Near-quantitative yield of atomically precise gold nanoclusters by decoupling precursor-to-intermediate reduction from nucleation.

Water-soluble metal nanoclusters comprising a few to hundreds of metal atoms hold great promise for bioimaging, catalysis, and beyond. However, their practical use remains hindered by low synthetic yields and insufficient product purity. This limitation stems primarily from the concurrent generation and nucleation of highly reactive intermediates during conventional chemical reduction, a process that unavoidably leads to the formation of structurally ill-defined byproducts. Here we show that an intermediate-decoupled strategy separates intermediate generation from nucleation via a sequential two-stage reduction. Specifically, Au(III) precursors are first converted into Au(I)-thiolate intermediates using a mild reductant, followed by rapid nucleation triggered by a strong reductant. This stepwise reduction suppresses competing pathways, drives near-complete precursor-to-intermediate conversion, and affords atomically precise nanoclusters in yields approaching 100% and purities exceeding 90% without further purification. The method is demonstrated at a reaction volume of 2000 mL and is applicable to nanoclusters of different sizes and thiolate ligands. Our work provides mechanistic insight into the controlled growth of nanoclusters and establishes a synthesis strategy for improving product yield and purity and for scaling up metal nanocluster synthesis.