In this study, the groups of Prof. Gilles Gasser at the Institute of Chemistry for Life and Health Sciences at Chimie ParisTech-PSL and of Prof. Matthieu Sollogoub at Sorbonne Université show that a cyclodextrin(CD)-encapsulated copper(I) catalyst is capable of activating a fluorophore inside living cells whilst displaying no cytotoxicty.

The copper(I) catalysts used in this work are N-heterocyclic carbene (NHC)-copper(I) complexes which are otherwise extremely cytotoxic without encapsulation. The copper-catalyzed activation of fluorescein was achieved in cancer cells by using a pro-fluorescein derivative, protected by pinacol boronic ester groups (FBBBE) It was demonstrated that the fluorophore deprotection is accelerated in the presence of the catalyst.

The variety of copper ligands used for catalysis with cells is very limited and there is no example with NHC ligands which represent a major family of ligands in catalysis. This study establishes for the first time that the encapsulation within a cyclodextrin cavity dramatically reduces the toxicity of an NHC-copper(I) complex whilst maintaining a catalytical activity, which can take place inside a living organism. This breakthrough is a strong incentive for the use of encapsulation strategies to protect the metal centres from natural chelators and reduce their innate toxicity while keeping a catalytical activity. Furthermore, the encapsulating structure can be used as a support to bind targeting moieties, allowing for the specific delivery of the active metal centre. This can have applications in cellular imaging or co-localisation studies and eventually could be considered for in situ pro-drug activation.

This article has just been accepted in Chemical Science.
It can be freely downloaded here.