Steric Engineering of Perylene Derivative Side Chains To Boost Electrochemiluminescence for High-Performance Bioanalysis

Traditional organic planar aromatic emitters often encounter low electrochemiluminescence (ECL) efficiency due to the aggregation-induced quenching (ACQ) induced by π-π stacking, limiting their applicability in bioanalysis. In this work, we proposed a steric engineering strategy to mitigate ACQ in perylene diimide-bridged β-cyclodextrin aggregates (Pe-CD aggregates), significantly boosting their ECL efficiency for trace microRNA (miRNA) detection. By incorporation of a large steric volume of cyclic β-cyclodextrin (β-CD) at both side chains of perylene diimide, the Pe-CD molecules were generated and further assembled into robust supramolecular nanoblocks. This strategy modulates the intermolecular distances around the perylene cores, effectively minimizing nonradiative relaxation. Molecular simulation and ECL results demonstrated that the intermolecular distance of Pe-CD aggregates increased from 3.32 Å to 5.21 Å, accompanied by a 5.8-fold enhancement in ECL efficiency compared to Pe aggregates (formed by the dense π-π stacking of planar molecules). As a proof of concept, an ECL bioassay platform was developed using the Pe-CD aggregates as emitters and the target-enrichment accelerated-3D DNAzyme walkers as signal amplifiers for detecting miRNA-21, achieving a limit of detection as low as 9.7 aM. This study offers valuable insights for designing new organic planar aromatic ECL emitters and expands the potential applications of ECL technology.