Dr Meghan Halse

01904 322853
Email: meghan.halse@york.ac.uk

Nuclear Magnetic Resonance (NMR) Spectroscopy

My research focuses on the development of new nuclear magnetic resonance (NMR) methods with a particular focus on the use of hyperpolarisation to open up new and exciting applications for this technique.

Magnetic resonance (MR) is an invaluable tool for applications ranging from chemical analysis to clinical diagnosis. The power of MR lies in the wealth of molecular-level information available and the selectivity and control provided by the use of radio-frequency irradiation and magnetic field gradients to tune the evolution of the MR signals.  In magnetic resonance, the signal arises from the difference in population between nuclear spin states in the presence of an external magnetic field. Even at the highest available magnetic field (currently 23.5 T), this population difference is so small that only 1 in every 12,000 nuclear spins contribute to the observed signal. Given this inherent low sensitivity, the success of nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) is quite remarkable.

Hyperpolarisation is a general term used to describe the generation of nuclear spin population differences that are orders of magnitude larger than the thermal distribution dictated by Boltzmann statistics. These methods require a source of spin order that can be transferred to the target nuclear spins. One method that has shown a lot of potential in recent years is parahydrogen induced polarisation (PHIP). Parahydrogen (p-H2) is the thermally preferred nuclear spin isomer of molecular hydrogen. It exists in a pure nuclear singlet state, which has no net magnetic moment and so is NMR silent. However, when the symmetry of the environments of the two 1H nuclei in p-H2 is broken, through oxidative addition at a metal centre or hydrogenation of an unsaturated substrate for example, this pure singlet state evolves into observable magnetisation. Due to the purity of the initial state, the resultant NMR signals are orders of magnitude larger than the corresponding thermal signals.

Researchers at York, led by Professor Simon Duckett, have recently developed a new approach to parahydrogen hyperpolarisation called signal amplification by reversible exchange (SABRE). In SABRE the spin order from p-H2 is transferred to a substrate catalytically, without the need to chemically change the substrate. The transfer of polarisation is mediated by a transition metal catalyst that reversibly binds p-H2 and one or more molecules of the substrate, establishing a coupling network that promotes the transfer of spin order from the former-p-H2 nuclei to the substrate. Subsequent exchange of the hyperpolarised bound substrate gives rise to a reservoir of hyperpolarised free substrate in solution.

SABRE: The interaction of parahydrogen and a substrate while weakly bound to a transition metal leads to strong hyperpolarisation of the substrate.

SABRE: The interaction of parahydrogen and a substrate while weakly bound to a transition metal leads to strong hyperpolarisation of the substrate.

In collaboration with Professor Duckett and the Centre for Hyperpolarisation in Magnetic Resonance, I am involved in the development of the SABRE technique for a wide variety of applications from the design of hyperpolarised contrast agents for magnetic resonance imaging (MRI) to process monitoring and control in industry using benchtop NMR.

I am also working on the development of a time-resolved NMR spectroscopy method using laser initiation and NMR detection with p-H2 hyperpolarisation. In contrast to conventional p-H2-enhanced experiments, where the addition of p-H2 occurs asynchronously and the reaction time is long on the timescale of the coherent evolution of the NMR signals, here we initiate the reaction with p-H2 photochemically using a 10 ns laser pulse. This coherent initiation step allows us to observe the build-up of parahydrogen hyperpolarisation on a microsecond timescale. The goal of this work is to develop a robust time-resolved NMR tool for measuring reactivity on micro-to-millisecond timescales. This project is a collaboration with the groups of Professor Simon Duckett and Professor Robin Perutz.

Time-resolved NMR spectroscopy with p-H2 hyperpolarisation

Time-resolved NMR spectroscopy with p-H2 hyperpolarisation

Selected publications

  • Macroscopic Nuclear Spin Diffusion Constants of Rotating Polycrystalline Solids from First-Principles Simulation.
    M E Halse, A Zagdoun, J-N Dumez  and L Emsley, Journal of Magnetic Resonance, 2015, 254, 48-55. 10.1016/j.jmr.2015.02.016
  • Direct observation of hierarchical protein dynamics.
    J R Lewandowski, M E Halse, M Blackledge and L Emsley, Science, 2015, 348, 578-58. 10.1126/science.aaa6111
  • Photochemical pump and NMR probe: Chemically created NMR coherence on a microsecond time scale.
    O Torres, B Procacci, M E Halse, R W Adams, D Blazina, S B Duckett, B Eguillor, R A Green, R N Perutz and D C Williamson, J. Am. Chem. Soc., 2014, 136, 10124- 0131. 10.1021/ja504732u
  • High-resolution 1H solid-state NMR spectroscopy using windowed LG4 homonuclear dipolar decoupling.
    M E Halse, J Schlagnitweit and L Emsley, Isr. J. Chem., 2014, 54, 134-146.
  • Improved phase-modulated homonuclear dipolar decoupling for solid-state NMR spectroscopy from symmetry considerations.
    M E Halse and L Emsley, J. Phys.Chem. A., 2013, 117, 5280-5290.
  • Quasi-equilibria in reduced Liouville spaces.
    M E Halse, J-N Dumez and L Emsley, J. Chem. Phys., 2012, 136, 224511.
  • A common theory for phase-modulated homonuclear decoupling in solid-state NMR.
    M E Halse, and L Emsley, Phys. Chem. Chem. Phys., 2012, 14. 9121-9130.
  • A first-principles description of proton-driven spin diffusion.
    J-N Dumez, M E Halse, M Butler and L Emsley, Phys. Chem. Chem. Phys., 2012, 14, 86-89.
  • Quantitative analysis of Earth's field NMR spectra of tightly coupled heteronuclei.Quantitative analysis of Earth's field NMR spectra of tightly coupled heteronuclei.
    M E Halse, P T Callaghan, B Feland and R E Wasylishen, J Magn. Reson., 2009, 200, 88-94.
  • A dynamic nuclear polarisation strategy for multidimensional Earth's field NMR spectroscopy.
    M E Halse and P T Callaghan, J. Magn. Reson., 2008, 195, 62-168.