C6N8 carbon-nitride monolayer as a sensitive SERS-active sensor and carrier for methimazole: DFT, solvent and docking insights

This study uses density functional theory (B3LYP/6-311++G*) to investigate how a C6N8 carbon-nitride monolayer interacts with the antithyroid drug methimazole (MHZ), and to assess the monolayer’s potential as both a sensor (including SERS-like Raman enhancement activity) and a drug carrier. Three adsorption orientations (A1-A3) were optimized and analyzed in vacuum and aqueous media. All complexes are strongly stabilized: interaction energies in vacuum are -218.12, -216.75 and -211.90 kcal mol-1 (A1-A3) and become even more favorable in water (-238.73, -233.13, -232.30 kcal mol-1). The pristine C6N8 band gap (3.89 eV) narrows upon complexation (vacuum: 1.79-3.10 eV; water: 2.94-3.26 eV), consistent with charge transfer from MHZ (HOMO) to C6N8 (LUMO). TD-DFT and vibrational analyses show new and shifted modes indicative of increased polarizability and SERS-like Raman enhancement. Noncovalent interaction analyses (RDG and ELF) indicate that A2 and A3 are dominated by van-der-Waals contacts, while A1 displays both strong electrostatic (hydrogen-bond like) attraction and VDW contributions; ELF maps support electron delocalization consistent with long-range noncovalent binding. Docking against protein 7XW5 yields substantially improved scores for the complexes (≈ -136 to -152 versus free MHZ (-68), suggesting C6N8 could also function as a drug-delivery scaffold. Overall, the C6N8 monolayer shows promising selectivity, strong adsorption, SERS-like Raman enhancement responsiveness and dual utility as a sensor and carrier for MHZ.