Title : Integrated Raman, SERS and computational approaches for the study of bioactive molecules in pharmaceutical chemistry
Abstract:
Raman and surface-enhanced Raman scattering spectroscopy have become valuable tools in pharmaceutical chemistry because they combine molecular selectivity, limited sample preparation and the possibility of analysing compounds in different physical states. This contribution presents an integrated spectroscopic and computational approach for the structural investigation of pharmaceutically relevant molecules, with particular attention to active pharmaceutical ingredients, antimicrobial compounds and bioactive derivatives interacting with metallic substrates.
Conventional Raman and micro-Raman spectroscopy were employed to obtain characteristic molecular fingerprints, identify functional groups and evaluate structural changes associated with solid-state organization, polymorphism and intermolecular interactions. These techniques offer a non-destructive strategy for examining pharmaceutical materials while preserving the sample for complementary analyses. Surface-enhanced Raman scattering measurements performed on silver- and copper-based substrates produced a marked amplification of weak vibrational signals and enabled the investigation of adsorption processes occurring at the drug–metal interface. Changes in band position, relative intensity and spectral profile were interpreted in relation to molecular orientation, surface affinity and possible charge-transfer contributions.
Density functional theory calculations supported the assignment of the experimental vibrational bands and helped identify the most probable molecular conformations and adsorption geometries. Comparison between calculated and experimental spectra was particularly useful for distinguishing closely related structural forms and for determining which functional groups were directly involved in interactions with metallic surfaces. In selected systems, molecular docking and molecular dynamics simulations were also used to explore the binding of bioactive compounds to relevant biological targets and to assess the stability of the predicted complexes over time.
The combined methodology provided complementary information at different levels, from the identification of pharmaceutical compounds to the interpretation of their molecular behaviour in complex environments. Raman spectroscopy proved effective for rapid and non-destructive characterization, whereas SERS increased analytical sensitivity and revealed subtle molecular changes that were not readily detectable through conventional measurements. The computational component strengthened spectral interpretation, reduced ambiguity in band assignment and offered a molecular-level explanation for experimentally observed changes.
Particular attention was devoted to the relationship between chemical structure, spectroscopic response and interaction mechanism. This relationship is essential in pharmaceutical research, where small conformational or solid-state differences may affect stability, solubility, bioavailability and biological activity. The ability to monitor such differences without extensive sample treatment makes vibrational spectroscopy especially attractive for studying drug candidates, formulations and functionalized nanomaterials.
Overall, the results highlight the potential of Raman and SERS spectroscopy, integrated with computational chemistry, as a versatile platform for pharmaceutical analysis. The proposed strategy may contribute to active-ingredient characterization, investigation of drug–nanomaterial interactions, development of label-free sensing methods and rational study of bioactive molecules. Its flexibility supports applications ranging from quality control and formulation studies to early-stage drug discovery and the design of advanced analytical systems for pharmaceutical research.
