DFT investigation on the tautomerization reaction and NBO analysis of the Acamprosate drug

The Acamprosate is a significant drug for alcohol abuse therapy, which may be an effective treatment for tinnitus, too. The Acamprosate has two possible tautomers, Keto and Enol tautomers. Each of the tautomers involves two important conformers. In this work, employing density functional theory (DFT) and handling the solvent effects with the PCM model, the structural parameters, energetic behavior, natural bond orbital analysis (NBO), as well as tautomerism mechanization of the Acamprosate are investigated in several solvents. The conformers of the Keto tautomer are more stable than the corresponding conformers of the Enol tautomer. A strong intramolecular hydrogen bond stabilizes the molecule significantly. Increasing the polarity of the solvent reduces the rate of the tautomerization of the Acamprosate by increasing the Ea of the reaction. A large HOMO-LUMO energy gap for the most stable tautomer implies high stability of the Acamprosate.