Ligand‐Dependent Cytotoxicity and Fluorescence Imaging of Coumarin‐based Zinc (II) Complexes

ABSTRACT

In this work, four coumarin‐based Zn(II) complexes, Zn‐CT6 , Zn‐CT7 , Zn‐CT8 , and Zn‐NCT , were synthesized. The complexes exhibit ligand‐dependent solid‐state emission ranging from cyan to red, whereas appreciable solution fluorescence is mainly observed for Zn‐NCT . TD–DFT calculations support the assignment of the dominant absorption bands and provide qualitative insight into the locally excited and charge‐transfer characters of the electronic transitions. Biological evaluation revealed that Zn‐CT7 and Zn‐CT8 display moderate cytotoxicity toward A549, MCF‐7 and HepG2 cancer cells (IC ₅₀ ∼ 10 µM). DNA‐binding studies indicate that the complexes interact with calf thymus DNA through a predominantly non‐intercalative binding mode, most plausibly groove‐associated binding. Additional cellular assays suggest that Zn‐CT8 induces intracellular ROS generation, mitochondrial membrane potential (MMP) depletion, and apoptosis‐associated morphological changes. Exploratory docking and 300 ns molecular dynamics simulations against the GLP‐1 receptor complex provide qualitative structure‐based hypotheses for future target‐validation studies. To improve aqueous dispersibility, a Tween‐80 micellar formulation of Zn‐CT8 was prepared and physicochemically characterized. Finally, Zn‐NCT showed efficient cellular uptake and preferential endoplasmic‐reticulum/mitochondrial localization in HeLa cells, supporting its utility as an intracellular fluorescent probe. Overall, these results establish ligand‐dependent relationships among structure, photophysics, DNA interaction, cytotoxicity, and cellular imaging behavior in coumarin‐based Zn(II) complexes.