Transformable cis-trans isomerism of ruthenium(ii) complexes with photoactivated anticancer activity

Photoactivated chemotherapy (PACT) provides a new alternative cancer treatment strategy compared to conventional therapy. In this study, a series of diisocyano ruthenium(II) complexes Ru(PBO)(2)(RNC)(2) containing the 2-benzoxazol-2-ylphenolate (PBO) auxiliary ligand and their potential application as PACT agents are reported. The complexes exhibit two geometric isomers, i.e., trans, trans, trans (T1-T3) and cis, trans, cis (C1-C3) forms. Although C1-C3 show minimal cytotoxicity (IC50 = 60.1 to >100 mu M) toward various cancer cells in the dark, the corresponding T1-T3 complexes exhibit much stronger cytotoxic effects (IC50 = 3.7-39.4 mu M). C1 can be readily photoconverted into T1 upon visible-light irradiation (white light), as shown by UV/vis and H-1 NMR spectroscopy. The increased toxicity of the T-form is partially attributed to its reaction with glutathione, in contrast to the C-form analogue. The anticancer activities of T1 were studied in vitro and in vivo. This is the first study that demonstrates the photoisomerization of the isocyano ruthenium(II) complex Ru(PBO)(2)(CNR)(2) as an attractive approach for PACT.