Buchner, R.; Fondell, M.; Mascarenhas, E.J.; Pietzsch, A.; Vaz da Cruz, V.; Fohlisch, A.: How Hydrogen Bonding Amplifies Isomeric Differences in Pyridones toward Strong Changes in Acidity and Tautomerism. The Journal of Physical Chemistry B 125 (2021), p. 2372–2379
10.1021/acs.jpcb.0c10873
Open Access Version (externer Anbieter)
Abstract:
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.