Date of Award
Master of Science
PHIP (parahydrogen-induced polarization) refers to the family of approaches where the pure spin order from parahydrogen (pH2) is transferred to a molecular substrate. Whereas traditional PHIP involves hydrogenation of unsaturated bonds with pH2 to create the hyperpolarized agent, a comparatively new approach called SABRE (signal amplification by reversible exchange), pioneered by Duckett, Green, and co-workers, allows the spin order to be transferred from para-hydrogen without requiring permanent chemical change to the substrate. Instead, SABRE uses iridium-based catalysts to transiently bind both pH2 and the target substrate within the central Ir atom's ligand sphere. Much of this thesis will be concerning a technique dubbed SABRE-SHEATH (SABRE in Shield Enables Alignment Transfer to Heteronuclei) experiments where “home-built” para-hydrogen generators, sample reactors/“bubblers”, and magnetic shields are used to get the best NMR enhancements from heteronuclei like 15N. Indeed, to achieve hyperpolarization of the heteronuclear spins like 15N; the magnetic field must be ≤1 µT while pH2 is delivered to the sample. In collaboration with Warren Warren & Thomas Theis at Duke, it was recently shown at Vanderbilt that utilization of a simple magnetic shield during pH2 delivery to a sample can yield very large nuclear spin polarizations in 15N spins (up to 20% so far) of dilute species. This technique can be used to polarize bulk liquids as well. Here we report continuing explorations of this approach as a quick and extremely inexpensive way to generate bulk hyperpolarization and integration with cheap and simple home-built setups for pH2 generation and sample administration. Using our simple apparatus we were able to obtain a bulk ~700 fold enhancement of 15N signals from “neat” pyridine, enabling single-shot observation using the "standard" Ir SABRE catalyst ([lrCl (COD)(lMes)], (lMes = 1,3-bis (2,4,6-trimethylphenyl) imidazole-2-ylidene; COD = cyclooctadiene)]). The effects of sample composition—including the presence of deuterium spins—were also studied. The creation of a home built magnetic shield for SABRE-SHEATH with internal electromagnetic coils allowed the field within the shield to be optimized, and a first attempt at this effort is demonstrated. Up to ~ 400-fold enhancements were observed in 15N-labeled pyridine in deturated methanol, but significantly higher enhancements should still be possible. SABRE-SHEATH is arguably the “easiest gateway” for creating bulk hyperpolarization in heteronuclear spins. With the enhancement of imidazole, these methods could allow the simple creation of biologically relevant pH2 sensitive hyperpolarization agents at low financial and infrastructure costs. Ongoing efforts include optimization of the approach (to yield higher heteronuclear polarizations), and extending SABRE-SHEATH to aqueous and/or heterogeneous conditions. This thesis is organized as follows. Chapter 1 contains an introduction into the field of NMR, including topics relevant to nuclear spin hyperpolarization. Chapter 2 discusses hyperpolarization in more detail, with a particular focus on parahydrogen and traditional parahydrogen-induced polarization (PHIP). Chapter 3 introduces the newer form of PHIP called SABRE, with particular application towards the enhancement of 1H NMR signals under conditions of reversible exchange. Finally, Chapter 4 discusses experiments used to demonstrate and evaluate SABRE-SHEATH under various conditions using low-cost apparatus made from simple commercially available components. The chapter (and the thesis) concludes with a discussion of future directions of this work.
This thesis is only available for download to the SIUC community. Others should
contact the interlibrary loan department of your local library.