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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Synthesis of Thiophene-Vinyl-Benzothiazole Based Ligand Analogues for Detection of Aβ and Tau Pathology in Alzheimer's Disease

Johansson, Joel January 2024 (has links)
As of today, Alzheimer’s disease is the leading cause of dementia among neurodegenerative disorders, affecting many millions of people worldwide. As the average life span of populations increase, more and more people succumb to the illness each year. Like other neurodegenerative disorders, Alzheimer’s disease can be attributed to the accumulation of protein aggregates in the brain. These amyloid-β peptides and tau proteins can presumably be detected in the brain many years before the onset of clinical symptoms. Development of fluorescent ligands, capable of binding to these neuropathological hallmarks and highlighting them, could serve as molecular diagnostic tools and facilitate an early diagnosis of the disease. The method could also be useful in studying disease progression and evaluating the effects of novel treatments. One such ligand is HS-259. The aim of this project was to synthetize different analogues of HS-259, and test their selectivity towards the aforementioned aggregates in brain tissue from an individual with Alzheimer’s disease. Staining of tissue samples with analogue solution enables visualization of aggregate sites through fluorescence imaging. In the end, five analogues were synthetized, albeit in relatively low overall yields. Synthetic methods included Suzuki-Miyara cross-couplings, Ullmann-type arylations and condensations. Liquid Chromatography-Mass Spectrometry (LC-MS) and Nuclear Magnetic Resonance (NMR) were used for analysis of the compounds. Two of the five analogues could be tested for staining of aggregates and assessed for photophysical characteristics, i.e. absorption- and emission spectra. One analogue stained both amyloid-β aggregates and some tau aggregates, whereas the other stained neither. Since only two analogues were tested and rendered inconsistent results, further studies are needed to assess the binding properties of HS-259 analogues in general.
32

Synthese neuer tri- und hexadentater Stickstoffbasen für Eisen(II) Spin Crossover Komplexe

Heider, Silvio 20 August 2013 (has links)
Die vorliegende Arbeit thematisiert Eisen(II)-Komplexe mit Spinübergangseigenschaften. Dafür wurden neue hexadentate Liganden auf Basis von N,N'-Bis(2,2'-bipyridin-6-ylmethyl)-2,2'-biphenylendiamin entwickelt. Die in Kapitel 3.1 vorgestellten Systeme variieren dabei in den jeweiligen Substituenten der 6,6‘-Positionen der Biphenyleinheit. Es wird der Einfluss dieser Gruppen auf die magnetischen Eigenschaften der resultierenden Komplexe gezeigt. Im darauffolgenden Kapitel 3.2 wird ein variiertes Ligandensystem vorgestellt, in welchem anstelle einfacher Substituenten Donorfunktionen eingeführt wurden, sodass ein symmetrischer dinuklearer Eisen(II)-Komplex zugänglich war. In diesem sind die beiden Spin Crossover (SCO) Zentren erstmalig durch eine Biphenyleinheit verbrückt. Die durchgeführten Untersuchungen geben Hinweise auf eine allostere Wechselwirkung. Weiterhin wurde der Ligand durch N-Methylierung in ein tertiäres Amin überführt und die entsprechenden Komplexe mit Fe(II), Co(II) und Zn(II) synthetisiert (Kapitel 3.3). Diese wurden strukturell und elektrochemisch untersucht und hinsichtlich ihrer Redoxeigenschaften und Magnetismus mit den Komplexen der sekundären Amine verglichen. Ebenfalls wurde das Grundgerüst des auf sekundären Aminen basierenden Liganden so variiert, dass der terminale Donor durch stickstoffhaltige Fünfringheterocyclen – anstelle von Pyridin – verkörpert wurde (Kapitel 3.4). So konnten Eisen(II)-SCO Komplexe erhalten werden, welche eine wesentlich niedrigere Übergangstemperatur aufwiesen und somit magnetische Untersuchungen im Festkörper sowie des Photomagnetismus ermöglichten. Schließlich wurden neue tridentate Amine (2-(6-R-Pyridin-2-yl)-1,10-phenanthrolin) und deren Eisen(II)-Komplexe synthetisiert (Kapitel 3.5). Für einige dieser Komplexe konnte bereits das Spin Crossover Verhalten in Lösung untersucht werden. / The present thesis addresses iron(II) complexes with spin transition properties. For this purpose new hexadentate ligands were developed on the basis of N,N’-bis(2,2’-bipyridine-6-ylmethyl)-2,2’-biphenylenediamine. The systems introduced in chapter 3.1 vary in respect to the substituents in the 6,6’-positions of the biphenyl unit. The influence of these varying moieties on the magnetic behavior of the resulting complexes is shown. In the following chapter 3.2 a tuned ligand system is introduced, in which the substituents are donor functions so that a symmetrical dinuclear iron(II) complex was feasible. In this the two Spin Crossover (SCO) centers are for the first time connected by a biphenyl core. The executed experiments give hints to an allosteric interaction in this dinuclear compound. Moreover the ligand was reacted by N-methylation yielding a tertiary amine and the corresponding complexes with Fe(II), Co(II) and Zn(II) were synthesized (chapter 3.3). Those were investigated structurally and electrochemically and were then compared with the complexes with secondary amines in respect to their redox and magnetic properties. The ligand motif based on secondary amines was also modified in a way that the terminal donor was represented by nitrogen based five-ring heterocycles instead of pyridine (chapter 3.4). So iron(II) SCO complexes were available which showed much lower thermal transition temperatures and thus magnetic investigations in the solid state as well as investigations on the photomagnetic properties became possible. Ultimately, novel tridentate amines (2-(6-R-pyridine-2-yl)-1,10-phenanthroline) and the corresponding iron(II) complexes were synthesized (chapter 3.5). For some of those complexes the spin transition could already be monitored in solution.

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