TY - JOUR

T1 - Ambroxol: Insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study

AU - Alkhimova, Larisa

AU - Sharov, Artem

AU - Burkhanova, Tatyana

AU - Babashkina, Maria

AU - Safin, Damir

N1 - This work was supported by state assignment of the Ministry of Science and Higher Education of the Russian Federation (Project Reg. No. 720000Ф.99.1.БЗ85АА13000). We thank Ural Interregional World-class Scientific and Educational Center "Advanced Production Technologies and Materials" for the support of this work.

PY - 2023/3/16

Y1 - 2023/3/16

N2 - 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···N and O–H···O hydrogen bonds and C–Br···π interactions. The Hirshfeld molecular surface is characterized by intermolecular contacts H···X (X = H, C, N, O, Br) and C/O/Br···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···N and O–H···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).

AB - 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···N and O–H···O hydrogen bonds and C–Br···π interactions. The Hirshfeld molecular surface is characterized by intermolecular contacts H···X (X = H, C, N, O, Br) and C/O/Br···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···N and O–H···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).

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U2 - 10.1080/10406638.2022.2049323

DO - 10.1080/10406638.2022.2049323

M3 - Article

VL - 43

SP - 2599

EP - 2617

JO - Polycyclic Aromatic Compounds

JF - Polycyclic Aromatic Compounds

SN - 1040-6638

IS - 3

ER -