<sup>13</sup>C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion
Benzimidazole is an important heterocyclic fragment, present in many biologically active compounds with a great variety of therapeutic purposes. Most of the benzimidazole activities are explained through the existence of 1,3-tautomeric equilibrium. As the binding affinity of each tautomer to a prote...
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MDPI AG
2022-09-01
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| author | Efrén V. García-Báez Itzia I. Padilla-Martínez Alejandro Cruz Martha C. Rosales-Hernández |
| author_facet | Efrén V. García-Báez Itzia I. Padilla-Martínez Alejandro Cruz Martha C. Rosales-Hernández |
| author_sort | Efrén V. García-Báez |
| collection | DOAJ |
| description | Benzimidazole is an important heterocyclic fragment, present in many biologically active compounds with a great variety of therapeutic purposes. Most of the benzimidazole activities are explained through the existence of 1,3-tautomeric equilibrium. As the binding affinity of each tautomer to a protein target depends on an established bioactive conformation, the effect of tautomers on the ligand protein binding mechanism is determinant. In this work, we searched and analyzed a series of reported <sup>13</sup>C-NMR spectra of benzazoles and benzazolidine-2-thiones with the purpose of estimating their tautomeric equilibrium. Herein, several approaches to determine this problem are presented, which makes it a good initial introduction to the non-expert reader. This chemical shift difference and C4/C7 signals of benzimidazolidine-2-thione and 1-methyl-2-thiomethylbenzimidazole as references were used in this work to quantitatively calculate, in solution, the pyrrole–pyridine tautomeric ratio in equilibrium. The analysis will help researchers to correctly assign the chemical shifts of benzimidazoles and to calculate their intracyclic or exocyclic tautomeric ratio as well as mesomeric proportion in benzimidazoles. |
| first_indexed | 2024-03-09T21:25:55Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:25:55Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-ade2c708183a491ea4c46cac15fbf23b2023-11-23T21:08:33ZengMDPI AGMolecules1420-30492022-09-012719626810.3390/molecules27196268<sup>13</sup>C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio CriterionEfrén V. García-Báez0Itzia I. Padilla-Martínez1Alejandro Cruz2Martha C. Rosales-Hernández3Laboratorio de Química Supramolecular y Nanociencias, Instituto Politécnico Nacional-UPIBI, Av. Acueducto s/n, Barrio la Laguna Ticomán, Mexico City 07340, MexicoLaboratorio de Química Supramolecular y Nanociencias, Instituto Politécnico Nacional-UPIBI, Av. Acueducto s/n, Barrio la Laguna Ticomán, Mexico City 07340, MexicoLaboratorio de Química Supramolecular y Nanociencias, Instituto Politécnico Nacional-UPIBI, Av. Acueducto s/n, Barrio la Laguna Ticomán, Mexico City 07340, MexicoLaboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Mexico City 11340, MexicoBenzimidazole is an important heterocyclic fragment, present in many biologically active compounds with a great variety of therapeutic purposes. Most of the benzimidazole activities are explained through the existence of 1,3-tautomeric equilibrium. As the binding affinity of each tautomer to a protein target depends on an established bioactive conformation, the effect of tautomers on the ligand protein binding mechanism is determinant. In this work, we searched and analyzed a series of reported <sup>13</sup>C-NMR spectra of benzazoles and benzazolidine-2-thiones with the purpose of estimating their tautomeric equilibrium. Herein, several approaches to determine this problem are presented, which makes it a good initial introduction to the non-expert reader. This chemical shift difference and C4/C7 signals of benzimidazolidine-2-thione and 1-methyl-2-thiomethylbenzimidazole as references were used in this work to quantitatively calculate, in solution, the pyrrole–pyridine tautomeric ratio in equilibrium. The analysis will help researchers to correctly assign the chemical shifts of benzimidazoles and to calculate their intracyclic or exocyclic tautomeric ratio as well as mesomeric proportion in benzimidazoles.https://www.mdpi.com/1420-3049/27/19/6268benzimidazoles<sup>13</sup>C NMRtautomeric equilibriummesomerypyridine nitrogen atompyrrole nitrogen atom |
| spellingShingle | Efrén V. García-Báez Itzia I. Padilla-Martínez Alejandro Cruz Martha C. Rosales-Hernández <sup>13</sup>C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion Molecules benzimidazoles <sup>13</sup>C NMR tautomeric equilibrium mesomery pyridine nitrogen atom pyrrole nitrogen atom |
| title | <sup>13</sup>C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion |
| title_full | <sup>13</sup>C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion |
| title_fullStr | <sup>13</sup>C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion |
| title_full_unstemmed | <sup>13</sup>C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion |
| title_short | <sup>13</sup>C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion |
| title_sort | sup 13 sup c nmr chemical shifts in 1 3 benzazoles as a tautomeric ratio criterion |
| topic | benzimidazoles <sup>13</sup>C NMR tautomeric equilibrium mesomery pyridine nitrogen atom pyrrole nitrogen atom |
| url | https://www.mdpi.com/1420-3049/27/19/6268 |
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