Compartmentalized Amplification and Spectral Engineering of Luminol Chemiluminescence via Host–Guest Cavity Binding and Amphiphilic Self‐Assembly
Jie Gao, Hongchao Wang, Maocheng Yang, Yujie Wang, Meng‐meng Chen, Yumei Wu, Zhe Zheng, Chunju Li, Zeli YuanABSTRACT
Luminol chemiluminescence (CL) is widely used in bioanalysis and forensics, yet stringent alkalinity, flash‐type kinetics, and blue emission strongly hinder in vivo applications. Here, we report QC4A‐8C, a single compartmentalized supramolecular platform that simultaneously addresses these limitations. QC4A‐8C is an amphiphilic quaternary ammonium calix[4]arene with orthogonally functionalized upper and lower rims. The cationic cavity selectively encapsulates luminol, induces a p K a shift, and converts luminol into a glow‐type emitter at near‐physiological pH. In parallel, the hydrophobic lower rim self‐assembles into nanoaggregates that compartmentalize fluorescent acceptors (DTBT, MCCH, DCI) in nanometer proximity, enabling sequential chemiluminescence resonance energy transfer (CRET) with high efficiency and red‐shifted emission (650–700 nm). As a result, tissue penetration and emission lifetime are substantially extended, and in a lipopolysaccharide‐induced peritonitis model, QC4A‐8C delivers pronounced signal enhancement over free luminol. This work validates macrocyclic host–guest chemistry as a programmable route to integrate CL amplification with optical spectral engineering for diagnostic imaging.