This present work investigates the NMR relaxation properties of a wide range of both healthy and leukaemic tissues to determine which tissues show the largest changes with disease development and to assess the timescale of these changes (white blood cell count was used to stage disease progression). The study makes use of a T-cell leukaemia animal model noted for its similarities to human lymphoblastic leukaemia animal studies of selected tissues assessed how well NMR changes related to pathological alterations in tissue structure and composition and identified possible causes for the observed NMR changes. Biochemical investigations were also performed to obtain a broader picture of the disease process. The sensitivity of another NMR technique known as Magnetization Transfer (MT) in the detection of leukaemic tissue changes was investigated. Various aspects of the instrumentation were developed, appropriate pulse sequences were written and suitable MT parameter settings for tissue experiments determined. Quantitative analysis of MT data was performed by fitting experimental results to a theoretical model for the MT process. Optimal MT parameter settings were established and the contribution of different processes to the MT effect were evaluated. Tissue postmortem NMR relaxation and MT properties were also investigated to determine the influence of postmortem measurement time in <I>in vitro</I> NMR results. Generally, it was found the NMR relaxation is more sensitive to disease development than MT. Liver showed the largest relaxation time changes although spleen showed the earliest significant changes. Therefore, tissues other than bone marrow show large NMR changes and would be worth investigating in a clinical environment. Also the different timescale of NMR changes between tissues may provide useful clinical information.

This research has investigated the validity of a recently proposed test for distinguishing erythro and threo diastereomers of RCHDCHDX compounds on the basis of temperature dependent nmr spectra. INDO and UMINDO semiempirical molecular orbital calculations were used to calculate all nmr vicinal proton-proton coupling constants of a series of CH3CH2CH2X compounds (X = BH2, CH3, NH2, OH, F, PH2, SH, Cl). These data were used to predict the relative temperature dependence of the time-averaged vicinal proton-proton coupling constants of the corresponding CH3CHDCHDX` compounds.Standard bond lengths and angles were used for the input of trial geometries. Coupling constant data were obtained for molecules with no geometry optimization, optimization of the CH3CCX dihedral angle and total geometry optimization. All results suggest that the proposed test for distinguishing erythro and threo diastereomers of RCHDCHDX compounds is valid.

This dissertation reports a study of three kinds of liquid crystals using modern solid state NMR techniques: chiral rod-like liquid crystals, bent-core mesogens and disc-like liquid crystals. The properties and structures of liquid crystals are first introduced in Chapter 1. To understand the principles of different NMR phenomena, quantum mechanical theory is adopted to study different nuclear spin interactions and NMR techniques in Chapter 2. In the next part of this dissertation (Chapter 3-6), deuterium NMR methods are used to investigate the dynamics and structures of some liquid crystal phases. This is first done using the spin relaxation study. The parameters obtained from the model simulation can describe the molecular motion and internal dynamics in the fast motion region. Secondly, we investigate the dynamic process of discotic mesophases and unwound smectic C* phase using the line shape simulation study. 2D deuterium NMR exchange experiments are then performed to study the jump process in TGBA* phase and SmC* phase. The above investigation has demonstrated some powerful NMR methods for the dynamic study of liquid crystals. The third part of the dissertation (Chapter 7-9) is concerned with C-13 NMR techniques. After we introduce the quantum theory of different pulse sequences, theoretical models are presented to fit observations such as chemical shifts and dipolar splittings. Moreover high resolution liquid C-13 NMR experiments are introduced to study some bent-core molecules. They are useful to assist the carbon peak assignments of these molecules. The structure and ordering information of liquid crystals can be determined in their mesophases. Finally, a brief summary of the dissertation is given in the last chapter.

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No description available.

Current theories of the effects of static and resonant high frequency magnetic fields on radical pair reaction are presented with a view to establishing how they can form the basis of the high time resolution liquid phase magnetic resonance techniques of MARY and RYDMR. Approximate calculations are performed to reveal RYDMR spectral details for the case of an initial triplet radical pair. The design of unique apparatus to explore the capabilities of the techniques, and routinely collect quantitative data to test theoretical predictions, is described. This includes the development of an ultra-fast waveform scan-digitizing facility which can attain effective sampling rates of up to 20 GHz. The apparatus is employed to provide the first demonstration of recombination exciplex fluorescence from pyrene - dicyanobenzene radical-ion pairs. It is also applied in the dimensional characterization of micellar and microemulsion media prior to their use in enhancing MARY and RYDMR signal intensities from solubilized radical pairs. By means of a laser induced radical fluorescence technique and compartmentalized reaction media, first observations are reported of optically detected RYDMR spectra from neutral radical pairs, the existence of very low field MARY spectral structure and the kinetic effect of a resonant microwave field. The MARY structure is attributed to Heisenberg exchange interaction and shown to be sensitive to microreactor volume.

No description available.

Here, we investigated the effects of modulation of the GABAergic system using a targeted neuropharmacological, 1H/13C NMR spectroscopy and metabolomic approach in Guinea pig cortical brain slices. The effects of exogenous GABA, agonists, antagonists and allosteric modulators at GABAA receptors were described and classified on the basis of metabolic activity; this corresponded to receptor location rather than pharmacology. The effects of agonists and antagonists at the GABAB receptor were described and classified into inhibitory and excitatory components, consistent with context dependent outcomes of receptor activity. Metabolic evidence for GABAC mediated activity in the cerebral cortex was identified for the first time indicating a strong role for this receptor in the control of neuronal activity. Inhibition of GABA uptake was examined using inhibitors of these transporters. The major effect of individual transporter subtype blockade was increased synaptic inhibition. The paradoxical activity of the GABA-transaminase inhibitor vigabatrin was resolved, with a direct demonstration of a single inhibitory mechanism mediated via this drug, via a mechanism also induced by antagonists at the GABAC receptor. These data were then integrated using multivariate statistics to identify 5 subclasses of activity which corresponded to receptor location (e.g. synaptic or extrasynaptic) rather than receptor pharmacology. This represents a novel and powerful new approach to the study of brain metabolism and the GABAergic system.

Here, we investigated the effects of modulation of the GABAergic system using a targeted neuropharmacological, 1H/13C NMR spectroscopy and metabolomic approach in Guinea pig cortical brain slices. The effects of exogenous GABA, agonists, antagonists and allosteric modulators at GABAA receptors were described and classified on the basis of metabolic activity; this corresponded to receptor location rather than pharmacology. The effects of agonists and antagonists at the GABAB receptor were described and classified into inhibitory and excitatory components, consistent with context dependent outcomes of receptor activity. Metabolic evidence for GABAC mediated activity in the cerebral cortex was identified for the first time indicating a strong role for this receptor in the control of neuronal activity. Inhibition of GABA uptake was examined using inhibitors of these transporters. The major effect of individual transporter subtype blockade was increased synaptic inhibition. The paradoxical activity of the GABA-transaminase inhibitor vigabatrin was resolved, with a direct demonstration of a single inhibitory mechanism mediated via this drug, via a mechanism also induced by antagonists at the GABAC receptor. These data were then integrated using multivariate statistics to identify 5 subclasses of activity which corresponded to receptor location (e.g. synaptic or extrasynaptic) rather than receptor pharmacology. This represents a novel and powerful new approach to the study of brain metabolism and the GABAergic system.

Proefschr. Rijksuniversiteit Groningen. / Met lit. opg.-Met samenvatting in het Nederlands.