β-Carboline platform-based novel fluorescent probes for the selective detection of zinc ions: synthesis, live-cell imaging and computational studies

Abstract

The imbalance of zinc ions (Zn²⁺) in the body can lead to abnormal cellular states. Therefore, visualization and tracking of Zn²⁺ in biological systems are highly desirable. Despite the availability of numerous photoinduced electron transfer (PET) Zn²⁺ sensors, many of them suffer from poor Zn²⁺ selectivity/and or cumbersome synthetic protocols. Herein, we report the design and synthesis of β-carboline platform-based fluorescent probes (CS1–CS3) for the detection of Zn²⁺ in aqueous solution and living cells. The coordination sphere of these probes, featuring three fixed borderline basic binding nitrogen functions along with varying coordinating groups, yielded an optimum coordination geometry for enhanced Zn²⁺ selectivity. These probes exhibited higher Zn²⁺ selectivity over a range of competing metal ions, with a limit of detection between 0.38 nM to 4.5 nM. The working principle was based on the PET mechanism, wherein the addition of Zn²⁺ to the solutions of CS1–CS3 resulted in 5.0-fold, 6.5-fold, and 14.6-fold fluorescence enhancements, respectively, accompanied by concomitant color changes from blue to bright cyan. DFT calculations revealed that these probes formed thermodynamically stable penta-coordinate probes/Zn²⁺ complexes of trigonal bipyramidal geometries, with CS3/Zn²⁺ displaying the highest stability. Moreover, the formation of probes/Zn²⁺ complexes was also verified by ¹H-NMR spectroscopy, wherein distinct changes in the spectra of free and probe/Zn²⁺ complexes were observed. In addition, these probes exhibited low toxicity and a reversible fluorescence switching response, and were applied to monitor Zn²⁺ in WiDr cells. Thus, these probes hold great promise for selective detection of Zn²⁺ in biological systems and the environment.