Low Energy Vibrations and Crystalline Structure of Ambroxol Hydrochloride by THz Spectroscopy and DFT Calculations

Dr. Tereza Uhlíková, MSc. Ivana Šlechtová, Dr. Jan Koucký, Dr. Patrik Kania, Dr. Jan Rohlíček, Prof. Dr. Štěpán Urban

Abstract

The widely used drug ambroxol hydrochloride (A-HCl), was subjected to analysis by terahertz time domain (THz-TDS) spectroscopy and quantum chemistry calculations. The performed X-ray measurement confirmed the C2/c crystallographic group for A-HCl. On the contrary, the presented theoretical calculations, achieved by solid-state density functional theory (ss-DFT), determined the structure in the global minima on potential energy surface which belong to the Cc crystallographic group. In the frame of this symmetric group, the ss-DFT calculations resulted in 40 vibrational normal modes up to wavenumber 110 cm⁻¹. The three different functionals (B3LYP, PBE, and PW1PW) were applied and all of them provided similar results. In the same range of wavenumbers (10–110 cm⁻¹) the THz spectrum was measured at two different temperatures (room and cryogenic). Thanks to the very good correspondence of the experiment and calculations in both position and intensities of the peaks, we were able to analyze each peak from percentage contributions of inter- and intra-molecular movements point of view and trivial nomenclature for such complex normal modes was suggested as well.

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