The design of β-carboline–8-aminoquinoline tethered probes for nanomolar Zn²⁺ sensing and cell imaging

Maintaining optimal Zn²⁺ concentrations are essential for various physiological and environmental systems. Despite many reported Zn²⁺ sensors, their selectivity and operational simplicity often remain inadequate. In this work, two newly engineered β-carboline–derived fluorescent probes ( S1 and S2 ) are presented as efficient and sensitive Zn²⁺ recognition platforms. The probes integrate 8-aminoquinoline with a β-carboline framework to form half-ring confined binding cavities that enable selective Zn²⁺ coordination. These probes can selectively detect Zn²⁺ with fluorescence enhancement upon binding with Zn²⁺, due to PET suppression mechanism, yielding strong signal amplification and nanomolar-level detection with limit of detection of 1.3 nM and 2.2 nM, respectively. DFT analyses suggested hexacoordinate geometries with square bipyramidal arrangements for Zn²⁺–probe complexes with favourable thermodynamic stability. Moreover, ¹H NMR spectra provided evidence for the formation of probe/Zn²⁺ complexes, as distinct changes were observed between the free probe and the complexed form. The probes also demonstrate high biocompatibility, reversible fluorescence modulation, and successfully applied to monitor Zn²⁺ in WiDr cells that validate their potential for Zn²⁺ imaging in cellular environments.