Tuning the surface chemistry of NHC-protected Au₁₃ nanoclusters <i>via</i> a robust amide coupling procedure

There is significant potential use for gold nanoclusters in biomedicine owing to their favorable biological and optical properties. To access this potential, there is a need for methods to alter the ligand scaffold of gold nanoclusters to tune their biological properties. Surface modifications to the ligands must occur with molecular precision to generate monodisperse products for the accurate determination of structure activity relationships and eventual translation to clinical practice. Herein, we describe methods for molecularly precise surface modifications to Au₁₃ nanoclusters <i>via</i> amide couplings to -COOH functionalities and their stability to conditions necessary for the removal of protecting groups used in amide coupling chemistry. These clusters were found to be highly stable to basic conditions for the removal of base-labile -Fmoc and -OMe groups but less stable to acidic conditions for the removal of acid-labile -Boc and -O ^<i>t</i> Bu groups. The ligand shell and Au₁₃ core of such clusters were found to be preserved following modifications to the ligand shell allowing the solubility and biological properties of the cluster to be altered independently of their optical properties. The nature of the protecting ligand was found be instrumental for cluster stability to enable the use of the harsh conditions necessary to yield monodisperse products.