Visible light-induced cytotoxicity of a dinuclear iron(III) complex of curcumin with low-micromolar IC50 value in cancer cells

• This is the first report of a photocytotoxic Fe(III) complex of curcumin.
• The complex is remarkably photocytotoxic in light but non toxic in dark.
• Hydrolytic instability of curcumin is arrested on binding to Fe(III).

Photoactive metal complexes have emerged as potential candidates in the photodynamic therapy (PDT) of cancer. We present here the synthesis, characterization and visible light-triggered anticancer activity of two novel mixed-ligand oxo-bridged iron(III) complexes, viz., [{Fe(L)(acac)}2(μ-O)](ClO4)2 (1) and [{Fe(L)(cur)}2(μ-O)](ClO4)2 (2) where L is bis-(2-pyridylmethyl)-benzylamine, acac is acetylacetonate and cur is the monoanion of curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione). The crystal structure of complex 1 (as PF6− salt, 1a) shows distorted octahedral geometry of each iron(III) centre formed by the FeN3O3 core. The 1:2 electrolytic complexes are stable in solution and retain their oxo-bridged identity in aqueous medium. Complex 2 has a strong absorption band in the visible region and shows promising photocytotoxicity in HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 3.1 ± 0.4 μM and 4.9 ± 0.5 μM while remains non-toxic in the dark (IC50 > 50 μM). The control complex 1 is inactive both in the light and dark. Complex 2 accumulates in cytoplasm of HeLa and MCF-7 cells as evidenced from fluorescence microscopy and triggers apoptotic cell death via light-assisted generation of reactive oxygen species (ROS). Taken together, complex 2 with its promising photocytotoxicity but negligible dark toxicity in cancer cells has significant photochemotherapeutic potential for applications in PDT.

A mixed-ligand iron(III) complex of curcumin and dipicolylamine base shows remarkable visible-light induced apoptotic cytotoxicity in HeLa and MCF-7 cancer cells but shows no toxicity in dark.Figure optionsDownload as PowerPoint slide