Fluorescent Cu2+ sensor based on phenanthroline-BODIPY conjugate: A mechanistic study

Abstract

Development of a specific Cu2+ sensor for the detection of labile Cu2+ ions in vivo in the presence of labile pools of other biologically important metal ions is a real challenge due to similar binding affinity of these metal ions with the ligands containing N and O donor atoms. Here, we designed and synthesized a mixed N- and O-donor atoms containing BODIPY-phenanthroline conjugate where two BODIPY dyes are linked at 2 and 9 position of 1,10-phenanthroline moiety through amide linkage. NMR and X-ray crystallography studies were done to characterize the dye structure. Phenanthroline is a known binder of different metal ions without much selectivity, but the new ligand shows highly selective detection of Cu2+ ions via fluorescent turn off mechanism without any interference with other biologically important metal ions. The sensing mechanism was investigated by detailed photochemical, electrochemical, NMR, FTIR, MALDI-TOF and DFT studies. The BODIPY-phenanthroline conjugate forms 1:1 complex with the Cu2+ ion which is confirmed by NMR, MS and DFT studies. Importantly, both dynamic and static quenching processes are responsible for the fluorescence attenuation of the BODIPY-phenanthroline conjugate in the presence of Cu2+ ions. The new ligand is cell-permeable and non-toxic to the cells under tested concentrations. Finally, its potential application to monitor cellular accumulation of Cu2+ ions and detection of Cu2+ in serum samples are also investigated and discussed.