Transposing molecular fluorescent switches into the Near-IR: Development of luminogenic reporter substrates for redox metabolism

This study reports the development of a Nd(III)-based near-IR luminescent probe for monitoring aldo-ketoreductase (AKR) enzyme activity. We have adapted a coumarin-based reporter substrate for the AKR1C2 to a near-IR emitting format by tethering the former to a macrocyclic Nd(III) moiety via an alkyl linker. Enzymatic reduction of the ketone functionality on the coumarin alters the energy transfer efficiency from the fluorophore to the emitting lanthanide species, resulting in emission at similar to 1060 nm from the alcohol product. The efficiency of sensitization is not significantly affected by extending the alkyl tether from two to three carbons, and even a six-carbon linker still supports viable sensitized luminescence. In addition, the suitability of these complexes to act as enzyme substrates improves with longer linker length. We have thus developed long wavelength luminogenic reporter substrates for a redox enzyme and also a general platform for transposing molecular fluorescence into the more desirable near-IR region.