Molecular engineering of gold nanocluster properties <i>via</i> peptide ligand charge state and topological modulation

The functionalization of gold nanoclusters (AuNCs) with peptides offers a promising strategy for tuning their electronic and optical properties, making them suitable for applications in bioimaging, sensing, and photodynamic therapy. However, the influence of peptide structure, charge state, and length on ligand-to-metal charge transfer (LMCT) and electronic transitions is not yet fully comprehended. In this study, we employ density functional theory (DFT) calculations to systematically investigate the role of linear and cyclic peptides in modulating the optical and electronic properties of AuNCs. In addition, interfragment charge transfer (IFCT) analysis is performed to quantify the charge redistribution between the peptide ligands and the AuNC core. Our findings reveal that zwitterionic peptides exhibit the most significant LMCT, leading to red-shifted absorption peaks and enhanced charge delocalization, while canonical and cyclic peptides display more localized electronic states with reduced charge transfer. Moreover, longer peptide chains, particularly in zwitterionic forms, facilitate increased electronic coupling with the AuNC core, amplifying their optical response. Despite variations in the peptide structure, the AuNC core remains structurally stable, ensuring consistent ligand-core electronic interactions. The IFCT results further confirm that peptide length and structural forms strongly influence charge transfer dynamics, with tetrapeptides exhibiting greater charge redistribution compared to tripeptides. These insights provide a fundamental foundation for the rational design of peptide-functionalized AuNCs with tailored optical and electronic properties. The ability to fine-tune the peptide structure to optimize charge transfer makes these nanoclusters highly promising for biomedical applications, including fluorescence imaging, targeted drug delivery, and molecular sensing. This study advances our understanding of the interactions between peptides and AuNCs and provides the basis for future experimental validation and application-driven modifications.