Functionalized Au15 nanoclusters as luminescent probes for protein carbonylation detection

Atomically precise, ligand-protected gold nanoclusters (AuNCs) attract considerable attention as contrast agents in the biosensing field. However, the control of their optical properties and functionalization of surface ligands remain challenging. Here we report a strategy to tailor AuNCs for the precise detection of protein carbonylation—a causal biomarker of ageing. We produce Au 15 SG 13 (SG for glutathione) with atomic precision and functionalize it with a thiolated aminooxy moiety to impart protein carbonyl-binding properties. Mass spectrometry and molecular modelling reveal the key structural features of Au 15 SG 12 -Aminooxy and its reactivity towards carbonyls. Finally, we demonstrate that Au 15 SG 12 -Aminooxy detects protein carbonylation in gel-based 1D electrophoresis by one- and two-photon excited fluorescence. Importantly, to our knowledge, this is the first application of an AuNC that detects a post-translational modification as a nonlinear optical probe. The significance of post-translational modifications in life sciences may open avenues for the use of Au 15 SG 13 and other nanoclusters as contrast agents with tailored surface functionalization and optical properties. Atomically precise gold nanoclusters hold promise as non-linear optical probes for biological imaging. Here functionalized luminescent gold nanoclusters bind free carbonyls via oxime bond formation, allowing detection of carbonylated proteins via gel electrophoresis and fluorescence imaging.