The use of driven equilibrium conditions in the measurement of NMR relaxation times

The further development of the use of NMR relaxation times in chemical, biological and medical research has perhaps been curtailed by the length of time these measurements often take. The DESPOT (Driven Equilibrium Single Pulse Observation of T1) method has been developed, which reduces the time required to make a T1 measurement by a factor of up to 100. The technique has been studied extensively herein and the thesis contains recommendations for its successful experimental application. Modified DESPOT type equations for use when T2 relaxation is incomplete or where off-resonance effects are thought to be significant are also presented. A recently reported application of the DESPOT technique to MR imaging gave good initial results but suffered from the fact that the images were derived from spin systems that were not driven to equilibrium. An approach which allows equilibrium to be obtained with only one non-acquisition sequence is presented herein and should prove invaluable in variable contrast imaging. A DESPOT type approach has also been successfully applied to the measurement of T1. T_1's can be measured, using this approach significantly faster than by the use of the classical method. The new method also provides a value for T1 simultaneously and therefore the technique should prove valuable in intermediate energy barrier chemical exchange studies. The method also gives rise to the possibility of obtaining simultaneous T1 and T1 MR images. The DESPOT technique depends on rapid multipulsing at nutation angles, normally less than 90^o. Work in this area has highlighted the possible time saving for spectral acquisition over the classical technique (90^o-5T_1)_n. A new method based on these principles has been developed which permits the rapid multipulsing of samples to give T_1 and M_0 ratio information. The time needed, however, is only slightly longer than would be required to determine the M_0 ratio alone using the classical technique. In ^1H decoupled ^13C spectroscopy the method also gives nOe ratio information for the individual absorptions in the spectrum.

Development of novel NMR pulse sequences

To elucidate the structures of orgamc molecules in solution using pulse FT NMR, heteronuclear pulse sequence experiments to probe carbon-13 (13C) and proton (1H) spin systems are invaluable. The one-dimensional insensitive nucleus detected PENDANT experiment finds popular use for structure determination via one-bond 13C-1H scalar couplings. PENDANT facilitates the desired increase in 13C signal-to-noise ratio, and unlike many other pulse sequence experiments (e.g., refocused INEPT and DEPT), allows the simultaneous detection of 13C quaternary nuclei. The tlrst chapter herein details the characterisation of PENDANT and the successful rectification of spectral anomalies that occur when it is used without proton broadband decoupling. Multiple-bond (long-range) l3C-1H scalar coupling correlations can yield important bonding information. When the molecule under scrutiny is devoid of proton spectral crowding, and more sensitive 'inverse' pulse sequence experiments are not available, one may use insensitive nucleus detected long-range selective one-dimensional correlation methods, rather than more time consuming and insensitive multidimensional analogues. To this end a novel long-range selective one-dimensional correlation pulse sequence experiment has been invented. Based on PENDANT, the new experiment is shown to rival the popular selective INEPT technique because it can determine the same correlations while simultaneously detecting isolated 13C quaternary nuclei. INEPT cannot facilitate this, potentially leaving other important quaternary nuclei undetected. The novel sequence has been modified further to yield a second novel experiment that simultaneously yields selective 13C transient nOe data. Consequently, the need to perform the two experiments back-to-back is conveniently removed, and the experimental time reduced. Finally, the SNARE pulse sequence was further developed. SNARE facilitates the reduction of experimental time by accelerating the relaxation of protons upon which pulse sequences, to which SNARE is appended, relies. It is shown, contrary to the original publication, that reiaxation time savings can be derived from negative nOes.

NMR spectroscopy in the presence of ultrasound and other perturbations

The work described in this thesis has been concerned with exploring the potential uses of ultrasound in Nuclear Magnetic Resonance (NMR) spectroscopy, The NMR spectra of liquids provide detailed structural information that may be deduced from the chemical shifts and spin-spin coupling, that are evident in the narrow resonances, arising from some of the nuclear broadening interactions being reduced to zero. In the solid state, all of the nuclear broadening interactions are present and broad lines in the NMR spectrum are observed. Current techniques employed to reduce the line widths in solids are based on coherent averaging techniques such as MAS NMR1,2 which can remove first order interactions. Recently DOR3 and DAS4 have become available to remove higher order interactions. SINNMR (Sonically Induced Narrowing of the NMR spectra of solids) has been reported by Homer et al5 and developed by Homer and Howard6 to reduce the line widths of solids. The basis of their work is the proposal that a colloidal suspension of solid particles can be made to move like large molecules by using ultrasonic agitation. The advantage of the technique is that the particles move incoherently removing all of the nuclear interactions responsible for broad lines. This thesis describes work on the extension of SINNMR by showing that the line width of 27AI and 11B for the glass Na20/B203/AI203 can be reduced by placing solid particles in a colloidal suspension. Further line width reduction is possible by applying ultrasound, at 2 MHz, of sufficient intensity. It is proposed that a cavitation field is responsible for imparting sufficient rotational motion to the solid particles to partially average the nuclear interactions responsible for broad lines. Rapid stirring of the colloidal suspension generates turbulent flow, however, the motion is insufficient to narrow the line widths for 27AI in the glass. Investigations of sonochemical reactions for in situ rate measurements by NMR have been made. 8y using the Weissler reaction7, it has been shown that ultrasonic cavitation is possible up to 10MHz. Preliminary studies have been carried out into the rate of ultrasonic polymerisation of methylmethacrylate by NMR. Long range order in liquid crystals can imposed when they are aligned in the presence a magnetic field. The degree of alignment can be monitored by NMR using, for example a deuterated solute added to the liquid crystal8. Ultrasonic streaming can then be employed to deflect the directors of the liquid crystal from their equilibrium position, resulting in a change In the NMR spectrum. The angle of deflection has been found for the thermotropic liquid crystal (I35) to be ca, 35° and for the lyotropic (ZLI-1167) to be ca, 20°, Mechanical stirring can used to re- orientate the liquid crystal but was found to give a smaller deflection, In a separate study, that did not use ultrasound, it has been found that the signal to noise ratio of 13C NMR signals can be enhanced by rapidly stirring a Iiquid. Accelerating the diffusion of nuclei out of the coil region enables M0 to be re-established more rapidly than the normal relaxation process. This allows the pulse repetition rate to be reduced without saturating the spin system. The influence of varying the relaxation delay, acquisition time and inter-pulse delay have been studied and parameters optimised. By studying cholesterol the technique was found to be most effective for nuclei with long relaxation times, such as quaternary carbon sites. Key Worde: NMR, Ulf.rasciund, 1,.lqi.fi!:l cryllltalt!h SCll1C1otlemlstryl I!r1hano~d algnflllf