Synthesis of Cryptophanes with Two Different Reaction Sites: Chemical Platforms for Xenon Biosensing

Abstract

We report the synthesis of new water-soluble cryptophane host molecules that can be used for the preparation of (129)Xe NMR-based biosensors. We show that the cryptophane-223 skeleton can be modified to introduce a unique secondary alcohol to the propylenedioxy linker. This chemical functionality can then be exploited to introduce a functional group that is different from the six chemical groups attached to the aromatic rings. In this approach, the generation of a statistical mixture when trying to selectively functionalize a symmetrical host molecule is eliminated, which enables the efficient large-scale production of new cryptophanes that can be used as chemical platforms ready to use for the preparation of xenon biosensors. To illustrate this approach, two molecular platforms have been prepared, and the ability of these new derivatives to bind xenon has been investigated.

Fully Collapsed Imploded Cryptophanes in Solution and in the Solid State

“…The typical structure has a crown‐crown (CC) out‐out conformation in which the two upper rims the CTBs face one another, Scheme . There are a handful of reported examples of out – saddle conformation, which is observed in those cases in which one crown has undergone pseudo‐rotation to the twisted saddle form giving a partially “imploded” crown‐saddle (CS) structure, Scheme . The out ‐ saddle conformation of imploded cryptophanes was first unequivocally demonstrated by Holman and co‐workers with a crystal structure of a m ‐xylyl‐linked anti cryptophane, and there has been one further crystal structure of an imploded cryptophane with triallyl decoration from Dmochowski and co‐workers .…”

“…However, the out‐in CC form of cryptophane‐E is at least 29 kJ mol −1 higher in energy . Formation of imploded cryptophanes is generally attributed to partial collapse of the initially synthesised out‐out cage structure on removal of included guest molecules, achieved by high temperature evacuation or heating the cage in a solvent that is too large to occupy the cage cavity . An exception to this was reported by Berthault and co‐workers, who observed spontaneous isomerisation of a water‐soluble cryptophane to the out ‐ saddle form in degassed aqueous solution .…”

A Straightforward Access to Cyclotriveratrylene Analogues with C1 Symmetry: Toward the Synthesis of Monofunctionalizable Cryptophanes

“…In this context, there is an urgent and unmet need to develop straightforward synthetic methods leading to simultaneously hydrophilic and C 1 ‐symmetric cryptophane congeners. Recently, two water‐soluble cryptophanes bearing a single functionality on their skeleton were reported by Brotin and co‐workers . In this work we synthesized one such cryptophane from the C 1 ‐symmetric CTV 2 that contains three poly(ethylene glycol) (PEG) chains as water‐soluble moieties.…”

Chiroptical study of cryptophanes subjected to self‐encapsulation

“…We have recently reported the synthesis of new cryptophane‐223 scaffolds for xenon complexation that contain two orthogonal reactive functions . Among the different prepared host molecules, a cryptophane derivative bearing seven acetate moieties (compound 1 in Scheme ) has attracted our attention, since its 129 Xe NMR spectrum shows an unusual broad signal in 1,1,2,2‐tetrachloroethane‐ d 2 .…”