C9-Aryl-substituted berberine derivatives with tunable AIE properties for cell imaging application

Berberine (BBR), a widely used isoquinoline alkaloid derived from natural sources, exhibits aggregation-induced emission (AIE) characteristics and has biological applications such as in selective lipid droplet imaging and photodynamic therapy. However, natural BBR suffers from low fluorescence quantum yield (Φ_F) and monotonous emission wavelength. In this paper, a series of C9-position-aryl-substituted berberine derivatives with a D-A structure were designed and synthesized. The electronic effect of the substitution groups can tune the intramolecular charge transfer (ICT) effect of the berberine derivatives, resulting in bluish green to NIR (508-682 nm) luminescence with AIE characteristics and enhanced Φ_F up to 36% in the solid state. Interestingly, berberine derivatives containing an amino or a pyridyl group can exhibit fluorescence response to TFA. Cell imaging of the berberine derivatives was conducted using Caco-2 cancer cells, demonstrating their multi-color and efficient wash-free imaging capabilities. This work presents a new strategy for developing novel berberine derivatives with tunable AIE properties for application in biological imaging.