids of various genesis

The spectral-luminescent properties isolated by means of aqueous-alkaline extraction humic acids of various origin have been studied. A comparative analysis of humic acids obtained from brown coal with "Fluka" humic acids standard sample was carried out. It is shown that the obtained samples of humic acids have their own unique properties and differences due to the complexity of their structure