Structural Impact of Acetylation on the Adsorption of Gold Nanoclusters on Human Serum Albumin: Spectroscopic, Electrochemical, and Molecular Simulation Insights

Gold nanoclusters (AuNCs) have attracted attention in biomedical applications such as bioimaging, drug delivery, and disease diagnostics due to their low toxicity and tunable optical properties. The adsorption behavior of AuNCs on serum proteins is crucial for their in vivo stability and functionality. Here, we investigated the interaction between cysteine and acetylated cysteine stabilized AuNCs and human serum albumin (HSA), focusing on how ligand acetylation modulates the structural and optical properties of the resulting AuNCs-HSA complexes. Spectroscopic, electrochemical, and molecular simulation analyses revealed that acetylation did not alter the quenching mechanism or the primary binding forces between AuNCs and HSA. However, the presence of acetyl groups induced a shift in the binding mode. Molecular docking suggested that acetyl oxygen atoms formed stabilizing intermolecular hydrogen bonds with HSA at Site I, enhancing binding strength. Furthermore, conformational studies showed that acetylation altered the microenvironment of key residues, potentially affecting the luminescent characteristics of the AuNCs-HSA complex. These findings provide valuable insight into how surface ligand engineering influences the structural and photophysical behavior of AuNCs-HSA systems, offering new perspectives for their application in luminescence-based biomedical technologies.