An Engineered Supramolecular Pathway for Enhanced Electrochemiluminescence

ABSTRACT Electrochemiluminescence (ECL) underpins ultrasensitive clinical assays, yet current platforms are largely dominated by antibody‒antigen immunoassay formats, which are intrinsically difficult to translate to small‐molecule detection. The limited size of small molecules, together with the lack of multiple accessible epitopes, restricts the applicability of conventional sandwich architectures and calls for alternative recognition strategies capable of directly coupling molecular binding to ECL signal generation. Herein, we introduce a supramolecular ECL approach in which a recognition unit (cucurbit[7]uril) is covalently integrated with an ECL‐active luminophore (tris(2,2′‐bipyridyl)ruthenium(II), [Ru(bpy) 3 ] 2+ ) to create a compact, self‐contained, and recognition‐responsive emitter. This architecture provokes an intramolecular ECL generation pathway by preorganizing the protonated coreactant tri‐ n ‐propylamine (TPrA) inside the host, leading to a 162% increase in ECL intensity compared to the benchmark [Ru(bpy) 3 ] 2+ /TPrA system, and modulating [Ru(bpy) 3 ] 2+ excited‐state properties through dynamic intramolecular host–guest interactions. Competitive binding of small molecules, including clinically relevant metabolites and hormones, perturbs this intramolecular equilibrium and reprograms both ECL mechanism and enhancement, enabling highly sensitive yet antibody‐free detection down to the nanomolar range in buffered media. Hence, our results establish a general supramolecular design principle for the first self‐contained, recognition‐responsive ECL emitter, opening avenues toward modular and host‒guest engineered platforms for chemically programmed ECL transduction.