Date of Award
6-27-2025
Date Published
August 2025
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
Advisor(s)
John Franck
Second Advisor
Paul Souder
Subject Categories
Chemistry | Physical Sciences and Mathematics
Abstract
Overhauser Dynamic Nuclear Polarization (ODNP) analyzes the translational dynamics of hydration water surrounding macromolecules as well as water in confined or tight porous environments. It requires instrumentation comprising an Nuclear Magnetic Resonance (NMR) spectrometer, an Electron Spin Resonance (ESR) spectrometer, as well as a microwave power source that are not currently available as an integrated commercial system. It analyzes the translational motion of water passing through the magnetic field generated by a spin label, which lasts for tens to hundreds of picoseconds. ODNP most sensitively detects these motions when the magnetic field is chosen such that the ESR resonance frequency matches the inverse of this time scale. Thus, ODNP requires NMR at low magnetic fields – e.g., fields near 0.35 T that correspond to an ESR resonance frequency of 9.8 GHz. Unfortunately, low-field Magnetic Resonance (MR) suffers from inhomogeneities and low signal-to-noise ratio (SNR), both of which challenge the precision of the method. Here, we discuss how modern object-oriented libraries open up new opportunities in MR data analysis. Specifically, client-server metadata logging software can organize the data from modular instrumentation, such as the custom ODNP system here, that acquires relatively complicated datasets. Meanwhile, we develop software to automate the production of figures that map out signal arising from various quantum coherence pathways (using the Domain-Colored Coherence Transfer (DCCT) schema introduced in an earlier publication). Subsequently, a new modern perspective clarifies the most important principles of NMR sensitivity. In particular, it finds that a real-time signal filtration on the one hand proves crucial for low-field signal acquisition but, on the other hand, obstructs the diagnosis and mitigation of interference noise. This modern perspective leads to a protocol for identifying and tracking noise, starting from a broad spectrum view and zooming in to the narrow bandwidths that allow digitisation of seconds-long signal decays, ultimately enabling a significant improvement in sensitivity. After it proves its validity by predicting the signal voltages observed for ODNP experiments on capillary-tube-sized samples, it also predicts a path for instrument redesign that will lead to future gains in sensitivity through NMR probe redesign. Finally, a detailed analysis of the quantification of NMR signal and the prediction of the associated error further refines the sensitivity of the ODNP experiment, enabling studies at lower concentrations. Accompanying these advances, a simple and practicable technique for quantifying spin probe stocks based on their lineshapes is demonstrated. Overall, this thesis presents a collection of crystallized, quantitative understanding of experimental signal and noise in low field, magnetic resonance, as well as a concommitant set of practical strategies that will enable the deployment of high sensitivity ODNP measurements into a larger variety of laboratories. Furthermore, it sets the stage for pushing the threshold to even lower fields, enabling the exploration of even slower translational motions.
Access
Open Access
Recommended Citation
Guinness, Alexandria, "Advancing the Sensitivity and Precision of Overhauser Dynamic Nuclear Polarization with a Foundation in the First Principles of Nuclear Magnetic Resonance Physics" (2025). Dissertations - ALL. 2149.
https://surface.syr.edu/etd/2149
