KCS

Copper ions play essential roles in various biological systems and its homeostasis is tightly controlled in the mammalian cells. However, imbalances in copper homeostasis are responsible for defects in copper export systems and central nervous system in Wilson’s disease as a genetic disorder by mutated ATP7B gene. Copper toxicity may contribute to the generation of reactive oxygen species (ROS), which can lead to cellular damage, oxidative stress and DNA damage. Its cytotoxic effects may involve malfunction of various organelles although the excess of copper ions is mainly accumulated in lysosome in the hepatocytes. However, its effect on subcellular organelle functions or copper uptake pathways is poorly understood. Therefore, we present the synthesis and development of organelle-selective fluorescent Cu²⁺ sensors, 1 and 2, bearing naphthalimide and dipicolylamine (DPA) units. Confocal microscopic images indicated that probes 1 and 2 are mainly localized in ER and lysosome, respectively. Upon addition of the excess copper ions to the living cells, probe 1 showed strongly quenched fluorescence intensity. Furthermore, inhibition of copper export system by sodium metavanadate (NaVO₃), aggravates fluorescence quenching of probe 1, suggesting that the ER is the primary site for copper reservoir in the overloading condition. Therefore, organelle selective probe 1 could be a valuable tool to understand the detailed role of copper ions. In addition this approach could be applied to diagnose pathogenesis related to the copper ion level changes.