Chemoselective Alteration of Fluorophore Scaffolds as a Strategy for the Development of Ratiometric Chemodosimeters

Abstract

Ratiometric sensors generally couple binding events or chemical reactions at a distal site to changes in the fluorescence of a core fluorophore scaffold. However, such approaches are often hindered by spectral overlap of the product and reactant species. We provide a strategy to design ratiometric sensors that display dramatic spectral shifts by leveraging the chemoselective reactivity of novel functional groups inserted within fluorophore scaffolds. As a proof-of-principle, fluorophores containing a borinate (RF₆₂₀ ) or silanediol (SiOH2R) functionality at the bridging position of the xanthene ring system are developed as endogenous H₂ O₂ sensors. Both these fluorophores display far-red to near-infrared excitation and emission prior to reaction. Upon oxidation by H₂ O₂ both sensors are chemically converted to tetramethylrhodamine, producing significant (≥66 nm) blue-shifts in excitation and emission maxima. This work provides a new concept for the development of ratiometric probes.

Keywords: bioorthogonal reaction; fluorescent probes; reactive oxygen species; sensors; signal transduction.