Photo and Ultrasound Facilitated the Release of Nitric Oxide From [Ru(NO)(QnCN)(Pro)Cl] Isomers: Synthesis, Cytotoxicity, DNA Binding, and Theoretical Simulation.

Four isomers of [Ru(NO)(QnCN)(Pro)Cl] (L1, D1, L2, and D2) were synthesized, where QnCN is 8-hydroxy-2-quinolinecarbonitrile and Pro is L- or D- proline. Complexes L1 and D1, L2 and D2 are two pairs of Ru-centered enantiomers. In L1 and D1, the proline is coordinated trans to NO, whereas in L2 and D2 the 8-hydroxy-2-quinolinecarbonitrile is coordinated trans to NO. The electronic absorption spectra, infrared (IR), and Raman spectra of the isomers were experimentally measured and theoretically assigned. Ultrasound induces the release of NO from the complexes in solution more rapidly, with a shorter t1/2 than light does. Moreover, the cytotoxicity of the isomeric complexes against HeLa cells was evaluated; the IC50 values range from 1 to 10 µM, with selectivity indices exceeding 2.8. The complexes induced apoptosis in HeLa cells and arrested the cell cycle at the G2/M phase. Molecular docking analyses have revealed that the complexes interact with DNA via minor groove binding. The unique stereochemical configurations of the four complexes affect their selective binding to CT-DNA, with DNA binding affinities at 298 K in the following order: D1 > D2 > L1 > L2. This study offers insights into the potential applications of these isomeric nitrosylruthenium complexes.