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1	Development and Validation of Methods for Characterization of Multi-Component Systems in Preparative LC / Utveckling och Validering av Metoder för Karaktärisering av Flerkomponentsystem vid Preparativ Vätskekromatografi Arnell, Robert January 2006 (has links) <p>This thesis concerns the development and validation of methods for characterization of multi-component preparative LC systems. Measurements of competitive adsorption isotherms are performed to gain detailed information about the interactions inside the chromatography column. This information increases our understanding of the separation process and makes it possible to perform computer simulations and numerical optimizations to find optimal operating conditions.</p><p>The methods under focus are called “the tracer-pulse method”, “the inverse method”, and “the inverse method on plateaus”. They are extensions of existing methods, with new experimental and numerical procedures to enable rapid and accurate multi-component adsorption isotherm determination. In the validation it was shown that they can produce results agreeing with traditional methods and that the acquired adsorption isotherm parameters can be used in simulations to accurately predict the outcome of preparative LC separations.</p><p>The methods were used to characterize several complex LC systems and two phenomena were discovered and theoretically treated: 1) The presence of invisible deformed peaks in single-component systems. 2) Peak deformations encountered with modern chiral stationary phases, caused by strongly adsorbed eluent additives. The latter type of deformation was highly tuneable and it was possible to adjust the enantiomer peak shapes so that the peaks tailed in opposite directions with the sharp sides in between, yielding baseline resolution at remarkably high sample loads.</p><p>In a final applied study both the LC-based perturbation peak method and a biosensor method based on surface plasmon resonance (SPR) were used for the first time for detailed characterization of chiral drug-protein interactions. The fundamental properties of the two very different methods were compared and it was found that the LC method is more suitable for multi-component analysis and that the SPR method is more suitable for stronger interactions.</p> Analytical chemistry Liquid chromatography Preparative LC Chiral LC Multi-component LC Adsorption isotherm Tracer-pulse method Inverse method Inverse method on plateaus Peak deformations Chiral drug-protein interactions Analytisk kemi
2	Development and Validation of Methods for Characterization of Multi-Component Systems in Preparative LC / Utveckling och Validering av Metoder för Karaktärisering av Flerkomponentsystem vid Preparativ Vätskekromatografi Arnell, Robert January 2006 (has links) This thesis concerns the development and validation of methods for characterization of multi-component preparative LC systems. Measurements of competitive adsorption isotherms are performed to gain detailed information about the interactions inside the chromatography column. This information increases our understanding of the separation process and makes it possible to perform computer simulations and numerical optimizations to find optimal operating conditions. The methods under focus are called “the tracer-pulse method”, “the inverse method”, and “the inverse method on plateaus”. They are extensions of existing methods, with new experimental and numerical procedures to enable rapid and accurate multi-component adsorption isotherm determination. In the validation it was shown that they can produce results agreeing with traditional methods and that the acquired adsorption isotherm parameters can be used in simulations to accurately predict the outcome of preparative LC separations. The methods were used to characterize several complex LC systems and two phenomena were discovered and theoretically treated: 1) The presence of invisible deformed peaks in single-component systems. 2) Peak deformations encountered with modern chiral stationary phases, caused by strongly adsorbed eluent additives. The latter type of deformation was highly tuneable and it was possible to adjust the enantiomer peak shapes so that the peaks tailed in opposite directions with the sharp sides in between, yielding baseline resolution at remarkably high sample loads. In a final applied study both the LC-based perturbation peak method and a biosensor method based on surface plasmon resonance (SPR) were used for the first time for detailed characterization of chiral drug-protein interactions. The fundamental properties of the two very different methods were compared and it was found that the LC method is more suitable for multi-component analysis and that the SPR method is more suitable for stronger interactions. Analytical chemistry Liquid chromatography Preparative LC Chiral LC Multi-component LC Adsorption isotherm Tracer-pulse method Inverse method Inverse method on plateaus Peak deformations Chiral drug-protein interactions Analytisk kemi
3	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. Alzheimer's disease neurodegenerative disorders protein aggregates molecular ligands amyloid-β Aβ amyloid-beta tau diagnosis HS-259 staining brain tissue Suzuki coupling Ullmann arylation condensation NMR nuclear magnetic resonance LC-MS liquid chromatography neuropathological hallmarks absorption spectra emission spectra synthesis plaques symptoms neuropathology thiophene-vinyl-benzothiazole TVBT ligand analogues N-arylation Knoevenagel preparative LC PBS phosphate buffered saline treatments AD mechanisms thiophene benzothiazolium fluorescence imaging bTVBT bi-thiophene-vinyl-benzothiazole detection Suzuki-Miyara Organic Chemistry Organisk kemi

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