Fusion of photodynamic therapy and photoactivated chemotherapy: a novel Ru(ii) arene complex with dual activities of photobinding and photocleavage toward DNA

Abstract

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).