Hydrogen bonding plays a key role in determining the molecular-level structure and dynamics of most organic systems. To fully understand this interaction and potentially exploit it for the design of new materials, the development and implementation of suitable analytical techniques is essential. The highly localised nature of solid-state NMR makes it a powerful probe of structure and dynamics. In particular, the IH chemical shift is a sensitive indicator of local environment, thereby providing a direct insight into hydrogen-bonding interactions. However, in comparison to other solid-state NMR techniques, IH solid-state NMR is very challenging due to the extensive spectral line broadening that results from strongly dipolar-coupled proton networks. Nevertheless, recent advances in solid-state NMR technology and methodology allow high-resolution IH NMR spectra to be obtained for these challenging systems. In this thesis, advanced solid-state NMR techniques and methodology are implemented in order to gain structural insight into a range of biologically and pharmaceutically relevant systems. A combined approach incorporating IH doublequantum (DQ) magic-angle spinning (MAS) NMR and single-crystal diffraction data is used to characterise supramolecular self-assembly in a group of novel nucleoside derivatives. High-resolution IH DQ combined rotation and multiple pulse spectroscopy (CRAMPS) NMR experiments are implemented to .provide a detailed insight into pseudo-polymorphic forms of an active pharmaceutical ingredient in a tablet formulation. This work constitutes a new tool for pseudo-polymorphic characterisation, with important implications for industry. The· concept of solid-state NMR crystallography is demonstrated for a challenging but biologically important disaccharide, for which a full IH resonance assignment is presented for the first time through a combined experimental and computational approach incorporating ab initio chemical shift calculations. This method is extended to the study ofthree polymorphs of paracetamol, where the hydrogen-bonding arrangement is characterised for a polymorph with an as-yet unsolved crystal structure. Additionally, experimental and numerically simulated results are presented for a low-load IH heteronuclear spin decoupling technique; this new approach shows good potential for use in MAS spin-echo experiments which can quantify hydrogen-bonding strength through the measurement of hydrogen-bond mediated J-couplings.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:491930 |
| Date | January 2007 |
| Creators | Griffin, John Matthew |
| Publisher | University of Warwick |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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