Date of Award
Doctor of Philosophy (PhD)
The application of dynamic nuclear polarization (DNP) and magic angle spinning (MAS) significantly improves the sensitivity of solid state nuclear magnetic resonance (NMR), making it a suitable tool to investigate structures and dynamics of complex biological systems. This dissertation describes the development of instrumentation and methods in various aspects with the goal of achieving time-domain and in-cell DNP NMR. In-cell NMR is necessary for obtaining functional structures and dynamics of proteins and interacting ligands in the native environment. Time-domain DNP could circumvent the cryogenic temperature restriction and permit DNP experiments at physiological temperatures, which is important for characterizing accurate in-cell conformations. This work describes a novel targeting, cell-penetrating, and fluorescent polarizing agent that was developed as a first step toward DNP inside living cells. High MAS frequencies, which can yield high spectral resolution, are exploited by designing and implementing spherical NMR rotors. Other strategies to improve DNP enhancement were also investigated, including the development of the frequency-agile, high-power gyrotron, which allows implementation of time-domain DNP and produce enhancement gain utilizing frequency-chirped microwave pulses. Lastly, the microwave simulation of MAS microwave resonators is presented, showing a high Q factor and drastically improved electron Rabi frequency, which could mitigate the limiting factor for time-domain DNP performance at high magnetic fields.
Chair and Committee
Alexander B. Barnes Sophia Hayes
Alexander B. Barnes, Sophia E. Hayes, Meredith Jackrel, Joseph A. Fournier,
Gao, Chukun, "Instrumentation and Methods for Time-domain and In-cell Dynamic Nuclear Polarization" (2019). Arts & Sciences Electronic Theses and Dissertations. 2001.
Available for download on Friday, December 15, 2119