A Smart Supramolecular Strategy Fine-Tunes the Molecular Aggregation Behavior to Overcome the Aggregation-Caused Quenching (ACQ) Barrier in Precise Bioimaging of Active Analytes

Fluorescent molecular probes are commonly used to detect active substances. However, in variable living microenvironmental systems, most of conventional aromatic fluorescent probes often suffer from aggregation-caused quenching (ACQ) due to π-π stacking, which severely limit their selectivity and sensitivity. To tackle this challenge, a predictable supramolecular strategy, which offers significant spatial effects to prevent fluorophore’s intermolecular π-π stacking at the molecular level, was proposed to design fluorescent probes. Herein, supramolecular probe RAA@Q[8] was successfully integrated by loading an adamantane-modified Rhodamine derivative (RAA) into cucurbit[8]uril (Q[8]) via the host-guest recognition principle. Intriguingly, the original highly clustered RAA-agminated spheroids become discrete supramolecular organic framework octahedrons (RAA@Q[8]), suggesting that the molecular aggregation behavior is well-modulated. This encouraging result is important for precise detection of plant signaling molecules such as salicylic acid (SA) in various environments. Experimental investigations found that RAA@Q[8] was 2.2-fold more sensitive than RAA for detecting SA, with high selectivity and anti-interference, and a low detection limit of 3.0×10 -8 M. Importantly, in complicated living microenvironments, RAA@Q[8] achieved a precise recognition and imaging of SA on pea sprouts and HEK-293 cells. This study offers a guidance for future development of host-guest supramolecular fluorescent probes that are opposite to the intractable ACQ obstacle.