A Reactive and\nSpecific Sensor for Activity-Based <sup>19</sup>F‑MRI Sensing\nof Zn<sup>2+</sup>

The rapid fluctuations of metal ion levels in biological\nsystems\nare faster than the time needed to map fluorinated sensors designed\nfor the <sup>19</sup>F-MRI of cations. An attractive modular solution\nmight come from the activity-based sensing approach. Here, we propose\na highly reactive but still ultimately specific synthetic fluorinated\nsensor for <sup>19</sup>F-MRI mapping of labile Zn<sup>2+</sup>. The\nsensor comprises a dipicolylamine scaffold for Zn<sup>2+</sup> recognition\nconjugated to a fluorophenyl acetate entity. Upon binding to Zn<sup>2+</sup>, the synthetic sensor is readily hydrolyzed, and the frequency\nof its <sup>19</sup>F-functional group in <sup>19</sup>F-NMR is shifted\nby 12 ppm, allowing the display of the Zn<sup>2+</sup> distribution\nas an artificial MRI-colored map highlighting its specificity compared\nto other metal ions. The irreversible Zn<sup>2+</sup>-induced hydrolysis\nresults in a “turn-on” <sup>19</sup>F-MRI, potentially\ndetecting the cation even upon a transient elevation of its levels.\nWe envision that additional metal-ion sensors can be developed based\non the principles demonstrated in this work, expanding the molecular\ntoolbox currently used for <sup>19</sup>F-MRI.