BODIPY (boron dipyrromethene) derivatives and Ru(II) complexes are two types of functional compounds that have found wide applications in the fields of biology and medicine. We herein synthesized two new Ru(II) arene complexes based on an iodized BODIPY-containing pyridine (py-I-BODIPY) ligand, [(p-cym)Ru(bpy)(py-I-BODIPY)]²⁺ (2) and [(p-cym)Ru(2-pydaT)(py-I-BODIPY)]²⁺ (3), where p-cym = para-cymene, bpy = 2,2′-bipyridine, and 2-pydaT = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine. The photophysical, photochemical and photobiological properties of 2 and 3 were compared with that of [(p-cym)Ru(bpy)(py-BODIPY)]²⁺ (1). While 1 undergoes efficient monodentate ligand dissociation upon visible light irradiation and therefore may photobind DNA as a potential photoactivated chemotherapy (PACT) agent, 2 and 3 can generate ¹O₂ effectively and thus may serve as photosensitizers in photodynamic therapy (PDT). In electrophoresis experiments, 2 and 3 are even able to retard the mobility of plasmid DNA in the dark at high concentrations. More importantly, the cytotoxicities of 2 and 3 against human ovarian adenocarcinoma SKOV3 cells are enhanced about ten times under irradiation, leading to cytotoxicities more than one order of magnitude higher than that of cisplatin, demonstrating an efficient hybridization of the iodized BODIPY chromophore and the Ru(II) arene complex.

Three chloromethyl-modified Ru(II) complexes were designed and synthesized as mitochondria targeting photosensitizers, which can generate carbon radicals in the presence of NADH under visible light irradiation, cause DNA cleavage and covalent binding in Ar-saturated solutions, and lead to apoptosis of human ovarian carcinoma SKOV-3 cells under hypoxic conditions (3% O₂), demonstrating a new mode of type I mechanism to overcome the limitation of hypoxia in photodynamic therapy (PDT).

Photoactivated chemotherapy (PACT) is a novel cancer treatment method that has drawn increasing attention due to its high selectivity and low side effects by spatio-temporal control of irradiation. Compared with photodynamic therapy (PDT), oxygen-independent PACT is more suitable for treating hypoxic tumors. By finely tuning ligand structures and coordination configurations, many Ru(II) complexes can undergo photoinduced ligand dissociation, and the resulting Ru(II) aqua species and/or free ligands may have anticancer activity, showing their potential as PACT agents. In this mini-review, we summarized the progress in Ru(II)-based PACT agents, as well as challenges that researchers in this field still face.

Transition metal complexes with dual functions of DNA photobinding via coordination and DNA photocleavage via¹O₂ may present potent antitumor activities with high selectivity and a wide anticancer spectrum. We herein report such a complex, [(η⁶-p-cymene)Ru(dpb)(py)]²⁺ (dpb = 2,3-bis(2-pyridyl)benzoquinoxaline, py = pyridine, 1). The highly delocalized nature of dpb provides 1 with long wavelength-absorbing properties and a long-lived excited state, facilitating ¹O₂ generation. Additionally, the bulky nature of dpb leads to a distorted coordination geometry, and allow the ³MC (metal-centered) state to be more accessible. From this, dissociation of py and dpb may occur, followed by the coordination of the resultant Ru fragment to nucleic bases if DNA is present. The dissociation of dpb can turn on fluorescence of its own, enabling real-time imaging of the photoactivation process. The fascinating properties of 1 and the underlying mechanisms that occur may provide guidelines for developing more efficient metallodrugs with dual potential for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT).