## 3 Results and Discussion
### SERS Applications
#### 3.2.4 Discrimination of Propranolol Enantiomers by SERS with CD Decorated NPs  
The SERS spectrum of propranolol both on Ag and AuNPs was already presented in our previous papers [15; 47; 48]. As we already presented the SERS spectrum of propranolol is dominated by the vibrations of the naphthyl group, which enters in its composition. In Figure 12 we compare the SERS spectra of naphthalene and propranolol demonstrating their similarity. The main vibration found in naphthalene at 1378 cm\({}^{-1}\), 1562 cm\({}^{-1}\), 756 cm\({}^{-1}\), and 510 cm\({}^{-1}\) can be found in _mutatis mutandis_, also in the spectrum of propranolol. Moreover, these vibrations of the naphthyl group are the most intense ones in the propranolol SERS spectrum. In previous work, we also demonstrated both experimentally and theoretically that there is a much stronger interaction between the R enantiomer of propranolol compared with its S counterpart with the cavity of \(\beta\)-CD [15]. While both enantiomers penetrate the \(\beta\)-CD cavity, R-propranolol penetrates deeper into the cavity and can form hydrogen bonds with the host. This stronger interaction is reflected in the SERS spectra by the appearance of new vibrations in the spectra of the R-propranolol \(\beta\)-CD system. Moreover, the spectra were more intense in the case of citrate-reduced AuNPs compared with hydroxyl amine-reduced AgNPs, in correlation with the observations made above. These results were obtained by preincubating the propranolol enantiomers with \(\beta\)-CD for about 1 h at room temperature, before adding them to the plasmonic colloids. We tested our newly synthesized colloids if they were able to discriminate between the two propranolol enantiomers based on their SERS spectra. Without using aggregating agents or using salts with low affinity to the metallic surface (MgSO\({}_{4}\), (NH\({}_{4}\))\({}_{2}\)SO\({}_{4}\)), the SERS spectra present a very weak intensity and their profile is similar to the ones obtained with classical colloids, being dominated by the naphthyl group vibrations. However, when using KI or KBr as aggregating agents, we noticed a time evolution of the SERS spectra leading to the shape presented in Figure 13. The strongest peak at \(\sim\)1380 cm\({}^{-1}\) decreases its intensity and other new peaks, marked in Figure 13, increase their intensities. Moreover, there is a clear difference between the two enantiomers, with R-propranolol presenting the highest SERS intensity peaks. This result correlates with the stronger interaction and  
Figure 12: SERS spectra of naphthalene and propranolol obtained on citrate-reduced gold colloids. The wavenumber corresponding to the most intense vibrational bands belongs to the naphthyl group and is marked in the figure. formation of hydrogen bonds between R propranolol and \(\beta\)-CD, reported previously [15] based on density functional theory (DFT) calculations. Most probably these results can be explained by a change in the orientation of the analytes relative to the metallic surface and a much stronger interaction. We noted that the prepared and aggregated samples preserved their SERS properties for several months. However, it is difficult to assess the exact orientation of the molecule based on SERS spectra. The assignments of the vibrational bands of propranolol (Table S2) [47] based on DFT cannot offer a clear-cut answer as probably the strong interactions occurring after aggregation lead to important shifts. It is also possible that due to the rigidity of CD molecules, there is a limitation in the vibrational mode of the naphthyl group and an increase in the intensity of other vibrations. Indeed, from Table S2, one can see that the intense vibrations recorded at low wavenumbers 422 cm\({}^{-1}\) and 477 cm\({}^{-1}\) are assigned to NH bending and CH rocking and at 818 cm\({}^{-1}\) to CCC symmetric stretching. The most intense band recorded at 1225 cm\({}^{-1}\) might be related to \(\tau\)(CH) + \(\delta\)(CH) measured at 1245 cm\({}^{-1}\) in the absence of CD.