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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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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.