Encapsulating NHC‐capped Copper(I) Complexes inside Cyclodextrin for Catalysis in Living Cells

Abstract

The development of "non-natural" chemical reactions inside living organisms is an expanding field of research. In this area, metal-based catalysis has been particularly scrutinised. However, most examples of catalysts developed so far are based on expensive and rare heavy metals such as ruthenium, iridium or palladium. For this reason, the development of catalysis in cells or in vivo with more accessible first-row metals is of great interest and could significantly increase the catalogue of reactions applicable in these complex environments. Herein, we demonstrate that encapsulating copper(I) N-heterocyclic carbene (NHC) catalysts inside the cavity of modified cyclodextrins, renders these notoriously toxic complexes harmless towards CT26 cells at high concentrations. Nevertheless, the catalytic activity of cyclodextrin(CD)-encapsulated NHC-copper complexes is preserved, allowing the deprotection of pinacol boronate ester groups outside and inside living cells to release phenol-based fluorophores. In cells, the production of fluorophore in the presence of CD-NHC-copper catalysts outperforms that induced by the cellular machinery alone and endogeneous ROS.