Programmable Hierarchical Assembly of Atomically Precise Metal Nanoclusters Using Supra-Amphiphilic Nucleic Acids

Amphiphilic nucleic acids enable programmable supramolecular assembly toward functional nanosystems, yet their typical construction via the covalent conjugation of hydrophobic groups limits architectural versatility. Achieving noncovalent amphiphilic nucleic acid architectures remains a significant challenge. Here, we report a strategy to assemble supra-amphiphilic nucleic acids through noncovalent interactions. The building blocks are partially phosphorothioate-modified single-stranded DNA and hydrophobic, atomically precise gold nanoclusters (Au NCs). The assembly is driven by hydrophobic contacts between nucleobases and the ligand shell of the Au NCs and coordination between the phosphorothioate backbone and the metal core. By precisely modulating the length of the hydrophilic DNA segment, these supra-amphiphiles self-assemble in the presence of Mg²⁺ into well-defined micelles with tunable sizes. The surface-exposed DNA sequences retain their hybridization capability, enabling programmable higher-order assembly through base complementarity. Furthermore, these nanocluster-based micelles can be organized into spatially addressable arrays via DNA origami scaffolds. This strategy establishes a versatile platform for constructing functional nanomaterials with applications in catalysis, bioimaging, and nanodevices.