Mechanistic Insights into Label-Free SERS Discrimination of Structurally Similar Small-Molecule Biomarkers: A DFT Study of 4-HBA and 4-HPAA on Au Clusters

In this study, density functional theory (DFT) calculations were employed to investigate the interactions between structurally similar small molecules, 4-hydroxybenzoic acid (4-HBA) and 4-hydroxyphenylacetic acid (4-HPAA), and Au-enhanced substrates in the context of surface-enhanced Raman scattering (SERS). The calculated molecular electrostatic potential (ESP) results indicate that both molecules exhibit pronounced electronegativity at the carboxyl and hydroxyl groups, suggesting that these re