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

J Comput Aided Mol Des. 2015 Feb;29(2):143-54. doi: 10.1007/s10822-014-9810-7. Epub 2014 Dec 16.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Benzimidazoles / chemistry*
  • Isomerism
  • Magnetic Resonance Spectroscopy
  • Photons
  • Solutions / chemistry*

Substances

  • Benzimidazoles
  • Solutions
  • benzimidazole