A computational study of intramolecular hydrogen bonds breaking/formation: impact on the structural flexibility of the ranitidine molecule

Abstract

Ranitidine is a histamine H2-receptor antagonist that reduces gastric acid secretion. We studied the flexibility of the ranitidine molecule with the special focus on the network of diverse intramolecular hydrogen bonds: N-H ⋯O, N-H ⋯N, C-H ⋯O, C-H ⋯N and N-H ⋯S. We performed static density functional theory calculations of global and local minima and analyzed their stability at finite temperature in the Car–Parrinello molecular dynamics simulations. We observed intramolecular H-bonds breaking/formation crucial for the structural rearrangements leading to the folding process. The lifetimes of the closed structures of ranitidine were also estimated. The existence of hydrogen bonds and their strength were confirmed on the basis of topological parameters in the bond critical points utilizing Quantum Theory of Atoms in Molecules.

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Acknowledgments

One of the authors of the publication, Mariana Kozlowska, is a beneficiary of the project “Scholarship for PhD students of Podlaskie Voivodeship”. The project is co-financed by European Social Fund, Polish Government and Podlaskie Voivodeship.

All calculations were performed at the Interdisciplinary Centre for Mathematical and Computational Modelling (ICM) at Warsaw University under a grant No. G55-1.

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Correspondence to Mariana Kozlowska.

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Kozlowska, M., Goclon, J. & Rodziewicz, P. A computational study of intramolecular hydrogen bonds breaking/formation: impact on the structural flexibility of the ranitidine molecule. J Mol Model 21, 94 (2015). https://doi.org/10.1007/s00894-015-2591-7

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Keywords

  • Ranitidine
  • Intramolecular hydrogen bonds
  • AIM analysis
  • Car-Parrinello molecular dynamics
  • Structural flexibility