Rhodamine-Decorated Rhodium(III) Complexes as Theragnostic Agents with Controllable ROS Generation Abilities for Mitochondria-Targeting Type I and Type II Photodynamic Therapy

Though transition metal complexes have been widely developed as potential photosensitizers in photodynamic therapy (PDT), related studies utilizing rhodium(III) complexes are rare due to their less favorable luminescence properties arising from the low-lying d–d excited states and the requirement of high excitation energy. In this work, a series of rhodamine-containing rhodium(III) complexes [Rh(N^C)2bpy-Rho](PF6)2 was designed, synthesized, and characterized to circumvent such problems. It is interesting to note that these complexes exhibited moderate rhodamine fluorescence in solutions under ambient conditions and sensitized a considerable amount of singlet oxygen (1O2) upon photoexcitation. Additionally, some of the complexes were capable of generating superoxide anion radical (O2•–) and hydroxyl radical (HO•) efficiently. Time-resolved transient absorption (TA) spectroscopic results suggested a long-lived dark rhodamine triplet state as a result of the incorporation of the rhodium(III) center, and this lowest-lying state is responsible for the enhanced reactive oxygen species (ROS) photogeneration ability. Instead of the direct population from the singlet (S1) to the triplet state (T1) of rhodamine through intersystem crossing, an energy cascade pathway from rhodamine S1 to a rhodium-based triplet (T1’), and subsequently to the lowest rhodamine T1 was proposed. The ROS photogeneration ability can therefore be readily controlled by a judicious choice of cyclometalating ligands, while an excellent balance between ROS photosensitization and fluorescence can be maintained. Interestingly, live-cell studies revealed that the complexes were localized in the mitochondria, and the photogeneration of ROS triggered a loss of mitochondrial membrane potential, leading to cell death. The complexes exhibited promising photocytotoxicity toward MCF-7 cells, via a combination of type I and type II ROS photosensitization mechanisms. This hybrid rhodamine–rhodium(III) system is anticipated to function as innovative theragnostic agents for both imaging and PDT properties.