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How Hydrogen Bonding Amplifies Isomeric Differences in Pyridones toward Strong Changes in Acidity and Tautomerism

[Image: see text] Steric hindrance of hydration and hydrogen bond enhancement by localized charges have been identified as key factors for the massive chemical differences between the hydroxypyridine/pyridone isomers in aqueous solution. While all isomers occur mainly in the hydroxypyridine form in...

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Detalles Bibliográficos
Autores principales: Büchner, Robby, Fondell, Mattis, Mascarenhas, Eric J., Pietzsch, Annette, Vaz da Cruz, Vinícius, Föhlisch, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957858/
https://www.ncbi.nlm.nih.gov/pubmed/33562959
http://dx.doi.org/10.1021/acs.jpcb.0c10873
Descripción
Sumario:[Image: see text] Steric hindrance of hydration and hydrogen bond enhancement by localized charges have been identified as key factors for the massive chemical differences between the hydroxypyridine/pyridone isomers in aqueous solution. While all isomers occur mainly in the hydroxypyridine form in the gas phase, they differ by more than 3 orders of magnitude both in their acidity and tautomeric equilibrium constants upon hydration. By monitoring the electronic and solvation structures as a function of the protonation state and the O(–) substitution position on the pyridine ring, the amplification of the isomeric differences in aqueous solution has been investigated. Near-edge X-ray absorption fine structure (NEXAFS) measurements at the N K-edge served as the probe of the chemical state. The combination of molecular dynamics simulations, complete active space self-consistent field (CASSCF), and time-dependent density functional theory (TD-DFT) spectral calculations contributes to unraveling the principles of tautomerism and acidity in multiple biochemical systems based on tautomerism.