Synthetic Optimization of Organic Radicals for Dynamic Nuclear Polarization

Massachusetts Institute Of Technology, Cambridge MA

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Abstract

DESCRIPTION (provided by applicant): Nuclear magnetic resonance (NMR) spectroscopy is uniquely suited to provide information about the structure and dynamics of non-crystalline materials; these include biologically relevant materials like non-crystalline proteins, membrane-bound proteins, amyloids, peptides, micelles and vesicles. Consequently, this technique promises to shed light on a number of pathological processes implicated in diseases including diabetes, Alzheimer's and Parkinson's, among many others. Because these NMR techniques generally involve observation of low-gamma nuclei with low equilibrium polarization, however, sensitivity in the NMR experiment is inherently low and experiments must be arduously long. A number of means to increase nuclear sensitivity in NMR experiments have been discovered, but perhaps the most generally applicable method is microwave-driven dynamic nuclear polarization (DNP). In a DNP-enhanced NMR experiment, mixtures of stable organic radicals and a molecule of interest are irradiated at particular microwave frequencies. The irradiation causes polarization to be transferred from the radical electrons-which are naturally more polarized-to the less polarized nuclei, resulting in enhanced NMR signal intensity. Until recently, DNP experiments have made use of conventional stable organic radicals as a source of polarized electrons. Because these radicals are not specifically designed for use in the DNP process, signal enhancements fall short of the theoretical maximum values. This proposal aims to improve overall signal enhancement in DNP experiments by design and synthesis of radicals specifically tailored for use as DNP agents. The strategies proposed include: 1) tuning radical electron g-values to precisely match the conditions ideal for the operative DNP mechanisms. This will be accomplished by incorporating heavy atoms and transition metals into the electronic structure of known radical DNP agents; 2) optimizing the electron spin-lattice relaxation times in order to reduce the necessary build-up time for nuclear polarization. This can be achieved by functionalizing the peripheral components of the radicals; and 3) maximizing electron-electron dipolar coupling while simultaneously minimizing exchange coupling to further increase polarization. Optimizing couplings will require assaying a number of potential linking units binding two radicals. Organic and inorganic synthetic methods will provide access to the proposed radicals, and detailed investigation of the electronic and magnetic properties of the synthesized radicals will inform further design. Success with any of these strategies stands to improve enhancement factors of DNP agents, thus rendering advanced NMR techniques more amenable for the investigation of crucial human health issues.