Insights into the cytotoxicity of photoactivatable Ru(II) carbonyl complexes towards human liver carcinoma cells

Metal carbonyl complexes have recently been extensively studied as carbon monoxide releasing molecules (CORMs) with the potential to positively affect the biological targets by transferring trace amounts of CO. CORMs have advantageous anti-inflammatory, anti-coagulative, anti-apoptotic, and anti-proliferative properties. In this contribution, three photoactivatable ruthenium(II) carbon monoxide releasing molecules of the general formula [RuCl₂(CO)₂L^R] (L^R = (2-phenyliminomethyl)quinoline derivative), R = OH, OCH₃, and Cl) were synthesized and structurally characterized. Their aerated solutions in DMSO or DMSO-water mixture were stable under the dark conditions. A clear isosbestic point was observed upon the illumination of the complexes at 468 nm due to the release of CO. The position of the isosbestic point in the two media differs, indicating the presence of two distinct forms of the CO depleted species (iCORM). Under the dark conditions, the three complexes exhibited no cytotoxicity against human epithelial-like hepatocellular carcinoma (HepG2) cells. After being exposed to light, the complex, decorated with Cl, demonstrated weak potency. The acquired photocytotoxicity is most likely caused by iCORM, particularly as the cytotoxicity varies according to the diluent used to produce it. Under the dark conditions, the images of fluorescence microscopy showed that the complexes were visible outside the cells. However, the complexes were clearly able to enter the cytoplasmic membrane and maintain their autofluorescence when they were illuminated while the malignant cells were present.