Synthesis, structure, cytotoxicity, photodynamic reactivities and molecular simulation studies of three [RuNO(Qn)(Pro)Cl] isomeric complexes

Three isomeric nitrosylruthenium complexes [RuCl(Qn)(Pro)(NO)] ( 1 – 3) were prepared, where Qn is 8-hydroxyquinoline and Pro is D-proline. The complexes 1 – 3 were characterized by 1 H-NMR, 13 C-NMR, ESI-MS, and their crystal structure were further determined with X-ray diffraction techniques. In complexes 1 and 3 , the O atom of D-proline coordinated trans to NO, while the O atom of 8-quinolinol coordinated trans to NO in complexes 2 , and the complexes 1 and 3 are the Ru-centered enantiomers. The photo induced NO release of the complexes were explored using time-resolved infrared spectroscopy (FT-IR) and electron paramagnetic resonance spectroscopy (EPR) in solution and the released NO was successfully imaged in living cells using a NO selective fluorescent probe. Furthermore, the cytotoxicity of the isomeric complexes against HeLa, HepG2 and A549 cells were evaluated. Among them, the selectivity for HeLa cells is significant (SI ≥ 5) with IC 50 values in the range of 1.15–1.94 μM. Moreover, the three complexes spontaneously bind to human serum albumin (HSA) through hydrogen bonding and van der Waals forces, the binding constants K b of 1 – 3 are 1.528 × 10 4 , 2.390 × 10 4 and 2.694 × 10 4 M −1 at 298 K, respectively. Molecular docking analyses reveals that 1 – 3 bind within subdomain IB of the protein, which suggest that HSA could be a delivery vehicel for these complexes. This study provides insight into the potential biological and pharmaceutical applications for these isomeric nitrosylruthenium complexes.