Shape-Sensitive Fragmentation in Mass Spectrometry Informs Structural Differences of Thiolated Gold Nanoclusters

Thiolated gold nanoclusters (Au NCs), comprising a gold core protected by outer-layer staple motifs, have attracted widespread interest due to their promising applications in catalysis, biosensing, and biomedicine. While mass spectrometry (MS) is widely used to determine the chemical composition of Au NCs via intact mass measurement, its potential for in-depth structural analysis via gas-phase fragmentation in tandem MS remains largely underexplored. Herein, we used collision-induced dissociation (CID) and surface-induced dissociation (SID) to investigate the dissociation pathways of four Au NCs featuring distinct symmetries and structural motifs: dimeric staples (S-Au-S-Au-S) and trimeric staples (S-Au-S-Au-S-Au-S). While ligand loss of-R groups and-SR (thiolated ligands) were observed as the main pathway, unique-2-Au/-4-Au loss specific to trimeric staples was observed only in SID. In addition, the collision energy required to breakdown each Au NCs varied in different ways in CID and SID, implying a shape-sensitive fragmentation mechanism. Supported by ion mobility data and literature reports, the faster heating in SID may access more fragmentation pathways than CID, thereby allowing more structural informative fragments to be generated. These findings not only provided critical insights into the gas-phase chemistry of Au NCs but also highlighted the potential of MS-based strategies for the structural elucidation of Au NCs that are intractable to conventional methods.