New NMR methods and their applications in mechanistic studies
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Date
20/02/2023Item status
Restricted AccessEmbargo end date
20/02/2024Author
Wei, Ran
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Abstract
Tracing the fate of fast irreversible chemical reactions remains a challenging and intriguing
task in chemistry. While slow reactions can be monitored by routine NMR techniques at ease,
real-time monitoring of fast reactions that are initiated by mixing, however, poses challenges
to traditional NMR experiments and therefore requires specialised techniques. A state-of-theart
stopped-flow piece of equipment was utilised in conjunction with a high-resolution NMR
spectrometer, to enable the data collection of rapid reactions including identification of
intermediates, side-products, and catalysts, and quantification of selectivity. This work consists
of three main aspects regarding the stopped-flow technique: i) evaluating the physical
parameters and functionalities of the stopped-flow instrument; ii) monitoring rapid irreversible
reactions with half-lives shorter than seconds; and iii) exploiting the non-pre-magnetised input
channel of the stopped-flow instrument for magnetisation transfer studies. Thus far, effective
kinetic data collection for irreversible chemical reactions of half-lives in the order of
milliseconds was achieved, with the aid of interleaved stopped-flow experiments. This was
demonstrated by the base-catalysed protodeboronation of pentafluorophenyl boronic acid, of
t1/2 = 45 milliseconds at 313 K. The functionality of the non-pre-magnetised stopped-flow input
channel was experimentally validated by the chemical exchange studies without the necessity
of isotopic labelling. In addition to the stopped-flow technique, a closely-related yet
independent work on the measurements of longitudinal relaxation time constant (T1) was
conducted. T1 is an important NMR parameter essential for quantitative NMR experiments and
molecular dynamic studies. Therefore, prior to kinetic analysis, it is necessary to measure the
T1 of spins in the system. Comparing to the most conventional approaches such as the
‘Inversion Recovery’ experiments, the methodologies developed in this work showed
significant improvements in time efficiency and achieved sufficiently accurate T1
measurements. Furthermore, it was proved that continuous heteronuclear decoupling could be
applied in T1 measurements, affording sensitivity enhancements from the removal of Jcouplings
and the Nuclear Overhauser Effects. This application is particularly beneficial for
insensitive nuclei, which intrinsically require longer experimental time. Throughout the
developments of T1 methods with heteronuclear decoupling, a range of decoupling schemes
were evaluated to highlight the appropriate choice for different spin systems.