Surface Regulation Towards Stimuli‐Responsive Luminescence of Ultrasmall Thiolated Gold Nanoparticles for Ratiometric Imaging

Abstract The surface chemistry of the ultrasmall thiolated gold nanoparticles (AuNPs, < 3.0 nm) plays key roles in both governing the intrinsic emission and establishing interfaces surrounded by various amine‐containing biomolecules in the biomedical applications such as imaging, targeting, and diagnostics. However, a fundamental understanding of the surface ligand's role in the stimuli‐responsive emissions of AuNPs toward the amine molecules is currently lacking. Here, through investigation of the thiolate surface and exotic amine structures, it is discovered that the nucleophilic amines tend to closely bind the electrophilic gold surface, generating a high‐energy stimuli‐responsive emission from the low‐energy intrinsically emitting AuNPs. Both the intrinsic and stimuli‐responsive emissions show a unique amine concentration‐dependent ratiometric pattern for quantitative assessments of important biogenic amines in the biological samples. This discovery opens a new pathway to the design of stimuli‐responsive AuNPs, and would promote more experimental and theoretical research on the application‐driven surface engineering for advanced biological applications.