DFT, spectroscopic and MD insights into teneligliptin (TLG) adsorption on Cu3 and Cu(111): Implications for SERS sensing and drug-metal interfaces

Surface-enhanced Raman scattering (SERS) platforms and metal-drug nano-interfaces require a clear, site-resolved understanding of how pharmaceutical molecules bind to small metal clusters and extended metal surfaces. Here, we investigate the interaction of the anti-diabetic drug Teneligliptin (TLG) with a Cu3 cluster using density functional theory (DFT), complemented by vibrational (Raman/IR) analysis and molecular dynamics (MD) simulations on Cu(111). Geometry optimizations, frequency calculations, and electronic descriptors were obtained at the B3LYP/SDD level (Gaussian16), and adsorption was explored through six binding configurations (TLG1-TLG6) guided by electrostatic/reactive regions of the drug. Adsorption is exothermic for all complexes, with calculated adsorption energies spanning −16.51 to −33.75 kcal mol−1, indicating strong site dependence; the most stable binding occurs for configurations involving heteroatom-rich motifs (notably TLG4 and TLG3). Cu3 adsorption substantially perturbs the electronic structure of Teneligliptin, reducing the energy gap relative to the isolated drug (≈ 4.997 eV) and enhancing global reactivity descriptors, consistent with facilitated charge transfer and improved electronic response upon complex formation. Mulliken charge analysis confirms net electron redistribution to the metal moiety across all adsorbed systems. Sensor-relevant kinetics were assessed via recovery time estimates at 400 K, revealing that TLG1 and TLG2 provide the most practical trade-off between adsorption strength and reversibility, whereas the strongest-binding systems exhibit excessively long recovery times. Simulated Raman spectra show adsorption-induced band shifts (including carbonyl/NH downshifts) and the emergence of new low-frequency modes characteristic of metal-molecule coupling, supporting SERS-activity changes upon binding. Finally, MD simulations on Cu(111) indicate stable surface association dominated by dispersive interactions with localized adsorption contacts and partial charge redistribution, consistent with mixed physisorption/weak chemisorption behavior. Overall, the combined DFT-spectroscopic-MD framework clarifies how binding site selection controls stability, electronic tenability, and sensing practically for Teneligliptin at copper-based interfaces.