A Novel Substituted Benzo[]quinoxaline-Based Cyclometalated Ru(II) Complex as a Biocompatible Membrane-Targeted PDT Colon Cancer Stem Cell Agent.

Herein, we describe and investigate biological activity of three octahedral ruthenium(II) complexes of the type [Ru(CN)(phen)], -, containing a π-expansive cyclometalating substituted benzo[]quinoxaline ligand (CN ligand) (phen = 1,10-phenanthroline). Compounds - in cervical, melanoma, and colon human cancer cells exhibit high phototoxicity after irradiation with light (particularly blue), with the phototoxicity index reaching 100 for the complex in most sensitive HCT116 cells. accumulates in the cellular membranes. If irradiated, it induces lipid peroxidation, likely connected with photoinduced ROS generation. Oxidative damage to the fatty acids leads to the attenuation of the membranes, the activation of caspase 3, and the triggering of the apoptotic pathway, thus implementing membrane-localized photodynamic therapy. is the first photoactive ruthenium-based complex capable of killing the hardly treatable colon cancer stem cells, a highly resilient subpopulation within a heterogeneous tumor mass, responsible for tumor recurrence and the metastatic progression of cancer.