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

Herein, we present a simple and versatile theo- retical-experimental approach to assess the tautomeric distribution on 5(6)-aminobenzimidazole (5(6)-ABZ) deriv- atives 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 per- formance for B3LYP and PBE0. The direct test of the pro- posed 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.