Computational Study of Proton Transfer in Tautomers of 3‐ and 5‐Hydroxypyrazole Assisted by Water

Abstract

The tautomerism of 3- and 5-hydroxypyrazole is studied at the B3LYP, CCSD and G3B3 computational levels, including the gas phase, PCM-water effects, and proton transfer assisted by water molecules. To understand the propensity of tautomerization, hydrogen-bond acidity and basicity of neutral species is approached by means of correlations between donor/acceptor ability and H-bond interaction energies. Tautomerism processes are highly dependent on the solvent environment, and a significant reduction of the transition barriers upon solvation is seen. In addition, the inclusion of a single water molecule to assist proton transfer decreases the barriers between tautomers. Although the second water molecule further reduces those barriers, its effect is less appreciable than the first one. Neutral species present more stable minima than anionic and cationic species, but relatively similar transition barriers to anionic tautomers.

Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazoles

“…As stated by El-Sattar et al, the chemical potential of a compound reflects the relationship between its structure and reactivity, thus a comparatively higher chemical potential of a compound means a higher reactivity [115]. In compounds that exhibit tautomerism, the reactivity may be controlled by a particular tautomeric form and, according to the Gustafsson paradox, the less abundant tautomer tends to be the most reactive one [116]. In these circumstances, a paramount need to elucidate the precise chemical potential of the entities present in a specific reactant mixture emerges.…”

Solvent and Substituent Effects on the Phosphine + CO2 Reaction

“…In the field of solvent effects there are specific and bulky effects. The specific effects are due to weak interactions, mainly hydrogen bonds, which are theoretically studied building up supramolecules, for instance, proton transfer in pyrazoles being assisted by two linked water molecules [1][2][3]. The general solvent effects consider the solvent as bulk and are studied empirically using solvent scales (Kamlet et al [4], Reichardt [5], Abraham [6], Catalán [7]), as well as theoretically using the polarizable continuum model, PCM (Tomasi et al [8]), the conductor-like screening model, COSMO (Orozco and Luque [9]), and Density Functional Solvation Model, DGSOL (Zhu et al [10]).…”

A Full QM Computational Study of the Catalytic Mechanism of α‐1,4‐Glucan Lyases

“…To verify this hypothesis, we investigated at the same computational level the tautomerization process enol‐AF→keto‐AF outside of the protein environment. In our model the proton transfer was “assisted” by a water molecule (explicitly considered) in aqueous solvent (PCM computations) . We found an activation energy barrier of 35.8 kcal mol −1 (see Figure S3 in the Supplementary material).…”

“…In our model the proton transfer was "assisted" by a water molecule (explicitly considered) in aqueous solvent (PCM computations). [49] We found an activation energy barrier of 35.8 kcal mol À1 (see Figure S3 in the Supplementary material). Thus, it seems more reasonable to hypothesize that enol-AF undergoes the tautomerization process inside the enzyme before leaving the active site rather than in the aqueous solution.…”