Work

Phosphorescent Iridium(III) Phenanthrolinedione Complexes as Lifetime‐Responsive Bioorthogonal Probes for Wash‐Free Time‐Resolved Bioimaging of Cellular Labeling

Year: 2025

Type: article

Abstract: Fluorogenic bioorthogonal probes are crucial tools in biomedical research, which enable non-invasive, wash-free imaging of specific biomolecules in living systems. Lifetime-responsive bioorthogonal probes represent another promising and attractive alternative, offering the potential for real-time, wash-free visualization of bioorthogonal labeling processes via photoluminescence lifetime imaging microscopy (PLIM). However, their widespread application is limited by the lack of suitable lifetime-responsive probes. Herein, a series of phosphorescent iridium(III) phenanthrolinedione complexes were reported. Intriguingly, upon bioorthogonal reaction with an α-angelica lactone derivative, the complexes exhibited remarkable emission responses in three distinct manners, which were found to correlate with the different emissive excited states of the complexes. Crucially, two of the complexes maintained similar emission intensity but exhibited significant emission lifetime elongation during labeling reactions, which facilitated simultaneous and discriminative visualization of the reacted and unreacted probes in cellular imaging without the need for washing steps. One of the complexes was used for organelle targeting and specific protein labeling through bioorthogonal reactions in living cells. The intracellular probe transportation and labeling dynamics were visualized and analyzed using PLIM. This work highlights the unique potential of lifetime-responsive iridium(III) complexes as powerful chemical tools for live-cell imaging and unveiling the spatiotemporal dynamics of biomolecules during bioorthogonal reactions.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.202504230