Red-light Emitting Orthogonally Trireactive Gold Nanoclusters for the Synthesis of Multifunctionalized Nanomaterials.

For the development of highly multifunctionalized nanomaterials, the introduction of functional molecules on gold nanoclusters containing thiols preinstalled with connecting groupsconstitutes a promising approach. However, the uniform introduction of multiple connecting groups while avoiding side reactions is a challenging task. Herein, the synthesis of gold nanoclusters (ca. 1 nm) coated with thiol peptides bearing azido, amino, and aminooxy groups is reported. These nanoclusters emit red-light before and after the functionalization, enabling application to cell imaging. A detailed structure analysis using transmission electron microscope and X-ray absorption spectroscopy reveals the formation of Au(SR) nanoclusters as promising motifs for red-light emission. The sequential modification of the trireactive nanoclusters with RGD (Arg-Gly-Asp) peptides, metal chelators, and anticancer drugs via [3+2] cycloaddition, oximation, and amidation reactions at each functional group furnish red-light-emissive nanomaterials exhibiting remarkable toxicity against A549 human lung cancer cells. Integration of the multiligation chemistry and gold nanocluster engineering pave the way toward the development of advanced multifunctional nanomaterials for biological applications.