Cryptophanes are a family of chiral molecular containers, characterized by their lipophilic internal cavity. The ability of cryptophanes to encapsulate hyperpolarized xenon has opened a great opportunity to develop highly sensitive ¹²⁹Xe-based MRI molecular tracers. A large number of ¹²⁹Xe-cryptophane biosensors have been developed for targeting various biological events. Although this concept is catchy, many challenges have been encountered, specifically in the elaboration of water soluble and easy functionalizable cryptophane derivatives.

The work presented in this thesis aims at developing a new straightforward approach to synthesize water soluble cryptophane sensors. These cages are based on cryptophane-[223] derivatives that bear a central carboxylic acid function to selectively graft a sensing unit, and six water soluble precursors on the cryptophanes’ rims. Using these platforms, three different water soluble sensors have been elaborated. These sensors have been characterized by ¹²⁹Xe NMR spectroscopy to assess their binding properties and responsiveness.

An additional aspect of these derivatives is their ability to undergo a solvent-dependent “self-encapsulation” phenomenon. This is characterized by the inclusion of the central functionality grafted on the propelendioxy linker towards the inner cavity of cryptophanes. This phenomenon has been clearly proved by ¹H NMR and IR spectroscopy. The effect on the overall chiroptical properties was also investigated by polarimetry, VCD and ECD spectroscopy.