Multiple organelle-targeted 1,8-naphthyridine derivatives for detecting the polarity of organelles

Abstract

Four 1,8-naphthyridine derivatives (1a–1d) with different organelle targeting abilities were obtained using the Knoevenagel condensation reaction of 1,8-naphthyridine with 4-(N,N-diethylamino)benzaldehyde (2a), 4-(N,N-diphenylamino)benzaldehyde (2b), 4-(piperazin-1-yl)benzaldehyde (2c) and 4-(ethyl(4-formylphenyl)amino)-N-(2-((4-methylphenyl)sulfonamido)ethyl)butanamide (2d), respectively. The maximal absorption bands of dyes 1a–1d were observed at 375–447 nm, while their maximum emission peaks were situated at 495–605 nm. The optical properties showed that the fluorescence emission of dyes 1a–1d is shifted toward greater wavelengths as the system polarity (Δf) increased. Meanwhile, with increasing polarity of the mixed 1,4-dioxane/H₂O system, the fluorescence intensity of dyes 1a–1d gradually decreased. Furthermore, the fluorescence intensity of 1a–1d enhanced by 12–239 fold as the polarity of 1,4-dioxane/H₂O mixtures declined. 1a–1d had a large Stokes shift (up to 229 nm) in polar solvents in comparison to nonpolar solvents. The colocalization imaging experiments demonstrated that dyes 1a–1d (3–10 μM) were located in mitochondria, lipid droplets, lysosomes and the endoplasmic reticulum in living HeLa cells, respectively; and they could monitor the polarity fluctuation of the corresponding organelles. Consequently, this work proposes a molecular design idea with different organelle targeting capabilities based on the same new fluorophore, and this molecular design idea may provide more alternatives for polarity-sensitive fluorescent probes with organelle targeting.