How hydrogen bonding amplifies isomeric differences in pyridones toward strong changes in acidity and tautomerism
- 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 multipleSteric 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.…
Author details: | Robby BüchnerORCiDGND, Mattis FondellORCiD, Eric Johnn MascarenhasORCiD, Annette PietzschORCiD, Vinícius Vaz da CruzORCiD, Alexander FöhlischORCiDGND |
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DOI: | https://doi.org/10.1021/acs.jpcb.0c10873 |
ISSN: | 1520-6106 |
ISSN: | 1520-5207 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/33562959 |
Title of parent work (English): | The journal of physical chemistry : B, Condensed matter, materials, surfaces, interfaces & biophysical chemistry |
Publisher: | American Chemical Society |
Place of publishing: | Washington |
Publication type: | Article |
Language: | English |
Date of first publication: | 2021/04/09 |
Publication year: | 2021 |
Release date: | 2023/11/08 |
Volume: | 125 |
Issue: | 9 |
Number of pages: | 8 |
First page: | 2372 |
Last Page: | 2379 |
Funding institution: | ERC-ADG-2014, Advanced Investigator Grant under the Horizon 2020 EU Framework Program for Research and Innovation [669531 EDAX] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Physik und Astronomie |
DDC classification: | 5 Naturwissenschaften und Mathematik / 53 Physik / 530 Physik |
5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften | |
Peer review: | Referiert |
Publishing method: | Open Access / Hybrid Open-Access |
License (German): | CC-BY-NC-ND - Namensnennung, nicht kommerziell, keine Bearbeitungen 4.0 International |