Leveraging Host–Guest Assemblies toward Simultaneous Intensification of Phosphorescence and Nanozyme Activity for Triple-Modal Hypochlorous Acid Detection

The integration of multimodal sensing capabilities into a single platform remains a significant challenge for advanced biomedical diagnostics. Herein, a novel supramolecular strategy leveraging host-guest assembly is developed to simultaneously enhance room-temperature phosphorescence (RTP) and nanozyme activity for triple-modal hypochlorous acid (HClO) detection. Tricomponent hydrogen-bonded organic frameworks (HOFs), formed via coassembly of a melamine-cyanurate (H-CA) host with electron-deficient aromatic acid guests, exhibit ultralong RTP (lifetime up to 868 ms) and superior peroxidase-like (POD) activity. Theoretical and experimental studies reveal that host-guest interactions rigidify the microenvironment, promote intersystem crossing (ISC), and narrow the energy gap, thereby boosting both the phosphorescence and electron-transfer efficiency. Capitalizing on this synergy, a multifunctional probe (Eu@MC-TAT) enables self-validating triple-modal detection of HClO through ratiometric fluorescence, phosphorescence lifetime signaling, and colorimetric readouts. The resulting probe achieves rapid, ultrasensitive detection of HClO via three complementary channels, excellent selectivity against interferents, and recyclability. Demonstrations in serum samples and a portable hydrogel device (SA-Eu@MC-TAT) underscore its clinical potential. This work pioneers a supramolecular approach to unify phosphorescence enhancement and nanozyme optimization, opening avenues for multimodal biosensing.