Fluorescent Ru(II) and Re(I) terpyridine complexes: anticancer activity, cellular uptake, and mechanisms of cell death.

A cytotoxicity screening of two metal carbonyl compounds of 4'-(2,3,4-trimethoxyphenyl)-2,2':6',2″-terpyridine (1, terpy234) with the formulas cis-[RuCl(CO)2(terpy234-κ3N1N2N3)]Cl (2) and fac-[ReBr(CO)3(terpy234-κ2N1N2)] (3) was conducted on three cancerous and one normal cell line. Analytical and spectroscopic data confirmed that 1 exhibited different coordination modes toward Re(I) and Ru(II) ions, coordinating via bi- and tridentate modes of chelation. The two complexes could be localized within cells owing to their intrinsic fluorescence properties. Cell death, the onset of necrosis and apoptosis, and the integrity of the cell membrane were all used to assess the impact of the complexes on the tested cells. The cytotoxicity of 3 was higher than that of 2, and it was even more effective against liver and breast cancer models than the standard cisplatin. Early on, 3 and cisplatin showed a combination of necrosis and apoptosis that started at distinct times compared to 2. With more LDH release in 3 and cisplatin, the integrity of the cell membrane was generally more damaged than with 2. While cisplatin and 3 raised the mitochondrial membrane potential (MMP), compound 2 selectively inhibited it in a cell-dependent manner. Cisplatin and both complexes inhibited the synthesis of ATP. Complexes 2 and 3 exhibited cell-dependent oxidative stress, as measured by ROS and the NADP+/NADPH ratio, but cisplatin was universally effective in causing oxidative stress.