Experimental and theoretical SERS spectra: the case of Ampicillin

Surface enhanced Raman scattering (SERS) spectroscopy is a powerful tool for the study of structure, symmetry and orientation of molecules adsorbed on metal surfaces. It is a highly sensitive technique useful to detect species present at a trace level concentrations and to gather information concerning metal-adsorbate interactions. The study of drug molecules adsorbed on metallic substrate is becoming critical in future applications like drug delivery, bio-active surfaces, bio and chemical nano-sensors, etc. Moreover, the study of interaction of drug molecules with metals in solution can provide useful information on the biological activity of such molecules. Ampicillin or 6-[D(-)α-aminophenylacetamido] penicillanic acid is a well-known penicillin class antibiotic with betalactamic structure, which is getting new attention for drug resistance problems. In the past we have studied the existing polymorphic and solvate forms by different analytical techniques and by comparing experimental and theoretical data (C. Baraldi, A. Tinti, S. Ottani, M.C. Gamberini, J. Pharm. Biomed. Analysis 100 (2014) 329-340). In this work, ampicillin SERS spectrum at 10-4 M concentration was studied and discussed. The adsorption geometry of the ampicillin molecule on colloidal silver surface was deduced from the SERS selection rules. In addition, Density Functional Theory (DFT) computations on a couple of Ag atoms or AgCl interacting with different ampicillin groups were performed, to obtain theoretical spectra for the interpretation of the SERS experiments. Interactions with Ag colloidal surfaces have been approximated by placing an Ag2 cluster in positions close to electron donor groups of the ampicillin molecule (i.e. the carboxylic group (zwitterion), the sulfur atom (zwitterion), the aromatic ring (zwitterion), the -NH2 group (anion) and the tautomeric -COOH/-NH2 group). For the ampicillin the aug-cc-pVDZ (aug-cc-pV(D+d)Z for Sulfur atom) basis set was used, whereas the Ag atoms were modeled by the lanl2dz basis set. Calculations were performed with an implicit solvent model (CPCM). Computations led to stable optimized geometries with the exception of -NH3+/Ag2 (viz. the ampicillin in zwitterionic form) since such a group has a marked electrophilic character. Interpretation of the theoretical frequency spectra was performed by the Potential Energy Distribution (PED) analysis of the fundamental vibrations modes. According to the theoretical results, SERS experiments demonstrated that ampicillin was adsorbed in tilted orientation on silver colloid; the interaction mainly takes place by means of the benzenic ring and the aminic group.