Polypyridyl substituted BODIPY derivatives; water switchable imaging probes that exhibit halogen substituent dependent localisation in live cells

Abstract

The synthesis and photophysical properties of water responsive 1,10-phenanthrolyl and 2,2′-bipyridyl substituted BODIPY derivatives prepared as lipid probes for cell imaging are reported. These compounds exhibit intense emission in non-aqueous media that is reversibly extinguished in aqueous media. Halogen substitution at the BODIPY indacene core decreases the emission quantum yields and causes red spectral shifts of emission maxima of the order H > Br > I. The emission was quenched on binding of the phenanthrolyl or bipyridyl to cations Fe²⁺, Cu²⁺ and Zn²⁺. The origin of the water switching effect and the impact of halogen substitution was investigated by modelling the electronic structure of the fluorophore using DFT methods. All compounds showed excellent permeability to live cells and were found, under imaging conditions, to generally exhibit low cytotoxicity. The absence of emission in the aqueous environment facilitated the collection of high contrast images from membranous regions and lipid droplets in live cells. The staining pattern in HeLa cells was found to depend on halogen substitution. Across both bpy and phen derivatives the halogenated probes showed the strongest targeting of lipid droplets within cells whilst the parent unsubstituted compounds were more widely dispersed in the cytoplasm. Resonance Raman imaging was used to map the distribution of probes within the cell and confirmed that the compounds showed strong co-localisation with lipid rich regions of the cell.