Synthesis of new cryptophanes: toward xenon-MRI biosensor and beyond – Neo-Crypto

Cryptophanes (Crs) are cage-like host molecules composed of two molecular crowns, cyclotriveratrylene (CTV) units usually connected by three ether linkers. These molecular hosts are known since decades to be able to encapsulate many different entities, in particular they are well suited for xenon. Then, the development of Cr-based biosensors has been tremendously studied for applications in hyperpolarized xenon magnetic resonance imaging (MRI) in biological systems. Several works have demonstrated their applicability and relevance, in particular in cells assays, but to date, no application of such a bioprobe has been reported in vivo. Indeed, the complex preparation of Cr-monosubstituted derivatives and the poor solubility of these molecules in biocompatible media precludes the obtention of an efficient xenon based bioprobe. Nevertheless, over the past four decades, considerable progress has been made in the characterization of the cryptophane’s structural aspects and exploration of their unique host–guest chemistry, in both organic and aqueous solutions. However, the synthetic schemes to produce such derivatives have not evolved so much, leading to minor modifications of the whole backbone of cryptophanes, then narrowing their potential others applications. The purpose of Neo-Crypto project is to extend the cryptophane chemical space by using and improving a newly described synthetic strategy. The obtained new molecular hosts will be evaluated as hyperpolarized Xe-sensors for MRI. Other physicochemical properties will also be evaluated through collaborations: radon complexation and chiroptical properties.