Journal of Computer-Aided Molecular Design

, Volume 29, Issue 2, pp 143–154 | Cite as

Assessment of the tautomeric population of benzimidazole derivatives in solution: a simple and versatile theoretical–experimental approach

  • Carlos Diaz
  • Ligia Llovera
  • Lorenzo Echevarria
  • Florencio E. HernándezEmail author


Herein, we present a simple and versatile theoretical–experimental approach to assess the tautomeric distribution on 5(6)-aminobenzimidazole (5(6)-ABZ) derivatives in solution via one-photon absorption. The method is based on the optimized weighted sum of the theoretical spectra of the corresponding tautomers. In this article we show how the choice of exchange-correlation functional (XCF) employed in the calculations becomes crucial for the success of the approach. After the systematic analysis of XCFs with different amounts of exact-exchange we found a better performance for B3LYP and PBE0. The direct test of the proposed method on omeprazole, a well-known 5(6)-benzimidazole based pharmacotherapeutic, demonstrate its broader applicability. The proposed approach is expected to find direct applications on the tautomeric analysis of other molecular systems exhibiting similar tautomeric equilibria.

Graphical abstract

Using a weighted sum of the corresponding individual tautomer theoretical spectra, the tautomeric population of benzimidazole derivatives in solution and at room temperature is directly determined through the theoretical–experimental fitting of the UV–Vis spectra of the tautomeric mixture at equilibrium. The reliability of the proposed method is based on the existent spectral difference between the two species.


Computational chemistry TDDFT Tautomerism Bezimidazole Omeprazole 



This work was partially supported by the National Science Foundation through Grant Number CHE-0840431. The computing time provided by STOKES ARCC is gratefully acknowledged.

Supplementary material

10822_2014_9810_MOESM1_ESM.docx (9.9 mb)
Supplementary material 1 (DOCX 10105 kb)


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Carlos Diaz
    • 1
  • Ligia Llovera
    • 2
  • Lorenzo Echevarria
    • 2
  • Florencio E. Hernández
    • 1
    • 3
    Email author
  1. 1.Department of ChemistryUniversity of Central FloridaOrlandoUSA
  2. 2.Departamento de QuímicaUniversidad Simón BolívarCaracasVenezuela
  3. 3.CREOL/The College of Optics and PhotonicsUniversity of Central FloridaOrlandoUSA

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