Luminescent Iridium(III) Polypyridine Complexes Modified with a Molecular Glue as Photofunctional Cellular Reagents

Over the last decade, transition metal complexes (TMCs) has gained considerable attention due to their excellent photophysical and photochemical properties. The introduction of cleavable dendritic molecular glue to transition metal complexes (TMCs) can create a new class of molecular glue-modified TMCs, which can be utilized as imaging, labeling, and therapeutic regents. In this project, two novel cyclometalated iridium(III) complexes containing stimuli-response linkers tethered to multiple guanidinium moieties as molecular glues for the delivery and controlled release of active biomolecules in cancer were designed. The binding of the molecular glue complexes to the biomolecules inhibits their activity, which can be reversed after cleavage of the linker in response to esterase in cancer. Additionally, this cleavage process simultaneously releases the iridium(III) complexes, leading to changes in emission intensity and lifetimes that can be used to monitor the delivery and release of the biomolecules. This work provides luminescent molecular glues that can inhibit and deliver biomolecules, release and activate them, and monitor the process in tumor tissues.