The synthesis and optimization of cryptophane cages for use in xenon bio-imaging
Problems plaguing current imaging techniques such as X-ray, nuclear and magnetic resonance imaging (1H MRI), has led to the development of a new imaging method. X-ray imaging is incapable of imaging anything beyond anatomy, whilst nuclear imaging utilizes radioactive isotopes. 1H MRI is not as sensitive as nuclear imaging and it suffers from a lack of contrast due to high background signals from the massive amounts of protons in the body. Herin, we report the synthesis of cryptophane cages that can bind xenon atoms, and the use xenon-129 to obtain a signal used in for magnetic resonance imaging. ^ The cryptophane cages' ability to bind 129Xe depends on the size of the cryptophane cavity. We have synthesized cryptophanes of different cavity sizes by utilizing linkers of varying lengths. We also functionalized the cryptophane cages via Huigsen cycloaddition, resulting in water soluble cryptophanes at pH > 8. We developed water soluble cages of different cavity sizes as well as of varying degree of solubility. We also developed a tri-hydroxy cryptophane cage that can be readily functionalized. The 129Xe-NMR spectra showed an encapsulated peak for the [2,2,2] cryptophane cage in DMSO; however, the encapsulated xenon peak proved elusive in larger cavity cryptophanes and water soluble cryptophanes. Diffusion, low xenon solubility in water and increased xenon exchange rates hindered the detection of the encapsulated 129Xe peak. The Hyperpolarized Chemical Exchange Saturation Transfer (Hyper-CEST) technique will need to be employed in order to develop a robust imaging technique with these cages. ^ The chemical shift of 129Xe is a function of its chemical environment. Fluctuations in pH, solvent and molecular substituents have all been shown to affect the chemical shift of 129Xe. We sought to detect the effects of temperature fluctuations have on the 129Xe chemical shift. Utilizing corn oil and saline solution as our solvents, the chemical shift of 129Xe in corn oil was seen to increase linearly with temperature increase, whilst no observable trend was seen in saline solution. Discovery of this paves the way for a new temperature measurement of deep tissue without the use of invasive techniques.^
Chemistry, Biochemistry|Chemistry, Organic
"The synthesis and optimization of cryptophane cages for use in xenon bio-imaging"
Dissertations and Master's Theses (Campus Access).