Symmetrical bis-salophen probe serves as a selectively and sensitively fluorescent switch of gallium ions in living cells and zebrafish

Abstract The semi-metallic element gallium has repeatedly shown bio-activities in preclinical and clinical studies. Gallium derivatives have already entered clinical trials for treatment of various refractory malignancies. To better monitor or track the status of administered gallium compound, herein a novel fluorescent probe N,N',N'',N'''-Tetrakis(2-hydroxybenzylidene)biphenyl-3,3',4,4'-tetramine (bis-salophen) has been designed and synthesized. The bis-salophen probe was found to recognize gallium ions (Ga3+) with high selectivity and sensitivity over other cations via fluorescence “turn on” strategy. The spectroscopy results exhibited a 1:2 stoichiometry for probe and Ga3+, and the association constant and limit of detection were calculated as 8.85 × 106 M−1 and 13.0 nM, respectively. Additionally, base on spectroscopy and theoretical research, the mechanism of Ga3+ sensing action was explored by density functional theory (DFT), which indicated suppression of photoinduced electron transfer (PET) action along with the interruption of π-conjugation between salicylaldehyde and 3,3-diaminobenzidine backbone by Ga3+ ions. Furthermore, the biological applicability of bis-salophen probe were evaluated in various normal and cancer cell lines, results have shown that this probe is highly selective and sensitive for cancer cells. Finally, zebrafish imaging confirmed and indicated that the probe is also capable of examining Ga3+ ions. Collectively, these results suggest that we have successfully developed a novel probe for selective and sensitive detection of Ga3+ ions both in living cells and zebrafish. We expect that our work here will shed light on future development of Ga3+ detecting probes and wider application in the filed of biology and medicine shall be anticipated.