Computational Estimation of the Acidities of Pyrimidines and Related Compounds
Pyrimidines are key components in the genetic code of living organisms and the pyrimidine scaffold is also found in many bioactive and medicinal compounds. The acidities of these compounds, as represented by their pK<sub>a</sub>s, are of special interest since they determine the species...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/2/385 |
| _version_ | 1797491544974950400 |
|---|---|
| author | Rachael A. Holt Paul G. Seybold |
| author_facet | Rachael A. Holt Paul G. Seybold |
| author_sort | Rachael A. Holt |
| collection | DOAJ |
| description | Pyrimidines are key components in the genetic code of living organisms and the pyrimidine scaffold is also found in many bioactive and medicinal compounds. The acidities of these compounds, as represented by their pK<sub>a</sub>s, are of special interest since they determine the species that will prevail under different pH conditions. Here, a quantum chemical quantitative structure–activity relationship (QSAR) approach was employed to estimate these acidities. Density-functional theory calculations at the B3LYP/6-31+G(d,p) level and the SM8 aqueous solvent model were employed, and the energy difference ∆E<sub>H2O</sub> between the parent compound and its dissociation product was used as a variation parameter. Excellent estimates for both the cation → neutral (pK<sub>a1</sub>, R<sup>2</sup> = 0.965) and neutral → anion (pK<sub>a2</sub>, R<sup>2</sup> = 0.962) dissociations were obtained. A commercial package from Advanced Chemical Design also yielded excellent results for these acidities. |
| first_indexed | 2024-03-10T00:50:51Z |
| format | Article |
| id | doaj.art-4bda0aa2bb27465bb38b3d4230463dba |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T00:50:51Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4bda0aa2bb27465bb38b3d4230463dba2023-11-23T14:51:09ZengMDPI AGMolecules1420-30492022-01-0127238510.3390/molecules27020385Computational Estimation of the Acidities of Pyrimidines and Related CompoundsRachael A. Holt0Paul G. Seybold1Department of Chemistry, Wright State University, Dayton, OH 45435, USADepartment of Chemistry, Wright State University, Dayton, OH 45435, USAPyrimidines are key components in the genetic code of living organisms and the pyrimidine scaffold is also found in many bioactive and medicinal compounds. The acidities of these compounds, as represented by their pK<sub>a</sub>s, are of special interest since they determine the species that will prevail under different pH conditions. Here, a quantum chemical quantitative structure–activity relationship (QSAR) approach was employed to estimate these acidities. Density-functional theory calculations at the B3LYP/6-31+G(d,p) level and the SM8 aqueous solvent model were employed, and the energy difference ∆E<sub>H2O</sub> between the parent compound and its dissociation product was used as a variation parameter. Excellent estimates for both the cation → neutral (pK<sub>a1</sub>, R<sup>2</sup> = 0.965) and neutral → anion (pK<sub>a2</sub>, R<sup>2</sup> = 0.962) dissociations were obtained. A commercial package from Advanced Chemical Design also yielded excellent results for these acidities.https://www.mdpi.com/1420-3049/27/2/385pyrimidinesaciditiespK<sub>a</sub>density-functional theoryQSAR |
| spellingShingle | Rachael A. Holt Paul G. Seybold Computational Estimation of the Acidities of Pyrimidines and Related Compounds Molecules pyrimidines acidities pK<sub>a</sub> density-functional theory QSAR |
| title | Computational Estimation of the Acidities of Pyrimidines and Related Compounds |
| title_full | Computational Estimation of the Acidities of Pyrimidines and Related Compounds |
| title_fullStr | Computational Estimation of the Acidities of Pyrimidines and Related Compounds |
| title_full_unstemmed | Computational Estimation of the Acidities of Pyrimidines and Related Compounds |
| title_short | Computational Estimation of the Acidities of Pyrimidines and Related Compounds |
| title_sort | computational estimation of the acidities of pyrimidines and related compounds |
| topic | pyrimidines acidities pK<sub>a</sub> density-functional theory QSAR |
| url | https://www.mdpi.com/1420-3049/27/2/385 |
| work_keys_str_mv | AT rachaelaholt computationalestimationoftheaciditiesofpyrimidinesandrelatedcompounds AT paulgseybold computationalestimationoftheaciditiesofpyrimidinesandrelatedcompounds |