Analysis reveals proton transfer characteristics in pseudocycles, highlighting limitations of density functional methods.
Intramolecular hydrogen bonds forming small pseudocycles (Cn) present significant theoretical challenges. The most critical cases are C4 and C6 motifs. In asymmetric systems, different tautomers can be nearly isoenergetic. In both symmetric and asymmetric frameworks, proton-transfer barriers vary strongly with geometry and electronic structure. Standard density functional methods often fail to reproduce these features with quantitative accuracy. To address this, we investigated representative systems including 2-pyridone/2-hydroxypyridine, 2-thiopyridone/2-mercaptopyridine, 2-aminopyridine, malonaldehyde, thiomalonaldehyde, and tropolone. Our results show that benchmark accuracy at affordable cost can be achieved by combining explicitly correlated coupled-cluster treatments for valence correlation, inclusion of core–valence correlation, and DFT-based evaluation of vibrational contributions and rovibrational couplings. This strategy provides a robust benchmark for assessing density functionals and guiding the development of improved theoretical models.
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Fiore et al. (2025) studied this question.
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