Push–pull dioxaborine as fluorescent molecular rotor: far-red fluorogenic probe for ligand–receptor interactions

Abstract

Fluorescent solvatochromic dyes and molecular rotors have attracted considerable attention as fluorogenic probes because of background-free detection of biomolecules in live cells in no-wash conditions. Herein, we introduce a push–pull boron-containing (dioxaborine) dye that presents unique spectroscopic behavior combining solvatochromism and molecular rotor properties. Indeed, in organic solvents, it shows strong red shifts in the absorption and fluorescence spectra upon increase in solvent polarity, which is typical for push–pull dyes. On the other hand, in polar solvents, where it probably undergoes twisted intramolecular charge transfer (TICT), the dye displays strong dependence of its quantum yield on solvent viscosity, in accordance with the Förster–Hoffmann equation. In comparison to solvatochromic and molecular rotor dyes, the dioxaborine derivative shows an exceptional extinction coefficient (120 000 M⁻¹ cm⁻¹), high fluorescence quantum yields and a red/far-red operating spectral range. It also displays much higher photostability in apolar media as compared to Nile Red, a fluorogenic dye of similar color. Its reactive carboxyl derivative has been successfully grafted to carbetocin, a ligand of the oxytocin G protein-coupled receptor. This conjugate exhibits a >1000-fold turn on between apolar 1,4-dioxane and water. It targets specifically the oxytocin receptor at the cell surface, which enables receptor imaging with excellent signal-to-background ratio (>130). We believe that the presented push–pull dioxaborine dye opens a new page in the development of fluorogenic probes for bioimaging applications.