Nuclear magnetic resonance (NMR) spectroscopy is one of the most important analytical tools for organic and biological chemistry. It provides not only detailed information on the structure of small molecules and macromolecules, but also on molecular interactions. Because of the inherent low sensitivity of NMR, a long signal averaging time or a high spin concentration is often required. A variety of methods have been explored to improve the sensitivity of NMR. Especially, large signal gains can be obtained by hyperpolarization of the nuclear spins. NMR signals of hyperpolarized samples are enhanced by several orders of magnitude. Dissolution Dynamic Nuclear Polarization (D-DNP) is a versatile technique capable of polarizing many different nuclei in the solid state, and subsequently providing a hyperpolarized liquid sample following a dissolution step. The resulting signal enhancement has made it possible to obtain detailed information in research fields as varied as metabolic imaging or enzyme catalysis. This dissertation aims to extend the applicability of D-DNP into new areas of chemistry, which involve the characterization of interactions and reactions involving large molecules. In a first project, fluorine hyperpolarization is exploited to investigate protein-ligand interactions. The enhancement of 19F signal allows for the detection of submicromolar concentrations of fluorinated ligands in the strong-, intermediate-, and weak-binding regimes. Several NMR parameters are utilized to observe ligand binding to the macromolecule, and to determine dissociation constants. In a second project, competitive binding of ligands to the same binding pocket on a protein is investigated. Here, polarization flows from a first ligand hyperpolarized on protons to the protein, and then to the second ligand. The buildup in function of time of the signals due to this relayed nuclear Overhauser effect contains structural information on the binding epitope. In a third project, the aim is to directly detect a larger molecule, a polymer, which has been synthesized starting from hyperpolarized monomers. Using DNP, single scan observation of 13C, a common nucleus with large chemical shift dispersion, is possible. Time resolved 13C NMR spectroscopy in combination with kinetic models permits the description of polymerization reaction of the living anionic polymerization of styrene. In summary, several approaches have been investigated for utilizing a large hyperpolarization initially produced on small molecules, for the benefit of characterizing properties of macromolecules. These developments extend the capabilities of D-DNP and demonstrate the potential for leading to new applications in fields as diverse as drug discovery and polymer science.

Würzburg, Univ., Diss., 2002.

Dortmund, Univ., Diss., 2002. / Computerdatei im Fernzugriff.

Dortmund, Univ., Diss., 2002. / Computerdatei im Fernzugriff.

München, Techn. Universiẗat, Diss., 2003.

Tübingen, Universiẗat, Diss., 2001.

Universiẗat, Diss., 2002--Würzburg. / Enth. 5 Sonderabdr. aus verschiedenen Zeitschr. und Publ. Erscheinungsjahr an der Haupttitelstelle: 2002.

Although charge order was discovered in \lndsco over two decades ago, this elusive state has not been as easily observable in \lsco. \cu NMR experiments demonstrated that \lsco did indeed transition into a charge ordering state, but the lack of evidence in other experiments made many physicists doubtful of its presence. With recent advancements in technology, x-ray scattering experiments have finally been able to measure charge order Bragg peaks in \lsco, proving that charge order anomalies seen by \cu NMR was legitimate. More recent \cu NMR showed that a broad wing-like signal emerges when charge order sets in in \lscoeleven with a much faster relaxation rate than the normal signal. In this thesis, we attempt to revisit the charge ordered state of \lsco by measuring \la NMR on single crystals of x~=~0.13, 0.115 and 0.10. By splitting the relaxation rate into two components, we were able to determine the temperature at which a fast component emerges, corresponding to the same temperature recorded by \cu NMR and x-ray scattering for the same \lscoeleven crystal. Using this method, we measured \la NMR lineshapes and spin-lattice relaxation rates and mapped out the charge order dome of the phase diagram of \lsco. / Thesis / Master of Science (MSc)

Many thousands of pounds are spent every year by pharmaceutical companies on understanding the mechanisms and kinetics of chemical reactions involved in drug discovery and production. NMR spectroscopy is often at the core of these studies as it is a powerful, non-destructive method for structure elucidation. As such investigations can be time-consuming and cost-inefficient, AstraZeneca, the project sponsor, is interested in more efficient methods for studying the kinetics of pharmaceutical reactions. In this work a number of different techniques have been devised, studied, and implemented to study the kinetics of chemical reactions by time-resolved NMR spectroscopy, in which every species in a reaction can be monitored simultaneously. These novel techniques allow the study of reactions which are difficult or impossible to study by conventional NMR methods (such as heterogeneous reactions), or which are complicated by having overlapping signals. It is possible to monitor the kinetics of a reaction very simply by acquiring a series of 1H spectra, and obtaining the integrals of the signals by least squares fitting. This technique has been used for kinetic studies of static and on-flow reactions. In the static systems the reaction mixture was placed in the normal NMR tube in the magnet, while in the flow system the reaction mixture was placed outside of the magnet, and the solution flowed through an NMR tube placed in the magnet. The novel flow system designed, constructed and tested here has been used for kinetic studies of illustrative homogeneous and heterogeneous reactions, and is suitable for use in a wide range of NMR instrumentation. Kinetic studies have also been carried out by acquiring a series of DOSY datasets, analysing the results using the multi-way method PARAFAC (PARAllel FACtor analysis). A series of DOSY datasets contains multivariate information on spectrum, time evolution and diffusion. Without providing any predetermined model, the data can be decomposed by PARAFAC to yield the spectrum, kinetics, and diffusion profiles for each of the components. It has also been shown that PARAFAC is remarkably robust to low signal-to-noise ratio data, significantly below the level at which conventional methods would fail.

Este trabalho consistiu na automação do espectrômetro de Ressonância Magnética Nuclear Pulsada existente no laboratório dos professores José Pedro Donoso e Claudio José Magon. Foram efetuados circuitos adicionais e melhorias no equipamento que eles possuíam, à nível de hardware e software. Foram construídas e programadas interfaces paralelas que ligam o microcomputador a um gerador de pulsos, fabricado pela Tecmag Inc., e a um digitalizador rápido (10 ns) Nicolet 430. O programador de pulsos pode acionar independentemente 75 linhas durante o intervalo de tempo subdividido em 2048 eventos, também independente. O software desenvolvido permite a programação de todas as linhas e eventos de forma eficiente e prática. Foi todo escrito em linguagem C, é modular, portátil, e permite a geração de seqüências de pulsos sofisticadas e também o controle da aquisição e transferência de dados / This work describes the Project developped to automatize the pulsed nuclear magnetic resonance spectrometer housed in the laboratory of the professors José Pedro Donoso e Cláudio José Magon. To satisfy our needs we have improved their old equipment, at the level of hardware and software. Were built and programmed the parallel interface between the microcomputer and a pulse programmer made by Tecmag Inc. and with a fast digitizer (10 ns) Nicolet 430. The pulse programmer can control 75 independent output channels during 2048 time intervals. The software we developped allow us to control the whole pulse sequence on a very efficient and practical way. It was written in C-language, and provides the timing signals necessary to generate sofisticated pulse seqüencies, the data acquisition and data transfer to the host computer