On the protonation equilibrium for the benzimidazole derivative Hoechst 33258: an electronic molecular orbital study

Hoechst 33258 and its deprotonated forms have been examined in the gas-phase and in solution using quantum mechanical methods. Ab initio calculations at the HF level have been used to investigate the more relevant geometrical trends of such species, while proton affinities and gas-phase basicities were derived from B3LYP and MP2 electronic energies. Solvation energies were calculated using a dielectric continuum model: MST. The Delta(p)K(a) values were estimated by combining the gas-phase basicities and the free energies of solvation. Comparison of these Delta(p)K(a) values with experimentally reported data have been used to highlight the advantages and limitations of this strategy.