13C-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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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-09, Vol.27 (19), p.6268
Main Authors: García-Báez, Efrén V., Padilla-Martínez, Itzia I., Cruz, Alejandro, Rosales-Hernández, Martha C.
Format: Article
Language:English
Subjects:
13C NMR
Benzimidazoles
Binding
Bioactive compounds
Biological activity
Carbon
Chemical equilibrium
Equilibrium
Hydrocarbons
mesomery
Nitrogen
NMR
Nuclear magnetic resonance
Proteins
pyridine nitrogen atom
pyrrole nitrogen atom
Review
Solvents
Spectrum analysis
tautomeric equilibrium
Tautomers
Therapeutic applications
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Summary: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 13C-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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27196268