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Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study

In this work we report structural and computational studies of favipiravir, which is now used as a drug for COVID-19 treatment. The molecule is completely flat and stabilized by an intramolecular O–H···O hydrogen bond, yielding a six-membered pseudo-aromatic ring. The aromaticity index of this pseud...

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Autores principales: Babashkina, Maria G., Frontera, Antonio, Kertman, Alexander V., Saygideger, Yasemin, Murugavel, Swaminathan, Safin, Damir A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189275/
http://dx.doi.org/10.1007/s13738-021-02285-x
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author Babashkina, Maria G.
Frontera, Antonio
Kertman, Alexander V.
Saygideger, Yasemin
Murugavel, Swaminathan
Safin, Damir A.
author_facet Babashkina, Maria G.
Frontera, Antonio
Kertman, Alexander V.
Saygideger, Yasemin
Murugavel, Swaminathan
Safin, Damir A.
author_sort Babashkina, Maria G.
collection PubMed
description In this work we report structural and computational studies of favipiravir, which is now used as a drug for COVID-19 treatment. The molecule is completely flat and stabilized by an intramolecular O–H···O hydrogen bond, yielding a six-membered pseudo-aromatic ring. The aromaticity index of this pseudo-aromatic ring was found to be 0.748, while the same indix for the pyrazine ring in favipiravir was found to be 0.954. The crystal packing of favipiravir is mainly constructed through intermolecular N–H···O, N–H···N and C–H···O hydrogen bonds, yielding a 3D supramolecular framework with a zst topology defined by the point symbol of (6(5)·8). The crystal structure of favipiravir is further stabilized by weak C–F···F–C intermolecular type II dihalogen interactions, yielding a 1D supramolecular polymeric chain. More than 80% of the total Hirshfeld surface area for favipiravir is occupied by H···H/C/N/O/F and C···N/O contacts. Energy frameworks have been calculated to additionally analyze the overall crystal packing. It was established that the structure of favipiravir is mainly characterized by the dispersion energy framework followed by the less significant electrostatic energy framework contribution. Finally, by using density functional theory (DFT) calculations and the quantum theory of atoms in molecules, we have assigned the interaction energy of each hydrogen bond, which can be helpful to develop scoring functions to be used in force fields/docking calculations.
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spelling pubmed-81892752021-06-10 Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study Babashkina, Maria G. Frontera, Antonio Kertman, Alexander V. Saygideger, Yasemin Murugavel, Swaminathan Safin, Damir A. J IRAN CHEM SOC Original Paper In this work we report structural and computational studies of favipiravir, which is now used as a drug for COVID-19 treatment. The molecule is completely flat and stabilized by an intramolecular O–H···O hydrogen bond, yielding a six-membered pseudo-aromatic ring. The aromaticity index of this pseudo-aromatic ring was found to be 0.748, while the same indix for the pyrazine ring in favipiravir was found to be 0.954. The crystal packing of favipiravir is mainly constructed through intermolecular N–H···O, N–H···N and C–H···O hydrogen bonds, yielding a 3D supramolecular framework with a zst topology defined by the point symbol of (6(5)·8). The crystal structure of favipiravir is further stabilized by weak C–F···F–C intermolecular type II dihalogen interactions, yielding a 1D supramolecular polymeric chain. More than 80% of the total Hirshfeld surface area for favipiravir is occupied by H···H/C/N/O/F and C···N/O contacts. Energy frameworks have been calculated to additionally analyze the overall crystal packing. It was established that the structure of favipiravir is mainly characterized by the dispersion energy framework followed by the less significant electrostatic energy framework contribution. Finally, by using density functional theory (DFT) calculations and the quantum theory of atoms in molecules, we have assigned the interaction energy of each hydrogen bond, which can be helpful to develop scoring functions to be used in force fields/docking calculations. Springer Berlin Heidelberg 2021-06-09 2022 /pmc/articles/PMC8189275/ http://dx.doi.org/10.1007/s13738-021-02285-x Text en © Iranian Chemical Society 2021 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Original Paper
Babashkina, Maria G.
Frontera, Antonio
Kertman, Alexander V.
Saygideger, Yasemin
Murugavel, Swaminathan
Safin, Damir A.
Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study
title Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study
title_full Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study
title_fullStr Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study
title_full_unstemmed Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study
title_short Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study
title_sort favipiravir: insight into the crystal structure, hirshfeld surface analysis and computational study
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189275/
http://dx.doi.org/10.1007/s13738-021-02285-x
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