Resolving complex mixtures of molecules by pH gradient NMR spectroscopy (WALLACEM_U25SCI)

Primary Supervisor – Dr Matthew Wallace

The quest for new pharmaceuticals or the study of living systems usually involves horrendously complex mixtures of organic molecules; be they from cell lysates, microbial fermentations or organic reactions. Identification of the compounds present is necessary to determine activity, facilitate successful isolation and optimise chemical or biological syntheses. Nuclear magnetic resonance (NMR) spectroscopy has emerged as a powerful tool for complex mixture analysis as each molecule necessarily exhibits a unique NMR fingerprint in terms of chemical shifts, J-couplings and relaxation rates (1). However, the sheer number of molecules involved can render the interpretation of NMR spectra incredibly difficult due to the large number of overlapping resonances. 

In this project, you will introduce a completely new tool to the field of complex mixture analysis by combining controlled pH and calcium gradients with spatially resolved NMR. Pioneering research in our group has demonstrated how properties such as the acid dissociation constant (pKa) can be determined in a highly efficient manner using this approach, including in organic solvents and aqueous/organic mixtures (2). As pKa is a unique and diagnostic property of a molecule, applying our techniques to complex mixtures is likely to create a powerful method to identify unknown molecules. 

You will receive a sound training in advanced NMR spectroscopy, analytical chemistry (chromatography) and data processing. Working collaboratively with researchers at the University of East Anglia and the Quadram Institute, you will apply your methods to identify promising pharmaceutically active compounds in extracts of plants as well as key intermediates in the cycling of sulphur in the oceans and in the metabolism of microbes in the human gut (3).

Entry Requirements

The standard minimum entry requirement is 2:1 in Chemistry, Pharmacy, Pharmacology, Physics or a related discipline 

Mode of study

Full Time

Start date

1 October 2025