Solvent-Assisted Iridium(III) Complexes as Ligand-Exchange Luminescent Probes for L-Histidine Sensing and Cell-Death Imaging

Coordination lability is a useful chemical handle for constructing reaction-based photoluminescence (PL) probes from cyclometalated Ir(III) complexes. In this study, the solvent-ligated Ir(III) complexes Ir-DMSO, Ir-DMF, Ir-Py, and Ir-EDA were generated from a dichlorobridged precursor Ir2(ppy)4(μ-Cl2) by direct solvent–ligand exchange. Their comparative behavior shows that the analytical response is controlled by the balance between precursor stability and ligand displacement. Ir-DMF and Ir-DMSO displayed selective PL turn-on responses to L-histidine (L-His) among the 20 common amino acids, whereas Ir-Py and Ir-EDA remained poorly responsive, as stronger pyridine binding or ethylenediamine chelation reduced the availability of the Ir(III) center for exchange. Ir-DMF performed the best, with a linear L-His response of over 0.1–10 μM (R2 = 0.9923) and detection limit of 39 nM. ESI–MS revealed the presence of mono- and bis-His Ir adducts, supporting an imidazole-driven ligand-exchange mechanism. Lifetime measurements further showed an increase from 0.175 to 0.488 μs after Ir-His formation, consistent with a more emissive and structurally restricted product. In HeLa cells, Ir-DMF showed low cytotoxicity at imaging concentrations and preferentially stained PI-positive membrane-compromised cells. These results establish solvent–ligand lability as a practical design variable for Ir(III)-based L-His sensing and reaction-guided cell-death imaging.