An Accurate Approach for Computational pKa Determination of Phenolic Compounds
Computational chemistry is a valuable tool, as it allows for in silico prediction of key parameters of novel compounds, such as pKa. In the framework of computational pKa determination, the literature offers several approaches based on different level of theories, functionals and continuum solvation...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/23/8590 |
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| author | Silvia Pezzola Samuele Tarallo Alessandro Iannini Mariano Venanzi Pierluca Galloni Valeria Conte Federica Sabuzi |
| author_facet | Silvia Pezzola Samuele Tarallo Alessandro Iannini Mariano Venanzi Pierluca Galloni Valeria Conte Federica Sabuzi |
| author_sort | Silvia Pezzola |
| collection | DOAJ |
| description | Computational chemistry is a valuable tool, as it allows for in silico prediction of key parameters of novel compounds, such as pKa. In the framework of computational pKa determination, the literature offers several approaches based on different level of theories, functionals and continuum solvation models. However, correction factors are often used to provide reliable models that adequately predict pKa. In this work, an accurate protocol based on a direct approach is proposed for computing phenols pKa. Importantly, this methodology does not require the use of correction factors or mathematical fitting, making it highly practical, easy to use and fast. Above all, DFT calculations performed in the presence two explicit water molecules using CAM-B3LYP functional with 6-311G+dp basis set and a solvation model based on density (SMD) led to accurate pKa values. In particular, calculations performed on a series of 13 differently substituted phenols provided reliable results, with a mean absolute error of 0.3. Furthermore, the model achieves accurate results with -CN and -NO<sub>2</sub> substituents, which are usually excluded from computational pKa studies, enabling easy and reliable pKa determination in a wide range of phenols. |
| first_indexed | 2024-03-09T17:38:42Z |
| format | Article |
| id | doaj.art-6c4f0caf07b84663a989d72ab650c6d2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T17:38:42Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-6c4f0caf07b84663a989d72ab650c6d22023-11-24T11:44:49ZengMDPI AGMolecules1420-30492022-12-012723859010.3390/molecules27238590An Accurate Approach for Computational pKa Determination of Phenolic CompoundsSilvia Pezzola0Samuele Tarallo1Alessandro Iannini2Mariano Venanzi3Pierluca Galloni4Valeria Conte5Federica Sabuzi6Department of Chemical Science and Technologies, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Chemical Science and Technologies, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Chemical Science and Technologies, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Chemical Science and Technologies, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Chemical Science and Technologies, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Chemical Science and Technologies, University of Rome Tor Vergata, 00133 Rome, ItalyDepartment of Chemical Science and Technologies, University of Rome Tor Vergata, 00133 Rome, ItalyComputational chemistry is a valuable tool, as it allows for in silico prediction of key parameters of novel compounds, such as pKa. In the framework of computational pKa determination, the literature offers several approaches based on different level of theories, functionals and continuum solvation models. However, correction factors are often used to provide reliable models that adequately predict pKa. In this work, an accurate protocol based on a direct approach is proposed for computing phenols pKa. Importantly, this methodology does not require the use of correction factors or mathematical fitting, making it highly practical, easy to use and fast. Above all, DFT calculations performed in the presence two explicit water molecules using CAM-B3LYP functional with 6-311G+dp basis set and a solvation model based on density (SMD) led to accurate pKa values. In particular, calculations performed on a series of 13 differently substituted phenols provided reliable results, with a mean absolute error of 0.3. Furthermore, the model achieves accurate results with -CN and -NO<sub>2</sub> substituents, which are usually excluded from computational pKa studies, enabling easy and reliable pKa determination in a wide range of phenols.https://www.mdpi.com/1420-3049/27/23/8590pKacomputational pKaphenolthymoldirect approachDFT |
| spellingShingle | Silvia Pezzola Samuele Tarallo Alessandro Iannini Mariano Venanzi Pierluca Galloni Valeria Conte Federica Sabuzi An Accurate Approach for Computational pKa Determination of Phenolic Compounds Molecules pKa computational pKa phenol thymol direct approach DFT |
| title | An Accurate Approach for Computational pKa Determination of Phenolic Compounds |
| title_full | An Accurate Approach for Computational pKa Determination of Phenolic Compounds |
| title_fullStr | An Accurate Approach for Computational pKa Determination of Phenolic Compounds |
| title_full_unstemmed | An Accurate Approach for Computational pKa Determination of Phenolic Compounds |
| title_short | An Accurate Approach for Computational pKa Determination of Phenolic Compounds |
| title_sort | accurate approach for computational pka determination of phenolic compounds |
| topic | pKa computational pKa phenol thymol direct approach DFT |
| url | https://www.mdpi.com/1420-3049/27/23/8590 |
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