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

• Published in: Chemistry : a European journal 2004-06, Vol.10 (12), p.3015-3025
• Main Authors: Henary, Maged M., Wu, Yonggang, Fahrni, Christoph J.
• Format: Article
• Language: English
• Subjects: fluorescent probes; ligand design; proton transfer; sensors; zinc
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200305299

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 ZnII at neutral pH, the fluorophores undergo ESIPT to yield a highly Stokes' shifted emission from the proton‐transfer tautomer. Coordination of ZnII inhibits the ESIPT process and yields a significant hypsochromic shift of the fluorescence emission maximum. Whereas the paramagnetic metal cations CuII, FeII, NiII, CoII, and MnII result in fluorescence quenching, the emission response is not altered by millimolar concentrations of CaII or MgII, rendering the sensors selective for ZnII among all biologically important metal cations. Due to the modular architecture of the fluorophore, the ZnII binding affinity can be readily tuned by implementing simple structural modifications. The synthesized probes are suitable to gauge free ZnII concentrations in the micromolar to picomolar range under physiological conditions. Biological zinc detector: A set of emission ratiometric fluorescent zinc(II) sensors (right of figure) have been developed, which utilize the inhibition of excited‐state intramolecular proton transfer (ESIPT) to provide large hypsochromic shifts upon ZnII coordination (left of figure). The sensors cover a wide range of binding affinities and are suitable to gauge free ZnII concentrations in the micromolar to picomolar range under physiological conditions.