Organic and Metallacages for Chemical Sensing: Progress in Water‐Compatible Systems

ABSTRACT Supramolecular cages are powerful tools for molecular recognition and sensing, using well‐defined nanoscale cavities to encapsulate ions, small molecules, and biologically relevant guests with notable selectivity. Over the past three decades, these systems have progressed from simple conceptual assemblies to sophisticated covalent and organometallic architectures that operate in water as chemosensors, delivery vehicles, and separation p. Their analyte detection relies on diverse signal transduction mechanisms, including luminescence, circular dichroism, and Förster resonance energy transfer, enabling the sensing of anions, cations, chiral molecules, drugs, explosives, and environmental pollutants. Relative to classical receptors, cages offer notable advantages such as three‐dimensional preorganization, modular functionalization, and the incorporation of multiple recognition sites within a single discrete framework. However, their broader implementation in real‐world settings is still hampered, primarily by challenges in achieving sufficient stability in water and complex biological fluids. This review outlines design principles for water‐stable cages, discusses analyte‐specific and medium‐related challenges, and surveys recent examples of water‐compatible systems, including their integration into polymeric materials. Finally, we provide a perspective on next‐generation cage‐based chemosensors, emphasizing advanced readout strategies and potential applications in diagnostics, environmental monitoring, and biomedicine.