Ambroxol: Insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study

We report detailed studies of Form II of ambroxol, which crystal packing was examined in detail by a Hirshfeld surface analysis. Molecules in the crystal structure are primarily linked through the N-H center dot center dot center dot N and O-H center dot center dot center dot O hydrogen bonds and C-Br center dot center dot center dot pi interactions. The Hirshfeld molecular surface is characterized by intermolecular contacts H center dot center dot center dot X (X = H, C, N, O, Br) and C/O/Br center dot center dot center dot Br. The overall topology of the energy distributions in the crystal structure of Form II of ambroxol was also established. The structure is mainly characterized by the dispersion interactions. The title compound was further studied by IR and UV-vis spectroscopy. Intermolecular N-H center dot center dot center dot N and O-H center dot center dot center dot O hydrogen bonds dictate the clearly revealed discrepancies between the experimental and calculated IR spectra in the region of 3000-4000 cm(-1). The DFT/B3LYP/6-311++G(d,p) calculations were performed to verify the structure of Form II of ambroxol as well as its electronic and optical properties. Molecular docking was applied to examine the influence of ambroxol on a series of the SARS-CoV-2 proteins. The molecule of ambroxol interacts much more efficiently with a series of studied proteins in comparison to Favipiravir, showing the best binding affinity with RdRp-RNA and nsp14 (N7-MTase).