Cellular Membrane‐Targeted Europium(III) Probe for Selective and Time‐Resolved Detection of Peroxynitrite

ABSTRACT Peroxynitrite (ONOO − ) is an extremely short‐lived and highly reactive species whose biological effects depend on its local concentration at the site of formation. Consequently, detecting and quantifying ONOO − requires probes that combine high selectivity with well‐defined subcellular localization. The cell membrane is a particularly important yet underexplored interface, as it is the first barrier encountered by extracellularly generated ONOO − and determines how much of this species penetrates into the cell. Such membrane‐proximal ONOO − formation occurs during inflammatory processes and oxidative stress–based therapies, and is especially relevant in cold atmospheric plasma treatment, where complex RONS mixtures interact with the membrane before intracellular effects arise. Here, we report Eu.Chol , a luminescent europium(III) complex that integrates a phenylboronic acid ONOO − reactive motif with a cholesterol anchor to localize the probe within lipid bilayers. We demonstrate that Eu.Chol incorporates efficiently into liposomes and Jurkat cells, enabling selective, membrane‐localized ONOO − detection with minimal response to H 2 O 2 . These results establish a modular europium(III)‐based scaffold for targeted ONOO − sensing, enabling potential incorporation of organelle‐specific targeting groups to probe RONS dynamics at defined sub‐cellular sites.