Design and Synthesis of a Calcium‐Sensitive Photocage

Photolabile protecting groups (or “photocages”) enable precise spatiotemporal control of chemical functionality and facilitate advanced biological experiments. Extant photocages exhibit a simple input–output relationship, however, where application of light elicits a photochemical reaction irrespective of the environment. Herein, we refine and extend the concept of photolabile groups, synthesizing the first Ca(2+)‐sensitive photocage. This system functions as a chemical coincidence detector, releasing small molecules only in the presence of both light and elevated [Ca(2+)]. Caging a fluorophore with this ion‐sensitive moiety yields an “ion integrator” that permanently marks cells undergoing high Ca(2+) flux during an illumination‐defined time period. Our general design concept demonstrates a new class of light‐sensitive material for cellular imaging, sensing, and targeted molecular delivery.