Zinc(II)-Selective Ratiometric Fluorescent Sensors Based on Inhibition of Excited-State Intramolecular Proton Transfer

Abstract

To develop a zinc(II)-selective emission ratiometric probe suitable for biological applications, we explored the cation-induced inhibition of excited-state intramolecular proton transfer (ESIPT) with a series of 2-(2′-benzenesulfonamidophenyl)benzimidazole derivatives. In the absence of Zn^II at neutral pH, the fluorophores undergo ESIPT to yield a highly Stokes' shifted emission from the proton-transfer tautomer. Coordination of Zn^II inhibits the ESIPT process and yields a significant hypsochromic shift of the fluorescence emission maximum. Whereas the paramagnetic metal cations Cu^II, Fe^II, Ni^II, Co^II, and Mn^II result in fluorescence quenching, the emission response is not altered by millimolar concentrations of Ca^II or Mg^II, rendering the sensors selective for Zn^II among all biologically important metal cations. Due to the modular architecture of the fluorophore, the Zn^II binding affinity can be readily tuned by implementing simple structural modifications. The synthesized probes are suitable to gauge free Zn^II concentrations in the micromolar to picomolar range under physiological conditions.