Photo-induced cytotoxicity, photo-controlled nitric oxide release and DNA/human serum albumin binding of three water-soluble nitrosylruthenium complexes

Abstract

Ruthenium (Ru) complexes have been extensively studied for their potential use as DNA structural probes, cellular imaging agents and anticancer drugs due to their favorable photochemistry and photobiological properties. Here, we have synthesized three water-soluble nitrosylruthenium [(CH3)4N][RuCl3(QN)(NO)] complexes using 8-hydroxyquinoline (Hhqn) and its derivatives (2-methyl-8-quinolinoline [H2mqn] and 2-cholo-8-quiolinoline [H2cqn]) as ligands (QN = hqn, 2mqn or 2cqn); their structures were confirmed with X-ray crystal diffraction. The [RuCl3(2cqn)(NO)]− complex shows more activity than the other two complexes, with an IC50 value of 21.5 µM under light and of 100 µM without photoirradiation. The antiproliferative effects induced by the complex arrested the cell cycle at the G2/M phase. Furthermore, photo-controlled real-time NO release from the complexes was confirmed via spin trapping of NO free radicals. The photochemical DNA cleavage of the complexes was also demonstrated, possibly due to photo-induced free radicals. Moreover, the binding constants of the complexes with calf thymus DNA and human serum albumin were calculated by fluorescence spectroscopy to understand the effects of the substituent groups on the biological activity. The [RuCl3(2cqn)(NO)]− complex had the highest binding constant, consistent with its high cytotoxicity. Thus, we developed an effective and simple method to control cytotoxic activities using photoactive [RuCl3(QN)(NO)]− complexes, which has potential therapeutic applications in medicine and biological science.

Publication Title

Polyhedron

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