Application of terahertz time domain spectroscopy on real-time monitoring the generation of 8-hydroquinolinium salicylate

8-hydroquinolinium salicylate is kind of salt with enhanced dissolution rate and bioavailability by forming intermolecular hydrogen bonds between 8-hydroxyquinolinium cations and salicylate anions. Based on the correspondence between intermolecular hydrogen bonds and the molecular vibrational modes, the THz fingerprints of 8-hydroquinolinium salicylate and its parent molecules were systematically investigated by terahertz time-domain spectroscopy combined with theoretical calculations. It is demonstrated that there are substantial differences between THz fingerprints of 8-hydroquinolinium salicylate and the ones of its parent molecules in the range of 0.2-2.0 THz, such as the number, amplitude and frequency positions of absorption peaks. By combining Hirshfeld surface analysis with the 2D fingerprint diagrams, the pattern of intermolecular hydrogen bonds (including O5-⸱⸱⸱H3+-N1, O8-⸱⸱⸱H4+-N2 as well as π⸳⸳⸳π interactions) was obtained within the molecular system of 8-hydroxyquinolinium salicylate. Furthermore, the full geometry optimizations were performed and all THz absorption peaks were assigned to their corresponding vibrational modes by employing dispersion-corrected density functional theory. It is confirmed that there are significant differences between 8-hydroxyquinolinium salicylate and its parent molecules for the weak intermolecular hydrogen bonds and the corresponding vibrational modes. Moreover, the THz absorption spectra of products of 8-Hydroxyquinoline and salicylic acid were also obtained in reaction process at different times. It is exhibited that there are important changes with time for the amplitude and frequency position of THz absorption peaks. All of above results provide valuable insights for monitoring the chemical and biological processes of pharmaceutical compounds in real time by THz-TDS.