Prototype of the Heteroaromatic Tautomers: 2-Pyridone / 2-Hydroxypyridine

In this work, we review the theoretical/experimental study progress in the classic case of a tautomeric equilibrium, 2-pyridone/2-hydroxypyridine (2-PY/2-HY), as well as original research on tautomerization reaction energetics. Our work sheds light on a matter of investigation which lasts more than a century, a challenge to the reliability of the quantum methods, especially to DFT. Our results reveal the responsible for the notable contrast between the relative stability order estimation by wavefunction (WF) and density functional (DFT) methods: The Koopmans’ theorem. Among the results by Hartree-Fock, QCISD and 127 DFT functionals, our work extends on one LC functional. The estimation of the relative stability is in excellent agreement with experiments. The analogous approach for other tautomeric compounds corroborates the reliability of our description and its potential application, e.g., on the development of the molecular switches, computer-aided drug design, and new DFT functionals.