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 time-resolved electron paramagnetic resonance (EPR) spectra. 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 fluorescent 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.