Solubility of paracetamol in ethanol by molecular dynamics using the extended Einstein crystal method and experiments
© 2019 Author(s). Li and co-workers [Li et al., J. Chem. Phys. 146, 214110 (2017)] have recently proposed a methodology to compute the solubility of molecular compounds from first principles, using molecular dynamics simulations. We revise and further explore their methodology that was originally ap...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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AIP Publishing
2021
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| Online Access: | https://hdl.handle.net/1721.1/135116 |
| _version_ | 1811098094007222272 |
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| author | Bellucci, Michael A Gobbo, Gianpaolo Wijethunga, Tharanga K Ciccotti, Giovanni Trout, Bernhardt L |
| author_facet | Bellucci, Michael A Gobbo, Gianpaolo Wijethunga, Tharanga K Ciccotti, Giovanni Trout, Bernhardt L |
| author_sort | Bellucci, Michael A |
| collection | MIT |
| description | © 2019 Author(s). Li and co-workers [Li et al., J. Chem. Phys. 146, 214110 (2017)] have recently proposed a methodology to compute the solubility of molecular compounds from first principles, using molecular dynamics simulations. We revise and further explore their methodology that was originally applied to naphthalene in water at low concentration. In particular, we compute the solubility of paracetamol in an ethanol solution at ambient conditions. For the simulations, we used a force field that we previously reparameterized to reproduce certain thermodynamic properties of paracetamol but not explicitly its solubility in ethanol. In addition, we have determined the experimental solubility by performing turbidity measurements using a Crystal16 over a range of temperatures. Our work serves a dual purpose: (i) methodologically, we clarify how to compute, with a relatively straightforward procedure, the solubility of molecular compounds and (ii) applying this procedure, we show that the solubility predicted by our force field (0.085 ± 0.014 in mole ratio) is in good agreement with the experimental value obtained from our experiments and those reported in the literature (average 0.0585 ± 0.004), considering typical deviations for predictions from first principle methods. The good agreement between the experimental and the calculated solubility also suggests that the method used to reparameterize the force field can be used as a general strategy to optimize force fields for simulations in solution. |
| first_indexed | 2024-09-23T17:09:48Z |
| format | Article |
| id | mit-1721.1/135116 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:09:48Z |
| publishDate | 2021 |
| publisher | AIP Publishing |
| record_format | dspace |
| spelling | mit-1721.1/1351162022-03-29T20:43:01Z Solubility of paracetamol in ethanol by molecular dynamics using the extended Einstein crystal method and experiments Bellucci, Michael A Gobbo, Gianpaolo Wijethunga, Tharanga K Ciccotti, Giovanni Trout, Bernhardt L © 2019 Author(s). Li and co-workers [Li et al., J. Chem. Phys. 146, 214110 (2017)] have recently proposed a methodology to compute the solubility of molecular compounds from first principles, using molecular dynamics simulations. We revise and further explore their methodology that was originally applied to naphthalene in water at low concentration. In particular, we compute the solubility of paracetamol in an ethanol solution at ambient conditions. For the simulations, we used a force field that we previously reparameterized to reproduce certain thermodynamic properties of paracetamol but not explicitly its solubility in ethanol. In addition, we have determined the experimental solubility by performing turbidity measurements using a Crystal16 over a range of temperatures. Our work serves a dual purpose: (i) methodologically, we clarify how to compute, with a relatively straightforward procedure, the solubility of molecular compounds and (ii) applying this procedure, we show that the solubility predicted by our force field (0.085 ± 0.014 in mole ratio) is in good agreement with the experimental value obtained from our experiments and those reported in the literature (average 0.0585 ± 0.004), considering typical deviations for predictions from first principle methods. The good agreement between the experimental and the calculated solubility also suggests that the method used to reparameterize the force field can be used as a general strategy to optimize force fields for simulations in solution. 2021-10-27T20:10:48Z 2021-10-27T20:10:48Z 2019 2019-09-13T17:07:48Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135116 en 10.1063/1.5086706 The Journal of Chemical Physics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf AIP Publishing Other repository |
| spellingShingle | Bellucci, Michael A Gobbo, Gianpaolo Wijethunga, Tharanga K Ciccotti, Giovanni Trout, Bernhardt L Solubility of paracetamol in ethanol by molecular dynamics using the extended Einstein crystal method and experiments |
| title | Solubility of paracetamol in ethanol by molecular dynamics using the extended Einstein crystal method and experiments |
| title_full | Solubility of paracetamol in ethanol by molecular dynamics using the extended Einstein crystal method and experiments |
| title_fullStr | Solubility of paracetamol in ethanol by molecular dynamics using the extended Einstein crystal method and experiments |
| title_full_unstemmed | Solubility of paracetamol in ethanol by molecular dynamics using the extended Einstein crystal method and experiments |
| title_short | Solubility of paracetamol in ethanol by molecular dynamics using the extended Einstein crystal method and experiments |
| title_sort | solubility of paracetamol in ethanol by molecular dynamics using the extended einstein crystal method and experiments |
| url | https://hdl.handle.net/1721.1/135116 |
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