Surface Charge Mosaic of a Water-Soluble Au25( p -MBA)18 Nanocluster Induced by Environment’s pH

Water-soluble monolayer-protected gold nanoclusters (AuNCs) are widely regarded as promising nanomaterials for biological and biomedical applications, yet the impact of the environment’s pH on their surface charge distribution is poorly understood, hampering efforts to rationally design the cluster size and ligand chemistry for optimizing reactivity and solvation. To investigate the pH effect, we used the constant-pH molecular dynamics simulation method for statistical sampling of ligand charge distributions in a water-soluble gold nanocluster protected by para-mercaptobenzoic acid ligands, Au25(p-MBA)18, in a wide pH range of 1 to 11. The results showed three macroscopic pKa values for the ligand layer: 2.25 ± 0.01, 5.68 ± 0.02, and 6.23 ± 0.04, and indicated anticooperative deprotonation behavior with Hill coefficients ranging from 0.74 to 0.34. The ligand layer pattern and interligand aromatic interactions explained the observed order of ligand deprotonation. These results uncover ligand-specific deprotonation behavior of Au25(p-MBA)18, enabling precise tuning of its functional performance across diverse applications in biological environments.