Interaction between Molnupiravir and noble metal substrates in SERS detection: A DFT method and Raman characteristic study

Molnupiravir, a nucleoside analogue (EIDD-2801), is an RNA polymerase inhibitor that effectively treats infections caused by novel coronaviruses and can be administered orally. Therefore, it is necessary to monitor the distribution of Molnupiravir in vivo after oral administration. Surface-enhanced Raman spectroscopy (SERS) is a suitable detection method, so it is necessary to understand the interaction between Molnupiravir and noble metal nanoparticles in the SERS effect. Therefore, we used density functional theory combined with surface-enhanced Raman spectroscopy to investigate the interaction between Molnupiravir and noble metal/composite nanoparticles in the SERS effect. To study the interaction sites of Molnupiravir and the substrate in the SERS effect, the molecular electrostatic potential (MEP) of Molnupiravir was calculated. Considering the significant role of binding energy in studying molecular docking, the binding energy between Molnupiravir and Metal₆ (Au₆, Ag₆, Au₃Ag₃) atomic clusters was calculated. The calculated results of the frontier orbitals and relevant molecular parameters of Molnupiravir and Molnupiravir-Metal₆ complexes reveal the changes in the molecular properties of Molnupiravir in the SERS effect. Finally, the theoretical Raman spectra differences between Molnupiravir and complexes were compared and analyzed, and the adsorption structure of Molnupiravir on the substrate surface was determined based on the surface selection rules of SERS. The research results will provide insights into the interaction between Molnupiravir and the substrate in the SERS effect, and also offer theoretical support for the application of SERS methods in biomedical detection.