5-Hydroxy- <scp>L</scp> -tryptophan Adsorbed at the Silver Nanoparticle Surface: Conformational Geometries Revealed by SERS and Multiscale Modeling

5-Hydroxy-L-tryptophan (5-HTP) is a biologically relevant metabolite and a promising optical probe. However, its vibrational properties have remained poorly characterized. In this work, we present a comprehensive normal Raman and surface-enhanced Raman scattering (SERS) study of 5-HTP by combining experimental results with molecular dynamics (MD) simulations and density functional theory (DFT) calculations. The DFT calculation accurately reproduced the normal Raman spectrum of 5-HTP, which confirmed the zwitterionic nature of the molecule in the solid state. We also report here, for the first time, the SERS spectrum of 5-HTP using silver nanoparticles. The SERS spectrum revealed significant differences in the relative band intensities compared to the normal Raman spectrum, which is related to the adsorption and orientation of the molecule at the metal surface. MD simulations considering neutral and charged silver surfaces showed that 5-HTP does not adopt a unique configuration but interacts primarily through the carboxylate group and often with the indole ring tilted or parallel to the surface. DFT calculations of 5-HTP adsorbed on silver clusters of ten atoms further support these findings and allow us to describe the role of both chemical and electromagnetic effects in the intensity enhancement. This work reported the Raman fingerprint of 5-HTP and its SERS enhancement mechanisms, offering new possibilities for future application of this molecule as a Raman probe in biochemical sensing and protein structure studies.