Improving the resolution of quantitative NMR

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is often described as an intrinsically quantitative technique, as signal integrals are directly proportional to the number of nuclei that generate the signal. Whilst all NMR experiments are intrinsically quantitative, in the strictest interpretation, only the simple pulse-acquire experiment is ‘universally quantitative’, meaning that the relative integrals of different signals represent the relative numbers of spins which give rise to those signals. Proton (1H) pulse-acquire NMR spectra, however, frequently exhibit a high degree of signal overlap due to the narrow range of 1H chemical shifts and extensive signal multiplicity. The inability to clearly resolve signals complicates the extraction of accurate signal integrals with which to perform quantitation. To resolve this signal overlap, users may turn to high-resolution multiple-pulse NMR experiments, but these almost always introduce site-dependent signal loss and are therefore not universally quantitative. Various approaches have been developed to perform quantitation with multiple-pulse NMR experiments. The most commonly used is the calibration curve method, which establishes the relationship between absolute integral and the concentration of a particular analyte for a given experiment. Alternative strategies involve designing multiple-pulse NMR experiments in which either the specific attenuation factor of each signal can be measured (and thus corrected for), or in which these attenuation factors are engineered to be more uniform. The aim of this thesis is to describe novel developments that improve the quantitative performance of high-resolution NMR experiments. Presented in this thesis are methods which permit the acquisition of high-resolution quantitative NMR data, or represent progress towards this aim. Chapter 2 and 3 contain introductions to the relevant NMR theory and quantitative NMR principles and methods, which provide context for the research presented in this thesis. Chapter 4 is comprised of research that offers a practically useful description of spin relaxation during slice-selective refocusing pulses. Chapter 5 and 6 present methods to obtain universally quantitative high-resolution NMR data. Chapter 7 summarises the research presented in this thesis, and offers suggestions to improve or extend upon this research.

Date of Award	1 Aug 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Gareth Morris (Supervisor), Mathias Nilsson (Supervisor) & Ralph Adams (Supervisor)