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Carborane Derivatives for Nuclide Therapy and Imaging : Synthesis and Radio-labellingWinberg, Karl Johan January 2003 (has links)
This thesis describes synthesis and radiohalogenation of closo-carborane and nido-carborate derivatives for application in nuclide therapy and imaging. The work could be divided in to four sections. In the first section, the synthesis of three boronated DNA-intercalators – 1–(N-9-acridinyl-3-aminopropyl)-para-carborane-12-carboxylic acid hydrogen chloride, 1-[1-(N-9-acridinyl-3-aminopropyl)-para-carborane 12-(3-propyloxi)]-1,3-propanediol, 1-(N-9-acridinyl-3-amino-propyl)-1-ortho-carborane-2-ylmethoxy)1-3-propandiol – for potential use in BNCT, using targeted delivery is described. The second section describes the application of the Heck-reaction to 2-iodo-para-carborane, which has successfully been reacted with a number of styrene derivatives, i.e. para-phenyl, chloro, bromo, nitro, methoxy, and methyl-styrene, to furnish the desired trans-β-2-B-para-carborane)styrene. In the third section, radio-iodination and radio-bromination of closo-carboranes is described. Reaction of the corresponding iodinated carborane, in the presence of palladium catalyst, [125I]iodinated and [76Br]brominated carboranes were obtained in high to excellent yields. Section four describes a method for indirect radiolabelling of antibodies with 76Br. It was shown that NBI, a isothiocyanatobenzene derivative of dodecahydro-7,8-dicarba-nido-undecaborate anion, could be radio-brominated using oxidative conditions. The radio-brominated NBI was thereafter conjugated to anti-HER2 antibody for biological evaluation.
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Non-ionic block copolymers and proteins at the air-water interfaceRippner Blomqvist, Brita January 2005 (has links)
The behavior of block copolymer and protein films at interfaces is of central importance to their function in many application areas. Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers function e.g. as emulsifiers and in coatings in oral, parenteral, and topical pharmaceutical formulations and are also widely used for cleaning purposes. The globular protein β-lactoglobulin is the most abundant whey protein and it is used within the food industry as a component of many common foods. To understand the interfacial behavior of block copolymers and proteins in such applications one has to study molecular processes like adsorption, the responses to shear and dilatational deformation of the interface (i.e. surface rheology), conformational changes of the molecules, and forces that are generated between interfacial layers. Such investigations form the focus of the work presented in this thesis. Thin film measurements with a series of block copolymers composed of poly(ethylene oxide) and poly(butylene oxide) revealed that the thickness of foam films (air-aqueous solution-air) is determined by electrostatic and steric repulsion. The range of the steric repulsion is directly dependent on the size of the polymer, in particular the length of the poly(ethylene oxide) chains. Block copolymers attached to the air-water interface change their conformation with increasing surface concentration. The study of the dilatational modulus as a function of the surface pressure of spread and adsorbed block copolymer layers showed that the block copolymers pass from a two-dimensional conformation to a three-dimensional extended structure as the available area per molecule decreases. Relaxation processes occur mainly by a redistribution of segments within the surface layer. Mixing of the hydrophobic poly(propylene oxide) segments in a sublayer of poly(ethylene oxide) and water was proposed to occur at high surface concentration of the polymer. Conformational changes (partial denaturation) of globular proteins upon adsorption at the air-water interface leads to the formation of highly viscoelastic networks, which play an important role for the stabilization of foams and emulsions. Mixed layers, formed by competitive adsorption of β-lactoglobulin and block copolymers, were also investigated. On increasing the concentration of block copolymer, the viscoelasticity of the mixed protein/block copolymer layer gradually decreased. The polymer was able to displace the protein from the interface. The drainage rate of thin liquid films was also enhanced by the presence of block copolymer. Whether or not the incorporation of the polymer in the β-lactoglobulin layer has a detrimental effect on foam stability depends on the ability of the polymer to generate long-range steric repulsion across the foam films. For pure block copolymer systems, correlations between foam stability and the thickness of interfacial layers, in the steric regime, were found. The results obtained can be utilized for increasing the understanding of the mechanisms for foam stabilization in both model and industrial systems. / QC 20101011
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Macrocyclic polypeptides from plantsGöransson, Ulf January 2002 (has links)
The aim of this work was to explore the structural and functional diversity of polypeptides that are found in plants. Expanding knowledge of simililarities between plant use of these compound and animal use promises exceptional opportunities for finding, from plant research, new structures with biomedical and biotechnological potential. A fractionation protocol was developed and applied to many plant species, providing fractions enriched in polypeptides, amenable to chemical and biological evaluation. From one species, the common field pansy (Viola arvensis), a 29-amino-acid residue polypeptide was isolated, named varv A, which revealed a remarkable macrocyclic structure (i.e., N- and C-termini are joined) stabilised by three knotted disulfides. Varv A, together with an increasing number of homologous peptides, form the currently known peptide family of cyclotides. Their stable structure makes them an attractive scaffold for protein engineering. In addition, they display a wide range of biological activities (e.g., antimicrobial, cytotoxic, and insecticidal). As a part of this work, the cytotoxic effects of varv A and two other isolated cyclotides were evaluated in a human cell-line panel: all were active in the low µM range. Most likely, these effects involve pore formation through cell membranes. Cyclotides were found to be common in the plant family Violaceae; with eleven cyclotides isolated and sequenced from V. arvensis, V. cotyledon, and Hybanthus parviflorus. For six members of the genus Viola, cyclotide expression profiles were examined by liquid chromatography-mass spectrometry (LC-MS): all expressed notably complex mixtures, with single species containing more than 50 cyclotides. These profiles reflect the evolution of the genus. To assess these mixtures, a rational strategy for MS based amino acid sequencing of cyclotides was developed, circumventing inherent structural problems, such as low content of positively charged amino acids and the macrocyclic structure. This was achieved by aminoethylation of cysteines, which, following tryptic digestion, produced fragments of size and charge amenable to MS analysis. This method was also modified and used for mapping of disulfide bonds. Methods for isolation and characterisation developed in this work may prove useful not only for further studies on macrocyclic polypeptides from plants, but also for other plant peptides and disulfide-rich peptides from animals.
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Development of Techniques and Methods for the Quantitative Analysis of Endogenous Substances by Microcolumn Liquid Chromatography Coupled to Mass Spectrometry / Utveckling av tekniker och metoder för kvantitativ analys av endogena substanser med mikrokolonn vätskekromatografi sammankopplad med masspektrometriAmirkhani, Ardeshir January 2004 (has links)
Liquid chromatography-mass spectrometry (LC-MS) is a powerful technique for the analysis of endogenous compounds. The introduction of electrospray ionization (ESI) as an interface between LC and MS has contributed strongly to a trend towards miniaturization of LC, due to the possibility to perform ESI at low flow rates. In this thesis, several aspects regarding the design of miniaturized LC systems and electrospray emitters were investigated. In addition miniaturized LC-ESI-MS have been used for the qualitative and quantitative analysis of endogenous polar compounds, peptides and protein digests. The performance of miniaturized LC-MS was compared using different electrospray emitter configurations. The results indicated that the efficiency of the LC system is rather independent of the configuration of the emitter. The lifetime of gold-coated fused silica electrospray emitters based on vapor deposited adhesion layers of titanium were investigated. The long lifetime of the emitter facilitates the use in LC-MS experiments, exemplified LC-MS by analysis of neuropeptides. The ESI voltage is shown to interfere with liquid chromatographic separations performed in packed porous graphitic carbon capillary column. This interference is ascribed to the presence of an electric field over the conductive column in absence of a ground point between the column and the ESI emitter. The solid supported enhanced microdialysis for analysis of neuropeptides were compared with conventional microdialysis. The difference between the two methodologies were evaluated by LC-MS analysis of the microdialysates. The solid supported method gave in general higher relative recoveries. Finally, a method of standard addition was developed to determine total level of tryptophan and two of its metabolites in human plasma by capillary LC-ESI tandem mass spectrometry. The method was applied in a clinical study of multiple scleroses patients treated with cytokines (IFN Beta 1a, 1b). The results show that the intervention effects the tryptophan metabolism.
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Coupled Liquid Separation and Spectrometric Detection of Organic Compounds Containing Hetero-atomsNilsson, Eva January 2004 (has links)
This thesis exemplifies the strength in the combination of inductively coupled plasma (ICP) spectrometry and electrospray ionization tandem mass spectrometry ESI-MS/MS as detection techniques for liquid chromatography (LC) in the search for and investigation of compounds that bind or can bind hetero-atoms. Furthermore, some aspects involved in the coupling of LC and ICP spectrometry and quantification without identical standards have been studied. The importance of using a separation step in combination with ICP spectrometry was shown for urine and blood plasma samples from patients treated with boron neutron capture therapy. In addition to the carrier molecule used in the therapy, one major and a few possible minor metabolites were found in the urine samples. One fragment mass of the major metabolite was obtained with LC-ESI-MS/MS. Liquid chromatography coupled to ICP-MS was also shown to be a valuable tool for fingerprinting metal-binding compounds in complex matrices, such as siderophores (iron-complexing compounds) in soil. The presence of at least two siderophores in a field soil solution sample could be revealed by LC-ICP-MS. Their identities could thereafter be determined by LC-ESI-MS/MS. The non-UV-absorbing o-carboranylalanine could be quantified in relation to its degradation products by LC-ICP-AES, which provided information about the mechanism behind the degradation. Moreover, LC-ICP spectrometry was shown to provide an accurate quantification of biomolecules (bias < 10 %) when evaluated from external calibration graphs based on inorganic elemental standards. Finally, the causes of the large decrease in boron signal seen when adding acetonitrile to the LC mobile phase in LC-ICP-MS was investigated in some detail. Space charge effects might explain a large part of the depression from carbon species on the boron signal.
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Datorstött lärande på gymnasieskolan inom naturvetenskapliga ämnen : med speciell betoning på kemididaktiken.Bjarnason, Bjarni January 2006 (has links)
Elever upplever allt som oftast svårigheter med den naturvetenskapliga undervisningen som ofta upplevs som abstrakt och overklig. De förklaringsmodeller som har beskrivits kring detta är att eleverna har svårigheter med att växla mellan makro (det man ser med ögat) och mikro (molekylär värld). I flera publikationer har man kunnat visa att för att nå en bred publik bör man aktivera så många sinnen som möjligt vilket är det som jag tar fasta på i detta arbete. Datormedierad multimedia framställning i undervisningen har, i publikationer, visat sig kunna kan skapa en bättre förståelse hos elever i kemi. Framförallt är det datorgenererad media framställning som simultant kan presenterar kemiska förlopp med olika representationer som har visat sig ge bra resultat. I denna studie har man kunnat visa att elever är mycket positiva till denna typ av framställning där man kan utföra experiment och se animeringar. De menar också själva att detta underlättar förståelsen av den molekylära världen. Genom att studera fall och kontroll kunde man även i denna studie visa på vissa skillnader i elevers kunskaper. De elever som fick möjlighet att studera animeringar och göra virtuella laborationer hade något bättre resultat än de som inte fick denna möjlighet.
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Fortsatta studier i kemi : Orsaker bakom gymnasieelevers val för framtiden / Further Studies in Chemistry : Causes of secondary school students' choices for the futureLjung, Ida January 2010 (has links)
Syftet med denna studie var att se närmare på gymnasieelevers vilja och lust för fortsatta studier i kemi. Studien genomfördes med kvalitativa intervjuer av tio gymnasieelever på det naturvetenskapliga programmet på en mindre ort i Sverige. Resultatet visade på att alla dessa elever ville läsa vidare efter gymnasiet, men enbart två kunde tänka sig en kemiutbildning. Övriga elever hade antingen redan bestämt sig för någon annan utbildning eller blivit avskräckta från att läsa kemi på grund av sättet undervisningen var upplagd i skolan. De elever som möjligen skulle vilja läsa vidare inom kemiområdet kände, liksom flera av de andra eleverna, att skolan inte givit tillräcklig information kring möjliga yrken inom de olika naturvetenskapliga områdena.
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Pulse propagation in photonic crystals and nonlinear mediaKimberg, Victor January 2005 (has links)
<p>The present thesis is devoted to theoretical studies of light pulse propagation through different linear and nonlinear media. One dimensional holographic photonic crystals and one dimensional impurity band based photonic crystals are investigated as linear media. The effects of angular dependence of the band structures and pulse delay with respect to the light polarization are analyzed. A strict theory of nonlinear propagation of a few strong interacting light beams is presented and applied in the field of nonlinear optics. The key idea of this approach is a self-consistent solution of the nonlinear wave equation and the density matrix equations of the material beyond the so-called rotating wave approximation. The results of numerical studies led to a successful interpretation of recent experimental data [<i>Nature</i>, 415:767, 2002]. A theoretical study of the NO molecule by means of two-color infrared -- X-ray pump probe spectroscopy is presented. It was found that the phase of the infrared field strongly influences the trajectory of the nuclear wave packet, and hence, the X-ray spectrum. The dependence of the X-ray spectra on the delay time, the duration and the shape of the pulses are studied.</p>
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Datorstött lärande på gymnasieskolan inom naturvetenskapliga ämnen : med speciell betoning på kemididaktiken.Bjarnason, Bjarni January 2006 (has links)
<p>Elever upplever allt som oftast svårigheter med den naturvetenskapliga undervisningen som ofta upplevs som abstrakt och overklig. De förklaringsmodeller som har beskrivits kring detta är att eleverna har svårigheter med att växla mellan makro (det man ser med ögat) och mikro (molekylär värld). I flera publikationer har man kunnat visa att för att nå en bred publik bör man aktivera så många sinnen som möjligt vilket är det som jag tar fasta på i detta arbete. Datormedierad multimedia framställning i undervisningen har, i publikationer, visat sig kunna kan skapa en bättre förståelse hos elever i kemi. Framförallt är det datorgenererad media framställning som simultant kan presenterar kemiska förlopp med olika representationer som har visat sig ge bra resultat. I denna studie har man kunnat visa att elever är mycket positiva till denna typ av framställning där man kan utföra experiment och se animeringar. De menar också själva att detta underlättar förståelsen av den molekylära världen. Genom att studera fall och kontroll kunde man även i denna studie visa på vissa skillnader i elevers kunskaper. De elever som fick möjlighet att studera animeringar och göra virtuella laborationer hade något bättre resultat än de som inte fick denna möjlighet.</p>
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Design and Synthesis of Hepatitis C Virus NS3 Protease InhibitorsJohansson, Anja January 2003 (has links)
Hepatitis C Virus (HCV) is the leading cause of chronic liver disease worldwide as well as the primary indication for liver transplantation. More than 3% of the world’s population is chronically infected with HCV and there is an urgent need for effective therapy. NS3 protease, a viral enzyme required for propagation of HCV in humans, is a promising target for drug development in this area. This thesis addresses the design, synthesis and biochemical evaluation of new HCV NS3 protease inhibitors. The main objective of the thesis was the synthesis of peptide-based protease inhibitors of the bifunctional full-length NS3 enzyme (protease-helicase/NTPase). Three types of inhibitors were synthesized: i) classical serine protease inhibitors with electrophilic C-terminals, ii) product-based inhibitors with a C-terminal carboxylate group, and iii) product-based inhibitors with C-terminal carboxylic acid bioisosteres. The developmental work included the establishment of an improved procedure for solid-phase peptide synthesis (SPPS) in the N-to-C direction, in contrast to the C-to-N direction of classical SPPS methods. This inverse method facilitated synthesis of the peptides modified at the C-terminal. The potency of more than seventy newly synthesized inhibitors was assessed in an in vitro assay using the native form of the protease, i.e. the full-length NS3. The structure-activity relationship (SAR) data achieved was different from SAR data obtained from the more widely used truncated NS3 (protease domain) assay, indicating that the helicase domain of NS3 participates in the binding of the inhibitors. The most potent inhibitors identified in this study contained a C-terminal phenyl acyl sulfonamide moiety, i.e. a carboxylic acid bioisostere. It is concluded that the acyl sulfonamide moiety is a promising P1-P1´ spanning entity, which may have potential for use in the development of more drug-like HCV protease inhibitors.
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