Mitochondria-targeting cyclometallated rhodium(iii) complexes appended with two rhodamine units as Type I photosensitisers for bioimaging and photocytotoxicity applications by inducing pyroptosis

Abstract

Cyclometallated rhodium(III) complexes have been underexplored as photosensitisers due to their low-lying d–d excited states, which result in weak visible-light absorption and non-emissive properties, coupled with a modest heavy atom effect that limits reactive oxygen species (ROS) generation. In this work, a series of cyclometallated rhodium(III) polypyridine complexes appended with two rhodamine units [Rh(N^C)₂(bpy-diRho)](PF₆)₃ was rationally designed as Type I photosensitisers. These complexes exhibited intense absorption in the visible region and moderate rhodamine fluorescence in solution upon photoexcitation. Time-resolved transient absorption spectroscopy revealed a long-lived rhodamine-based triplet excited state as the lowest-lying excited state in this hybrid system, which is attributed to the presence of the rhodium(III) centre and is responsible for ROS photosensitisation. Notably, these rhodium(III) complexes efficiently generated superoxide anion (O₂˙⁻) and hydroxyl (HO˙) radicals via the Type I pathway upon photoirradiation, likely via intramolecular electron transfer between the two adjacent excited rhodamine units within the complex to form radical cation and anion. Cellular colocalisation studies demonstrated that these complexes predominantly accumulated in mitochondria, where the photosensitised ROS triggered significant mitochondrial dysfunction, resulting in their outstanding photocytotoxicity under both normoxic and CoCl₂-induced hypoxic conditions. Further mechanistic investigations revealed that the photoinduced mitochondrial ROS generation triggered cancer cell death via gasdermin D-mediated pyroptosis. This rhodium(III)–dirhodamine system further explores the utilisation of rhodium(III) complexes as phototheranostic agents and underscores their potential in this role.