A reversible fluorescence chemosensor for sequentially quantitative monitoring copper and sulfide in living cells

•FL is a renewable fluorescent chemosensor for the sequential detection of Cu2+ and S2−.•FL exhibits low cytotoxicity and cell-membrane permeability.•The fluorescence imaging and quantification of Cu2+ and S2− in living cells were achieved.

We report a novel, selective and sensitive strategy for the sequentially “ON–OFF–ON” fluorescent detection of Cu2+ and S2− based on a fluorescein derivative, FL. The specific binding of FL towards Cu2+ in aqueous and biological media led to the intensive green fluorescence quenching and a notable increase of the absorbance maximum at 480 nm. In the presence of S2−, the intensity and overall pattern of the fluorescence emission and UV–vis spectra of FL–Cu2+ ensemble were recovered since the abolishment of paramagnetic Cu2+. This displacement approach exhibited highly specificity, and sensitivity with detection limits of 3 nM for Cu2+ and 150 nM for S2−. The fluorescence “ON–OFF–ON” circle can be repeated to a minimum of 5 times by the alternative addition of Cu2+ and S2−, implying that FL is a renewable dual-functional chemosensor. The biocompatibility of FL toward breast carcinoma cells, MDA-MB-231 was confirmed by MTT assay. The reversible “ON–OFF–ON” fluorescent response of FL to Cu2+ and S2− in living system was further confirmed by confocal fluorescence imaging of living cells. The quantification of Cu2+ and S2− in single intact cell was realized by the flow cytometry analysis.

Graphical abstractBioactive ions as well as molecules play fundamental roles in a wide spectrum of biological processes. The desirable features of proposed chemosensor, FL, such as high sensitivity, working well at physiological pH, high specificity, reversibility and low toxicity insured the application for sequential quantification of Cu2+ and S2− in living cells. This work has opened a way to explore the roles of Cu2+ and S2− plays in biological system, as well as provide a strategy to develop reversible chemosensor for quantification the intracellular reactive species, including ions and small molecules.Figure optionsDownload full-size imageDownload as PowerPoint slide