Synthesis of functionalized cryptophane-A derivatives and assessment of their xenon-binding properties for the construction of hyperpolarized xenon-129 biosensors

This dissertation describes the progress in the synthesis and physical studies of cryptophane-A derivatives for use in the construction of hyperpolarized xenon-129 biosensors. Access to functionalized xenon-129 biosensors has been improved through the development of propargyl substituted cryptophanes to allow for the conjugation of bioactive moieties using the click reaction. New water-soluble cryptophane-A derivatives TAAC and TTPC have been synthesized and subjected to precise measurement of their xenon-binding affinity. These xenon binding constant determinations were made possible through the development of solution-phase xenon handling techniques which allowed access to xenon fluorescence quenching and isothermal titration calorimetry (ITC) assays. The insights gained from these studies have led the way towards an improved synthetic route to functionalizable cryptophanes and a proposed method to systematically vary the chemical shift of encapsulated xenon-129 without sacrificing xenon binding affinity. Finally, access to tri-allyl cryptophane 3.4 has allowed for crystallographic studies of cryptophane conformation as well as the interaction of xenon and other guest molecules with the cryptophane interior