Influence of Ligand Engineering on Intrinsic Chirality of Gold Nanoclusters

Chirality in atomically precise gold nanoclusters arises from the complex interplay between the metallic core, the Au–S interface, and the surrounding ligand shell. Understanding how these elements cooperate or compete during chemical modification is essential for tailoring chiroptical properties. Here, we investigate how ligand engineering influences intrinsic chirality in two prototypical chiral nanoclusters, Au 38 (SR) 24 and Au 144 (SR) 60 , which differ fundamentally in the origin of their chirality. Bidirectional ligand exchange (LEx) reactions were performed between the chiral 2‐methyl‐1‐butanethiol (2‐MeBuSH) and achiral 2‐phenylethanethiol (2‐PET) ligands, and the reaction progress was monitored by matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS), Fourier‐transform infrared (FTIR), and circular dichroism (CD) spectroscopy. For Au 38 , exchange of achiral for chiral ligands induced a structural transformation toward the enantiomeric form, matching the ligand handedness, evidencing ligand‐driven chiral amplification. The reverse exchange, however, preserved the original enantiomer, indicating that once formed, Au 38 maintains its intrinsic chirality. In contrast, Au 144 displayed only limited ligand substitution and negligible changes in chiroptical response, consistent with its higher inversion barrier and structural rigidity. These findings establish how intrinsic and ligand‐derived chirality cooperate, or compete, during postsynthetic modification, offering molecular‐level insight into the design of stable, enantiomerically enriched nanomaterials.