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(13)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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Autores principales: García-Báez, Efrén V., Padilla-Martínez, Itzia I., Cruz, Alejandro, Rosales-Hernández, Martha C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570581/
https://www.ncbi.nlm.nih.gov/pubmed/36234805
http://dx.doi.org/10.3390/molecules27196268
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author García-Báez, Efrén V.
Padilla-Martínez, Itzia I.
Cruz, Alejandro
Rosales-Hernández, Martha C.
author_facet García-Báez, Efrén V.
Padilla-Martínez, Itzia I.
Cruz, Alejandro
Rosales-Hernández, Martha C.
author_sort García-Báez, Efrén V.
collection PubMed
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 (13)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.
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spelling pubmed-95705812022-10-17 (13)C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion García-Báez, Efrén V. Padilla-Martínez, Itzia I. Cruz, Alejandro Rosales-Hernández, Martha C. Molecules Review 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 (13)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. MDPI 2022-09-23 /pmc/articles/PMC9570581/ /pubmed/36234805 http://dx.doi.org/10.3390/molecules27196268 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
García-Báez, Efrén V.
Padilla-Martínez, Itzia I.
Cruz, Alejandro
Rosales-Hernández, Martha C.
(13)C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion
title (13)C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion
title_full (13)C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion
title_fullStr (13)C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion
title_full_unstemmed (13)C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion
title_short (13)C-NMR Chemical Shifts in 1,3-Benzazoles as a Tautomeric Ratio Criterion
title_sort (13)c-nmr chemical shifts in 1,3-benzazoles as a tautomeric ratio criterion
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570581/
https://www.ncbi.nlm.nih.gov/pubmed/36234805
http://dx.doi.org/10.3390/molecules27196268
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