Date of Award

Summer 8-12-2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Dr. Ivan J. Dmochowski

Second Advisor

Dr. Virgil Percec

Third Advisor

Dr. David Christianson, Dr. Bill Dailey

Abstract

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.

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