Development of 13C Liquid State Dynamic Nuclear Polarization at 9.4 TeslaDoctoral thesis
Date of Examination:2022-12-01
Date of issue:2023-07-11
Advisor:Prof. Dr. Marina Bennati
Referee:Prof. Dr. Marina Bennati
Referee:Prof. Dr. Christian Griesinger
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Format:PDFDescription:PhD Thesis Marcel Levien (no CV)
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EnglishThroughout the last decades, nuclear magnetic resonance (NMR) spectroscopy in liquids contributed to the structural elucidation of molecules of many types and sizes. Continuous improvements of the hardware and pulse sequences enabled the expansion of NMR applications from small molecules over large biological macromolecules to inorganic surfaces and battery research. However, the method is still hampered by the inherent low sensitivity arising from the small energy difference of the nuclear Zeeman states at magnetic fields employed in routine NMR experiments. One emerging approach to tackle the sensitivity issue is dynamic nuclear polarization (DNP), where spin polarization from highly polarized electron spins is transferred to nuclear spins. In order to push liquid state DNP forward on its journey to a viable option in the toolbox of routine NMR, two different avenues were pursued during the course of this thesis. Firstly, the influence of the molecular structure of the polarizing agent (PA) as well as rotational diffusion and fast structural rearrangements of the PA were investigated at low magnetic field. The goal was to derive favorable experimental conditions for 13C DNP at high magnetic field. The spin polarization transfer is favored, if the electron spin density of the PA is highly localized and readily accessible for the target molecule. Additionally, structural rearrangements of the PA that act on the picosecond to sub-picosecond timescale may amplify the DNP effect by modulating the hyperfine coupling on the correct timescale for DNP at high magnetic field. Secondly, a new DNP instrument operating at 9.4 T with a frequency agile gyrotron as a microwave source and a sample volume of up to 40 µL was developed. Large 13C NMR signal enhancements of up to 200 on model systems (e.g. CHCl3) and of up to 37 on a large variety of target molecules, including pharmaceutical drugs, were observed. The triple-resonance probehead was optimized to have an NMR resolution that is comparable with standard NMR experiments with linewidths in the range of 5-30 Hz and in favorable cases reaching 2.3 Hz. The collected results led to new mechanistic insights such as the efficient hyperpolarization of iodine containing compounds (enhancements of 10-33), possibly rooted in the halogen bond formation of the PA with iodine. The new DNP instrument also enabled DNP measurements in polar solvents, including water, with a sample volume of ~15 µL and an enhancement of up to 6. Finally, 2D DNP NMR was tested on 13C enriched and natural abundance target molecules and showed that the large signal enhancements of 1D NMR DNP are retained. This allowed for the transfer of the large hyperpolarization accumulated on favorable nuclear sites (e.g. iodinated carbons) to nuclei that cannot directly be polarized by DNP (e.g. fluorinated carbons or carbonyl groups) and therefore demonstrates the possibility to distribute the hyperpolarization over the target molecule.