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 μM) toward various cancer cells in the dark, the corresponding T1-T3 complexes exhibit much stronger cytotoxic effects (IC₅₀ = 3.7-39.4 μM). C1 can be readily photoconverted into T1 upon visible-light irradiation (white light), as shown by UV/vis and ¹H 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.