Rational design fluorescent dyes based on morpholine derivatives for specific imaging of lysosomes and lipid droplets in living cells

Lysosomes and lipid droplets (LDs), as two crucial sub-organelles within cells, play a pivotal role in maintaining the normal cellular functions. However, rational design and synthesis of fluorophores that selectively target specific organelles still pose a challenge. Herein, we developed a series of eight fluorescent dyes (LCA1-LCA4 and LCN1-LCN4) containing morpholine moiety, which effectively targeting lysosome and LDs within cells through rational regulation of substituents in the molecular structure. Among these compounds, compounds LCA1/LCN1 containing triphenylamine group and LCA3/LCN4 containing coumarin group exhibit specific targeting towards the LDs, whereas compound LCN2 containing carbazole group demonstrates targeted localization to lysosome. Moreover, these five compounds displayed the advantages of high cellular viability, excellent resistance to interference, pH insensitivity and the ability to enter cells without washing. Compounds LCN2 and LCA1 are capable of real-time monitoring the dynamic behavior of lysosome and LDs respectively, as well as the mitophagy (LCN2) or the number and diameter variations of LDs (LCA1). The results provide a potential candidate for specific lysosomes and LDs imaging.