Cryptophane Derivatives as Gas Sensors and Hyperpolarized Xenon-129 Biosensors

ABSTRACT CRYPTOPHANE DERIVATIVES AS GAS SENSORS AND HYPERPOLARIZED XENON-129 BIOSENSORS Najat S. Khan Professor Ivan J. Dmochowski This thesis describes the progress in the development of cryptophanes for three different applications: encapsulation of noble gases, 129Xe NMR biosensing for cancer detection, and the construction of molecular devices. A new water-soluble organic host molecule, tris-(triazole ethylamine) cryptophane, was synthesized for noble gas detection. This host was found to bind xenon with the highest affinity to date (KA = 42,000 ± 2,000 M-1 at 293 K). The same host was employed in the development of a radiometric assay for measuring the association constant of radon binding to a discrete molecular species, KA = 49,000 ± 12,000 M-1 at 293 K. For cancer detection by hyperpolarized 129Xe MRI, a new folate-conjugated cryptophane biosensor was developed that targets folate receptors (FR) overexpressed in a majority of cancer cells. The biosensor was relatively non-toxic at low micromolar concentrations required for imaging and was shown to selectively target cancer cells overexpressing FR. Flow cytometry results indicated a 10-fold higher cellular internalization in KB cells (FR+) than in HT-1080 cells (FR-). Finally, a smaller cavity tribenzylamine hemicryptophane was synthesized where the molecular structure and motions of the cage closely resembled that of molecular gyroscopes. It also provided a vehicle for exploring the structure and properties of multiple p-phenylene rotators within one molecule. The compact size and molecular motions of this gyroscope-inspired tribenzylamine hemicryptophane make it an attractive starting point for controlling the direction and coupling of rotators within molecular systems