AbstractAdvanced Methods for Formulation Analysis is authored by Iain Swan and submitted for the degree of Doctor of Philosophy in the Faculty of Engineering and Physical Sciences at the University of Manchester, on 21 September 2015.This thesis concentrates on diffusion-ordered spectroscopy (DOSY): a technique in liquid state nuclear magnetic resonance (NMR) spectroscopy that is able to distinguish different chemical species by their size in solution, and measure species' diffusion coefficients. DOSY is an invaluable tool to analyse and resolve the signals of mixtures of chemicals in solution. DOSY measures an ensemble of nuclei in a mixture, using pulsed field gradients (PFGs) to encode, and later decode, the positions of spins. This provides information on the root mean square distance that spins diffuse during a delay between a pair of PFGs, which allows the determination of diffusion coefficients. However, DOSY is susceptible to a number of complications.Where a sample convects, the distance molecules move during the delay is greater than for simple diffusion, and the estimate of the diffusion coefficient becomes greater than the true value. Rayleigh-Bénard convection has been known in NMR for a long time, and is known to result from heating the base of an NMR sample, giving rise to negative vertical temperature gradients. Here, cooling the base (and inadvertently the sides) of the sample is also shown to cause convection from transverse temperature gradients, known as Hadley convection and commonly observed in atmospheric circulation. The theory for convection from transverse temperature gradients is given and recommendations to reduce convection in NMR are made.DOSY analysis can also be challenging where signals from different species overlap. In such instances, it can help to reduce the overlap, which can be achieved by collapsing multiplets into singlet signals: pure shift NMR is a technique that uses band-selection in order to refocus scalar coupling during the free induction decay, leaving pure chemical shift information. However, PFGs can vary in strength across the sample, which can have an effect on band selective experiments, such as Zangger-Sterk pure shift experiments, in the measured peak amplitudes, and where DOSY is combined with the Zangger-Sterk pure shift sequence, the apparent diffusion coefficients are also altered, seemingly as a function of chemical shift. A correction for this is given, simply using a DOSY and a DOSY pure shift experiment, as an alternative to the current literature method (gradient mapping).An investigation into an emulsion, agrochemically important for the delivery of active ingredients (fertiliser,pesticides, etc.) to plants, was then undertaken, in the hopes of finding restricted diffusion, but instead discovering substantial chemical exchange on the diffusional timescale.Finally a program was written for the automated acquisition of DOSY data, without the need for a human controller to calibrate DOSY parameters for the optimum acquisition.
|Date of Award||31 Dec 2015|
|Supervisor||Mathias Nilsson (Supervisor) & Gareth Morris (Supervisor)|