Development and Validation of a Fluorogenic Probe for Lysosomal Zinc Release

Zinc homeostasis, which allows optimal zinc utilization in diverse life processes, is responsible for the general well-being of human beings. This paper describes developing and validating an easily accessible indole-containing zinc-specific probe in the cellular milieu. The probe was synthesized from readily available starting materials and was subjected to steady-state fluorescence studies. It showed selective sensing behavior towards Zn2+ with reversible binding. The suppression of PET (Photoinduced Electron Transfer) and ESIPT (Excited State Intramolecular Proton Transfer) elicited selectivity, and the detection limit was 0.63 mu M (LOQ 6.8 mu M). The zinc sensing capability of the probe was also screened in the presence of low molecular weight ligands [LMWLs] and showed interference only with GSH and ATP. It is non-toxic and can detect zinc in different cell lines under various stress conditions such as inflammation, hyperglycemia, and apoptosis. The probe could stain the early and late stages of apoptosis in PAN-2 cells by monitoring the zinc release. Most experiments were conducted without external zinc supplementation, showing its innate ability to detect zinc. This paper describes the application of an indole-based probe for selective zinc sensing via suppression of PET and ESIPT processes. The probe is non-toxic and can detect lysosomal zinc in various cell lines without external zinc supplementation. It is also capable of staining the early and late stages of apoptosis in PAN-2 cells by tracking the zinc release.image