Rational Design of Lysosome-Targeted Iridium(III) Complex for HClO Imaging and Monitoring Drug-Induced Bidirectional HClO Dynamics

Abstract A series of Ir(III) complexes targeting lysosomes and bearing an imino ortho phenylene HClO recognition unit was developed for selective HClO imaging. In these probes, electrophilic addition triggered by HClO at the recognition unit modulates emission from the Ir(III) coordination core, representing the first use of this reaction mode in an organometallic HClO probe. The optimized probe exhibited a rapid and highly selective luminescence response to HClO over competing reactive oxygen species, radicals, and biologically relevant ions, together with strong signal enhancement suitable for sensitive biological detection. Spectroscopic studies and theoretical calculations validated the proposed reaction pathway and clarified the molecular origin of the emission response to HClO. The probe localized precisely in lysosomes and enabled visualization of exogenous and endogenous HClO in living cells, multicellular spheroids, and living animals. Importantly, quantitative in vivo imaging enabled evaluation of drug efficacy through treatment-dependent HClO changes. Antiallergic treatment decreased the luminescence signal, consistent with reduced HClO levels, whereas antitumor treatment enhanced the signal, indicating HClO accumulation. This discrimination of opposite pharmacological responses supports the probe as a valuable tool for HClO imaging, therapeutic response monitoring, and mechanistic studies of HClO-related drug action.