Ultrabright Gold Nanoclusters with Intra‐Cluster Hydrogen Bonding Enable Near‐Zero‐Thickness Electrochemiluminescence Imaging of Subcellular Structures

Abstract

Abstract Endowing electrochemiluminescence (ECL) imaging technologies with the capability to resolve fine subcellular structures at high spatial resolution remains a challenging yet critical objective. Achieving this requires ultrasmall ECL emitters coupled with in situ confinement strategies to form near‐zero‐thickness ECL layer. Among available candidates, luminescent gold nanoclusters (AuNCs) have emerged as promising options, but their ECL emission remains too weak for effective microscopic imaging. To overcome this limitation, we report ultrabright AuNCs protected by Cys‐Arg‐Arg‐Arg‐Arg peptides and 6‐aza‐2‐thiothymine (CR 4 /ATT‐AuNCs) as next‐generation ECL emitters. Intra‐cluster hydrogen bonding between neighboring ligands rigidifies their conformation and promotes ordered π–π stacking, significantly enhancing photoluminescence quantum yield (∼60‐fold) and electron transfer efficiency (∼4.8‐fold). This synergistic enhancement activates a previously unreported reduction‐oxidation ECL pathway of AuNCs, resulting in over 250‐fold improvement in ECL intensity. Upon immobilization on electrodes with cells, CR 4 /ATT‐AuNCs generate a robust, near‐zero‐thickness ECL layer visible to the naked eye, directly enabling high‐resolution ECL microscopy that clearly resolves fine subcellular structures down to ∼170 nm. This work presents a powerful strategy for designing ultrasmall high‐performance ECL emitters and demonstrates their potential in advancing the spatial resolution limits of ECL bioimaging.