Recently, there is a growing interest in applying electronic circuit design for biomedical applications, especially in the area of nuclear magnetic resonance (NMR). NMR has been used for many years as a spectroscopy technique for analytical chem- istry. Previous studies have demonstrated the design and fabrication of planar spiral inductors (microcoils) that serve as detectors for nuclear magnetic resonance mi- crospectroscopy. The goal of this research was to analyze, design, and test a prototype integrated sensor, which consisted of a similar microcoil detector with analog components to form a multiple-channel front-end for a magnetic resonance imaging (MRI) system to perform microspectroscopy. The research has succeeded in producing good function- ality for a multiple-channel sensor. The sensor met expectations compared to similar one-channel systems through experiments in channel separation and good signal-to- noise ratios.

The study of the mechanism of action of an antitumor active drug is essential for improving the efficacy and reducing the side effects of the drug as well as for developing better alternatives. In this vein, reactions of dirhodium compounds with DNA oligonucleotides were investigated by the techniques of mass spectrometry, HPLC, and NMR spectroscopic analytical methods. The relative reactivities of three dirhodium compounds, namely Rh2(O2CCH3)4, Rh2(O2CCF3)4, and [Rh2(O2CCH3)2(CH3CN)6](BF4)2, with DNA oligonucleotides were studied and compared to the clinically used anticancer drugs cisplatin and carboplatin using both MALDI and ESI mass spectrometric methods. The compound Rh2(O2CCF3)4 exhibits the highest reactivity among the dirhodium compounds, which is comparable to cisplatin, followed by [Rh2(O2CCH3)2(CH3CN)6](BF4)2, and finally Rh2(O2CCH3)4 which is the least reactive. Various dirhodium-oligonucleotide adducts were detected with both MALDI and ESI methods, which involve substitution of different numbers of the original ligands of the given dirhodium compound. ESI MS was found to be a sufficiently soft ionization method for detecting intact metal adducts, and CID MS-MS was useful for detecting weakly bound species such as axial adducts [M+Rh2(O2CCH3)4] and for comparing the relative bond strength between ligands in the metal adduct. A combination of anion exchange HPLC purification and enzymatic digestion studies of the adducts of Rh2(O2CCH3)4 with the 5'-CCTTCAACTCTC oligonucleotide revealed that Rh2(O2CCH3)4 binds to the center or to the ends of the oligonucleotide sequence by displacement of one or two acetate groups. Kinetic products of the type [M+Rh2(O2CCH3)3] obtained from the reaction of Rh2(O2CCH3)4 with 5'-CTCTCAACTTCC were separated by employing both reverse phase and anion exchange HPLC methods. The adduct that involves binding of the dirhodium unit to the exocyclic N4 atom of C5 and the N7 of A6 was found to be most stable whereas other adducts involving binding of C3 or C12 residues are clearly less stable. Reaction of cis-[Rh2(DAP)(O2CCH3)3(CH3OH)](O2CCH3) (DAP = 1,12- diazaperylene) with 5'-CTCTCAACTTCC produced a major adduct in which DAP group intercalates between 6A and 7A in the double stranded adduct with the rhodium atom that is not coordinated to the DAP group forming a covalent bond to the N7 atom of 6A which lends stability to the adduct.

In den vergangenen Jahren wurden anorganische Salzhydratschmelzen und Ionic Liquids als neuartige Reaktions- und Lösemedien für Cellulose etabliert. Ausgangspunkt für die vorliegende Arbeit zum Lösungszustand von Cellulose in Salzschmelzen war, ein Verständnis für die strukturelle Veränderung beim Auflösen von Cellulose in diesen Solventien zu entwickeln, sowie einen Zusammenhang zwischen der Cellulosestruktur in Lösung und der im Regenerat herzustellen. Auf der Grundlage NMR-spektroskopischer Untersuchungen wurde eine direkte Wechselwirkung zwischen bevorzugten Hydroxylgruppen der Cellulose und den Lithiumkationen der Salzhydratschmelze LiCl∙5D2O nachgewiesen und eine konkrete Lösungsstruktur vorgeschlagen. Unter Verwendung von schwingungsspektroskopischen Methoden und der 13C-CP/MAS-NMR wird die Struktur der Cellulose im festen Salzhydrat als amorph charakterisiert. NMR-Untersuchungen an unkonventionell synthetisierten Cellulosederivaten liefern neue Erkenntnisse zu deren Ordnungsgrad und Substitutionsmuster.

Zugl.: Halle (Saale), Univ., Diss., 2005 / Hergestellt on demand

Würzburg, Universität, Thesis (doctoral), 2001.

Bremen, Universität, Thesis (doctoral), 2000.

En metod som kan användas för att extrahera opolära narkotika- och läkemedelssubstanser ur matriser med ett högt fettinnehåll har tagits fram. Metoden är baserad på ett extraktionsprotokoll från Livsmedelsverket (SLV K1-f4-m018.3) som används för analys av bekämpningsmedel i animaliska livsmedel. Metoden har sedan optimerats för forensiska applikationer genom att ändra olika variabler. Två av variablerna som testades var olika typer av extraktionsmedel och mängden tillsatt C18 (oktadekylsilyl)-sorbent. Experimenten visade att acetonitril som extraktionsmedel och en ökad tillsats av C18 eliminerade den största andelen av fettmolekylerna i matrisen utan att kompromissa med utbytet av den undersökta analyten. Analyterna som undersöktes var 5F-AKB48, tetrahydrocannabinol (THC) och alprazolam och den fettinnehållande matrisen utgjordes av smör. Metoden lyckades minska fetthalten i smörproverna från ca 80- till 3-5 % fett samtidigt som ett utbyte av analyterna erhölls på 70-90 %. Analyten med högst utbyte efter extraktionen var 5F- AKB48 med ett utbyte på cirka 90 %. Utbytet för alprazolam och THC blev 72- respektive 75 %. Vid extraktion med etylacetat, som var det extraktionsmedel som användes i den ursprungliga metoden (SLV K1-f4-m018.3), erhölls inga minskningar av fetthalten överhuvudtaget utan hamnade runt 80 % i samtliga analyser. När metodens kapacitet testades med ökade fetthalter visade det sig att fetthalten efter extraktionen blev lägre i de prover som hade en högre fetthalt från början. Utbytet av analyten (5F-AKB48 i detta fall) påverkades däremot inte nämnvärt av de ökade fetthalterna utan höll sig stabilt runt 85 %.

Computational modelling of chemical systems is most easily carried out in the vacuum for single molecules. Accounting for environmental effects accurately in quantum chemical calculations, however, is often necessary for computational predictions of chemical systems to have any relevance to experiment. This PhD thesis focuses on accounting for environmental effects in quantum chemical calculations by quantum mechanics/ molecular mechanics (QM/MM) approaches, taking on diverse examples from the solid state, the liquid phase and the protein environment. The methods are applied to compute a variety of properties from transition metal NMR properties of molecular crystals and enzymes, via conformational properties of zwitterions in aqueous solution, to an intramolecular amidation reaction in peptides. Chapter 3 concerns QM/MM calculations of molecular properties in the solid state, both molecular crystals and metalloenzymes, with a focus on transition metal chemical shift and EFG properties. We demonstrate that solid-state effects on such properties in molecular crystals can be accounted for by a simple general black-box QM/MM approach. We also describe preliminary QM/MM calculations of 51V anisotropic NMR properties for a vanadium-dependent enzyme. In Chapter 4 the focus is on solvent effects on the conformational preference of a small zwitterionic molecule, 3F-γ-aminobutyric acid (3F-GABA), calculated using QM/MM molecular dynamics simulations. NMR spin-spin coupling constants in solution are also calculated. Our simulations highlight the difficulty of accounting for solvation effects well enough to achieve agreement with experimental observations. Chapter 5 concerns the reaction mechanism of an intramolecular amidation reaction in a bacterial peptide, predicted by QM/MM calculations. We predict a reaction mechanism that accounts well for the experimental observations both for the wild-type and mutants. We demonstrate that environmental effects can often be satisfactorily accounted for by QM/MM approaches, thus helping to bridge the gap between theory and experiment.

This thesis describes the development of hyperpolarized silicon particles as a new type of magnetic resonance imaging (MRI) agent. Silicon particles are inexpensive, non-toxic, biodegradable, targetable, and have unique physical properties that lead to extremely long nuclear polarization times. The \(^{29}Si\) nuclei are hyperpolarized by low temperature dynamic nuclear polarization using naturally occurring defects at the particle surface and directly imaged using \(^{29}Si\) MRI. The imaging window achievable is several orders of magnitude longer than other hyperpolarized imaging agents. The technique requires no additional imaging agent to be incorporated into the silicon, and so toxicity complications are reduced. The construction of a system for low temperature dynamic nuclear polarization and a NMR spectrometer for studying the nuclear polarization dynamics in silicon particles is described. Room temperature nuclear spin relaxation \((T_1)\) times are investigated for a variety of silicon particles spanning five orders of magnitude in mean diameter, from 10nm nanoparticles to mm-scale granules. The nuclear \(T_1\) times of all Si particles are found to be long, ranging from many minutes to several hours at room temperature. \(T_1\) is found to be a function of particle size, dopant concentration, synthesis method and crystallinity. A core-shell model to describe the electron and nuclear spin dynamics in the particles is developed. The decay in nuclear hyperpolarization is studied as a function of ambient magnetic field and temperature, demonstrating that the long spin relaxation times persist despite changing environmental conditions. A new technique is reported for enhancing the dynamic nuclear polarization in silicon particles using modulated microwave irradiation. A theoretical model for understanding this enhanced polarization process is developed. As well as providing an efficient mechanism for polarizing the \(^{29}Si\) nuclei within the particle, the surface defects are also found to be efficient at polarizing \(^1H\) nuclei in frozen solutions surrounding the particles. Several in-vivo applications of hyperpolarized \(^{29}Si\) MRI are demonstrated, including gastrointestinal imaging, intravenous imaging and mapping blood flow in a tumor. The spin relaxation rates are found to be unaffected by surface functionalization, the particles tumbling in solution, or the in-vivo environment. / Engineering and Applied Sciences

In protein NMR spectroscopy, homonuclear mixing pulses are used to reveal correlations amongst chemically bonded nuclear spins. / Engineering and Applied Sciences