Photoinduced NO release of [Fe2(μ-SL)2(NO)4] complexes and their protein adducts: insights from structure, cytotoxicity, and photodynamic studies†

The dinitrosyl iron complex (DNIC) is a ubiquitous functional brick often used as a vehicle for the NO radical and chelatable iron pool, with a key role in chemical and biomedical applications. In this work, four DNICs modified with different thiolate bridging ligands (–SL) were synthesized. These complexes were characterized by ¹H-NMR, electrospray ionization mass spectrometry, and X-ray crystal diffraction. Photoinduced NO release from the complexes in solution was further explored by time-resolved infrared and electron paramagnetic resonance (EPR) spectroscopy. The cluster complexes showed relatively lower cytotoxicity against the normal human liver cell line HL-7702 and higher cytotoxicity against human cervical cancer cells, with a selectivity index of 2.4–4.8. The cluster complexes with different L groups had different rates of NO release and protein binding constants. Moreover, NO released upon photoirradiation entered living cells, which were successfully imaged using an NO-selective fluorescent probe. The ferritin complex adducts further enhanced the cytotoxicity and cellular fluorescence intensity of NO, and the crystal structure revealed the coordination of the Fe(SL)₂ unit with Cys102 of ferritin. This study provides insight into the photodynamic mechanism of nitrosyl iron–sulfur clusters to understand their physiological activity.