Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of Counterion
The study of the formation of microstructures during the interaction of a protonated drug-like compound (API) with a maleic acid monoanion sheds light on the assembly processes in an aqueous solution at the molecular level. Molecular dynamics (MD) simulations coupled with density functional theory (...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/11/6302 |
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| author | Mikhail V. Vener Denis E. Makhrov Alexander P. Voronin Daria R. Shalafan |
| author_facet | Mikhail V. Vener Denis E. Makhrov Alexander P. Voronin Daria R. Shalafan |
| author_sort | Mikhail V. Vener |
| collection | DOAJ |
| description | The study of the formation of microstructures during the interaction of a protonated drug-like compound (API) with a maleic acid monoanion sheds light on the assembly processes in an aqueous solution at the molecular level. Molecular dynamics (MD) simulations coupled with density functional theory (DFT) calculations made it possible to find initial hydrogen bonding motifs during the assembly process, leading to the formation of heterodimers and trimers. The process of trimer formation [protonated API—maleic acid monoanion—protonated API] proceeds through the formation of three intermolecular H-bonds by the CO<sub>2</sub><sup>−</sup> group of the maleic acid monoanion in both systems. The total enthalpy/energy of these H-bonds is more than 70 kJ/mol. Thus, the maleic acid monoanion plays a key role in the processes of association in aqueous solution, and the interaction of the maleic acid monoanion with API is more preferable than the interaction of API molecules with each other. DFT computations in the discrete continuum approximation reveal the spectral features of heterodimers and trimers, and the ATR-IR spectra confirmed these findings. MD simulations followed by DFT calculations made it possible to describe the initial stages of the formation of pharmaceutical cocrystals in an aqueous solution. |
| first_indexed | 2024-03-10T01:13:36Z |
| format | Article |
| id | doaj.art-d5958744fb414ddba0cf501e56de8ac2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:13:36Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d5958744fb414ddba0cf501e56de8ac22023-11-23T14:13:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012311630210.3390/ijms23116302Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of CounterionMikhail V. Vener0Denis E. Makhrov1Alexander P. Voronin2Daria R. Shalafan3Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninskii prosp. 31, 119991 Moscow, RussiaFaculty of Natural Science, Mendeleev University of Chemical Technology, Miusskaya Square 9, 125047 Moscow, RussiaG.A. Krestov Institute of Solution Chemistry RAS, 153045 Ivanovo, RussiaG.A. Krestov Institute of Solution Chemistry RAS, 153045 Ivanovo, RussiaThe study of the formation of microstructures during the interaction of a protonated drug-like compound (API) with a maleic acid monoanion sheds light on the assembly processes in an aqueous solution at the molecular level. Molecular dynamics (MD) simulations coupled with density functional theory (DFT) calculations made it possible to find initial hydrogen bonding motifs during the assembly process, leading to the formation of heterodimers and trimers. The process of trimer formation [protonated API—maleic acid monoanion—protonated API] proceeds through the formation of three intermolecular H-bonds by the CO<sub>2</sub><sup>−</sup> group of the maleic acid monoanion in both systems. The total enthalpy/energy of these H-bonds is more than 70 kJ/mol. Thus, the maleic acid monoanion plays a key role in the processes of association in aqueous solution, and the interaction of the maleic acid monoanion with API is more preferable than the interaction of API molecules with each other. DFT computations in the discrete continuum approximation reveal the spectral features of heterodimers and trimers, and the ATR-IR spectra confirmed these findings. MD simulations followed by DFT calculations made it possible to describe the initial stages of the formation of pharmaceutical cocrystals in an aqueous solution.https://www.mdpi.com/1422-0067/23/11/6302classical MD simulationsDFT computationsATR-IR spectroscopyintra- and intermolecular hydrogen bondsmulticomponent organic crystals |
| spellingShingle | Mikhail V. Vener Denis E. Makhrov Alexander P. Voronin Daria R. Shalafan Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of Counterion International Journal of Molecular Sciences classical MD simulations DFT computations ATR-IR spectroscopy intra- and intermolecular hydrogen bonds multicomponent organic crystals |
| title | Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of Counterion |
| title_full | Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of Counterion |
| title_fullStr | Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of Counterion |
| title_full_unstemmed | Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of Counterion |
| title_short | Molecular Dynamics Simulation of Association Processes in Aqueous Solutions of Maleate Salts of Drug-like Compounds: The Role of Counterion |
| title_sort | molecular dynamics simulation of association processes in aqueous solutions of maleate salts of drug like compounds the role of counterion |
| topic | classical MD simulations DFT computations ATR-IR spectroscopy intra- and intermolecular hydrogen bonds multicomponent organic crystals |
| url | https://www.mdpi.com/1422-0067/23/11/6302 |
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