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Insights on molecular modeling and supramolecular arrangement of bilastine polymorphs

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Abstract

Context

The advancement in the development of second-generation drugs in the field of antihistamines represents a significant milestone in the management of allergic diseases, targeting the effects of histamine. The efficacy of bilastine in treating allergic disorders has sparked interest in investigating its polymorphism, a crucial property that impacts quality, safety, and effectiveness as per regulatory guidelines. This study examines the polymorphism of bilastine, focusing on two crystalline forms labeled as Form I and Form II. Utilizing advanced analytical techniques, the research explores the structural characteristics and molecular interactions within these forms. Geometric parameters, such as bond lengths, bond angles, and torsion angles, are examined to comprehend molecular conformations and crystal packing arrangements. Hydrogen bonding, covalent bonds, and van der Waals forces contribute to the unique supramolecular arrangements in these forms. This study provides a significant contribution to understanding bilastine’s polymorphism, offering critical insights to researchers and regulatory bodies to ensure the quality, efficacy, and safety of antihistamine products.

Methods

The molecular conformation of two bilastine forms was obtained through DFT with the exchange–correlation functional M06-2X and the 6–311 +  + G(d,p) basis set, and the results were compared with the experimental X-ray. The atomic coordinates were obtained directly from the crystalline structures, and charge transfer was also investigated using frontier molecular orbitals (HOMO and LUMO), and MEP map in order to evaluate the energies associated with charge transfers and regions of high electron affinity. The geometric and topological parameters and intermolecular interactions in the crystals were analyzed using Hirshfeld Surface.

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Acknowledgements

The authors are grateful to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa de Goiás (FAPEG). H.B. Napolitano is a CNPq fellow (grant 302904/2023-9). Theoretical calculations were carried out in the High-Performance Computing Center of the Universidade Estadual de Goiás.

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico-(CNPq), and Fundação de Amparo à Pesquisa de Goiás (FAPEG).

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Authors and Affiliations

  1. Laboratório de Novos Materiais, Universidade Evangélica de Goiás, Anápolis, GO, Brazil

    Lauriane G. Santin, Lara F. Moreira, Nathan V. C. Oliveira, Vitória L. A. Paiva, Marina R. Ribeiro, Solemar S. Oliveira & Hamilton B. Napolitano

  2. Grupo de Química Teórica E Estrutural de Anápolis, Universidade Estadual de Goiás, Anápolis, GO, Brazil

    Lauriane G. Santin & Hamilton B. Napolitano

  3. Geolab Indústria Farmacêutica, Via Principal 1B, Qd. 08 B, Anapolis, GO, Brazil

    Lara F. Moreira, Nathan V. C. Oliveira, Vitória L. A. Paiva & Marina R. Ribeiro

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  1. Lauriane G. Santin
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Contributions

A statement of contributions of the authors:

1. Introduction: Lauriane G. Santin, Lara F. Moreira, Nathan V. C. Oliveira, Vitória L. A. Paiva, Marina R. Ribeiro, Solemar S. Oliveira and Hamilton B. Napolitano.

2. Crystallographic analysis: Lara F. Moreira, Nathan V. C. Oliveira, Vitória L. A. Paiva, Marina R. Ribeiro, and Hamilton B. Napolitano.

3. Computational procedure: Lauriane G. Santin and Solemar S. Oliveira.

4. Results and discussion: Lauriane G. Santin, Lara F. Moreira, Nathan V. C. Oliveira, Vitória L. A. Paiva, Marina R. Ribeiro, Solemar S. Oliveira, and Hamilton B. Napolitano.

5. Conclusion: Lauriane G. Santin, Lara F. Moreira, Nathan V. C. Oliveira, Vitória L. A. Paiva, Marina R. Ribeiro, Solemar S. Oliveira, and Hamilton B. Napolitano.

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Correspondence to Lauriane G. Santin.

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Santin, L.G., Moreira, L.F., Oliveira, N.V.C. et al. Insights on molecular modeling and supramolecular arrangement of bilastine polymorphs. J Mol Model 30, 157 (2024). https://doi.org/10.1007/s00894-024-05951-y

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