Synthesis and Physicochemical Properties of Cryptophazane-A Soluble and Functionalizable C1-Symmetrical Cryptophane

The first example of a cryptophazane, a cryptophane functionalized with a nitrogen atom replacing one of the methylene bridges, is obtained with a 28 % overall yield over 8 steps, through the preparation of a C-1-symmetrical aza-cyclotriveratrylene (aza-CTV). Herein, we demonstrate that the introduction of a nitrogen atom on this part of the cryptophane core enhances the solubility in organic media of both the cryptophane and the synthetic intermediates, while presenting the same conformation as known cryptophanes. Cryptophazane was prepared on a multigram scale and easily functionalized. We also investigated its ability to encapsulate xenon atoms using hyperpolarized Xe-129 (HP Xe-129) NMR spectroscopy. We found that both its affinity and exchange kinetics were in the appropriate range for applications in Xe-129 magnetic resonance imaging (MRI). Combined with the wide range of possible functionalization, this makes cryptophazane an excellent candidate for targeted HP Xe-129 MRI.

Automated summary

The addition of a nitrogen atom to the cryptophane core enhances its solubility in organic solvents without changing its conformation. This new type of cryptophane has the potential for wide functionalization and shows promise in Xe-129 magnetic resonance imaging (MRI) applications.