Indolizino[3,2-c]quinolines as environment-sensitive fluorescent light-up probes for targeted live cell imaging

Abstract

Live cell imaging using small organic fluorophores has emerged as a powerful non-invasive approach to visualizing a variety of cellular processes. We recently reported the design and synthesis of indolizino[3,2-c]quinolines (IQs), a fused heterocyclic system, as a potential candidate for novel fluorescent probes. Here, we explored the environment-sensitive features of the IQs in a cellular context using fluorescent microscopy to achieve no-wash live cell imaging with precise spatial control. Elucidating the cellular targets of IQs based on their chemical structures has enabled us to develop organelle-specific fluorophores that target DNA (3C2), RNA (3B1 and 3H1), and lysosomes (IQ-MP1 and IQ-MP2) in live cells. These compounds exhibit good cell membrane permeability, high photostability, and low cytotoxicity with good compatibility in aqueous systems, properties that are rarely encountered together. 3H1, with a large Stokes shift, exhibits counterstain compatibility when combined with DNA probes (Hoechst 33258) in live cells. The properties of the IQs described here suggest that these compounds may serve as important tools for investigating dynamic processes in live cells.