Date of Award

12-1-2013

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Goodson, Boyd

Abstract

The ongoing effort to improve the sensitivity and information content of NMR spectroscopy and MRI has important implications in scientific research and medical diagnostics. In this dissertation, a variety of approaches have been investigated and expanded on in an effort to contribute to this field. First, cryptophanes are cage-shaped molecules that have previously been used to encapsulate molecules of interest for a number of potential applications--including gas sensing and biosensing. In one set of studies, encapsulation of molecular hydrogen gas (H2) has shown different behavior compared to other small organic molecules in C111 (up until now, the smallest cryptophane). The transient, non-covalent binding was studied by variable-temperature NMR at different fields up to 950 MHz. A mathematical model that considers multiple-H2 binding was developed to better understand the physics and binding process, with predictions compared to experimental data (and rationalized in light of quantum chemical calculations on possible H2@C111 complexes). To our knowledge, C111 is the only system to reversibly trap multiple H2 gas molecules non-covalently under mild conditions. In a second series of studies, the interaction of laser-polarized xenon and a water-soluble cryptophane was studied. Despite the low concentration of xenon in aqueous solution, it was possible to achieve polarization transfer from xenon to cryptophane spins via the SPINOE (spin-polarization induced nuclear Overhauser effect). The SPINOE enhancements, along with the 129Xe NMR spectra, provide information about the interaction of the Xe-cryptophane complex (variants of which are now used in so-called xenon biosensors). This was our first in-house successful application of hyperpolarized xenon as a signal source for the spins of other molecules, leading the way to a number of ongoing studies. Although the absolute NMR enhancements obtained via the SPINOE were small, much larger enhancements were studied in a technique that uses para-hydrogen (pH2)--a spin isomer of normal molecular hydrogen)--as the source of spin order. As with the xenon experiments (and the H2 binding experiments), pH2 must be delivered as a gas to a sealed sample prior to performing the NMR experiments. Parahydrogen-induced polarization (PHIP) is an emerging field in enhancing the sensitivity in NMR experiments and may play an important role in MRI studies. Within this field a very recent phenomena of signal amplification by reversible exchange (SABRE) was investigated. The reproducibility of this recent discovery has been examined and new conclusions about the mechanism of this technique are delineated. NMR signal enhancements of nearly ~400-fold are reported. Moreover, a new water soluble NHC-Iridium catalyst was synthesized and investigated in SABRE related studies. We also report the first studies of SABRE-enhancement in biologically tolerable solvents--opening a door to the development of SABRE-hyperpolarized metabolic contrast agents for subsecond molecular imaging in the body. Although much of the above work was motivated by the desire to improve NMR/MRI sensitivity enhancement, other efforts concerned the other side of the equation--improving NMR/MRI information content. The next section concerns our efforts to investigate use of Variable-Angle (VA) NMR to study composite liquid crystal (LC) media comprised of stretched polyacrylamide gels (SAG) and embedded bacteriophage Pf1 particles. This in situ combination exploited the apparent interference between the different solute-aligning properties of the two LC components--yielding composite media with alignment properties that can differ in a tunable manner from those obtained with each medium alone. Characterization of alignment of both large and small molecules provides more insight into the nature of solute alignment that those composite phases introduce--with the goal of developing this approach as a new technique for studying molecular structure and dynamics via the dipolar and quadrupolar couplings that are restored in liquid-crystalline media. Finally the use of SPIONS--superparamagnetic iron oxide nanoparticles--as contrast agents is a relatively new approach to enhance information content in MRI studies; this is particularly true for SPIONs that have been surface-functionalized to achieve an environment-sensitive MR response. Novel surface-functionalized SPIONs were investigated by examining their effect on nuclear spin relaxation in aqueous environments simulating bodily tissues. More specifically, the pH and ionic strength dependent properties of selected dendron-functionalized and polymer-functionalized SPIONs have been examined. Of particular interest to this dissertation is how environment-mediated transient clustering of the SPIONs gives rise to changes in so-called transverse (homogeneous) spin relaxation rates as measured by following the decay of MR signals detected after the application of a series of radio-frequency (RF) pulses. In order to better understand these effects in the context of the SPIONs' behavior, a mathematical model is under development whose predictions are compared with experimental data. Aspects of the model are also compared to transmission electron micrography (TEM) and dynamic light scattering (DLS).

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