Towards analytical applications using SABRE-hyperpolarised benchtop NMR

Benchtop NMR spectrometers offer an accessible analytical platform due to their low acquisition
and operation costs, as well as their portability. However, their lower magnetic
field strength (1 - 3 T) results in reduced sensitivity and chemical shift dispersion compared
to high-field systems (≥ 7 T), limiting their widespread use in routine analysis. This
thesis explores the potential of benchtop NMR in combination with the hyperpolarisation
technique signal amplification by reversible exchange (SABRE), as an accessible and sensitive
analytical technique. A special focus is placed on 19F NMR measurements to mitigate
spectral congestion.
Integrating SABRE with the multiplet-refocusing pulse sequence SHARPER led to
significant signal-to-noise ratio (SNR) enhancements, as demonstrated in 19F NMR measurements
on a set of fluoropyridines exhibiting diverse scalar coupling patterns. By the
combined effects of SABRE and SHARPER, SNR enhancements of up to 5700-fold were
achieved. A novel variation of the selective SHARPER pulse sequence enabled simultaneous
signal isolation and enhancement for each component of a binary mixture, minimising
signal loss compared to previous versions. The boost in signal enhancement afforded by
SABRE-SHARPER was harnessed to decrease detection limits for this technique, aided by
the use of co-substrates to form a stable polarisation transfer catalyst, resulting in a submicromolar
limit of detection for a model fluoropyridine target. The use of co-substrates
also facilitated the micromolar quantification of this target with an excellent degree of
accuracy and precision.
The scope for this technique was further explored by probing a fluoroamine target, which
contains exchangeable protons and is susceptible to polarisation deviation via SABRE Relay.
Although this unwanted process leads to a sensitivity penalty, which can be minimised
by deuteration of the exchangeable protons, low micromolar limits of detection and
accurate quantification is shown for this analyte. In contrast, fluorocarboxylic acids posed
greater challenges. SABRE enhancements were observed exclusively for their carboxylate
forms and remained modest, with operational detection limits in the low millimolar range.