High-resolution Nuclear Magnetic Resonance and Mass spectrometry methodology for the analysis of complex mixtures

Background behind the proposed research. Complex mixtures are all around us and have a great
impact on our daily lives. Natural organic matter of soils, rivers, oceans or aerosols, food and
beverages, bio-fluids or biologic medical products are all examples of very complex mixtures. The
status quo in compound identification is to expend lots of energy combating the second law of
thermodynamics to try to isolate individual compounds from a mixture. However, wouldn't it be
wonderful if we did not have to go through such an arduous process and were able to simply bypass
the customary purification step? This is particularly relevant, as the separation of individual
compounds from a mixture of thousands of molecules is beyond the capability of today's
chromatographic methods.2
The methodology I aim to develop will be relevant to environmental issues, food and medicine
production and regulation.
Methodology. NMR spectroscopy and mass spectrometry are the two state-of-the-art highresolution
techniques that have the potential to tackle the analysis of complex mixtures at a
molecular level.3,4 The hardware and software capabilities of NMR and MS spectrometers are
constantly improving, opening doors for the development of new methodology. The School of
Chemistry of the University of Edinburgh is one of only two UK universities that houses both cutting
edge NMR and MS spectrometers (800 MHz NMR cryoprobe instrument and 12 T FT-ICR mass
spectrometer). Researchers here also have access to the world-leading NMR and MS equipment of
the Pacific Northwest National Laboratory (PNNL), USA.
An overarching aim of my research thus is to advance NMR and MS methodology for the
analysis of complex mixtures by developing new methods for data acquisition, processing
and analysis.
My objectives. To apply the developed methodology to answer important questions concerning real
life complex mixtures:
(i) Disinfection by-products (DBPs) in drinking water
(ii) Scotch whisky
(iii) Biological medicines
Research questions and hypotheses. Each of the above objectives poses a unique research
question that is briefly elaborated on in the following paragraphs.
(i) Characterisation of DBPs generated during the production of potable water. Extensive physical
and chemical treatment is required to reduce the levels of dissolved organic matter (DOM) below 2
mg/l when microbial disinfectant can be applied. In Scotland, this involves chlorination/
chloramination. In addition to dealing with microbes, radical reactions involving DOM molecules
produce hundreds of chlorinated molecules that become part of potable water.5 At present only a
handful of these is regulated, as the structures of a vast majority of DBPs are unknown. Knowing
structures of DBPs is essential if we are to determine their potential effects on human health.
Hypothesis. A single fluorine atom used as a tag on DOM constituent molecules (representing
different classes of DOM molecules) will allow structure determination of DBPs through newly
developed NMR and MS methodology. This approach is necessary since Cl is not "a NMR friendly
nucleus", which is in complete contrast to 19F that has 100% natural abundance, high sensitivity,
large chemical shift range and far reaching couplings with 1H and 13C, facilitating structure
determination. Chlorine isotopes on the other hand a