Theoretical study on the intramolecular proton transfer reactions of 3-methyl-5-hydroxyisoxazole and its water complexes

Ma, Yufang; Pei, Kemei; Zheng, Xuming

doi:10.1016/j.theochem.2007.06.012

Cited by 1 publication

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other work on β-diketones and related molecules is largely consistent with the observations of Yamabe et al 26,27 In general, inclusion of a single reactive water lowers the barrier by 30-40 kcal/mol for typical molecules, a second reactive water lowers the barrier a further 8-18 kcal/mol, and each of the first two solvating waters can lower the barrier by up to ~7 kcal/mol; diminishing effects are observed for further incremental solvent waters. 21,23,26 Cucinotta et al applied an ab initio metadynamics treatment to keto-enol tautomerization of acetone in an aqueous solution consisting of 28 water molecules.…”

Section: Introductionsupporting

confidence: 85%

“…Keto–enol tautomerization plays a fundamental role in many organic and biochemical reactions as the activated C–C double bond of the enol form is a useful target for nucleophilic attack. The thermodynamics of reaction has been studied extensively with both experiment − and theory, ,− which are generally in agreement; either of the two tautomers may be favored depending on the compound and solvation conditions (more extensive reference lists can be found in refs and ). The role of water molecules and acid catalysts in the tautomerization mechanism has been studied less extensively.…”

Section: Introductionmentioning

confidence: 94%

“…The role of water molecules and acid catalysts in the tautomerization mechanism has been studied less extensively. Theoretical studies have shown that the reaction barrier varies substantially with the number and placement of participating waters. ,− However, despite significant advances, ,− the level of solvation required to realistically model keto–enol tautomerization has not been fully established. It is not known whether extensive hydrogen bonding water networks that can significantly reduce the barrier in small water clusters are highly sampled in solution at thermal equilibrium.…”

Section: Introductionmentioning

confidence: 99%

“…This paper addresses these aspects of keto–enol tautomerization. Previous work on limited solvation evaluated the enthalpic contribution to the tautomerization reaction barrier for reactions involving proton-transfer chains of up to four waters. ,− We focus on proton-transfer chains up to two waters in length and compare the influence of solvation in a limited solvation environment and in a fully solvated environment representative of thermal equilibrium at 300 K. We expect the results to be relevant for proton-transfer chains of various lengths.…”

Section: Introductionmentioning

confidence: 99%

“…With the exception of the metadynamics work, previous studies focused on optimized structures with up to five waters distributed between reactive and solvating roles. ,, It has yet to be established whether this degree of hydration is sufficient to reproduce solution-phase barrier heights or reaction mechanisms or indeed whether it is possible to do so within a minimum-energy path (MEP) conceptual framework. Fully optimized water hydrogen bond networks might represent events so extremely rare that they are not predictive of the observed kinetics in solution at ambient temperatures.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Theoretical Study of HOCl-Catalyzed Keto–Enol Tautomerization of β-Cyclopentanedione in an Explicit Water Environment

2013

View full text Add to dashboard Cite

The mechanism of acid-catalyzed keto-enol tautomerization of β-cyclopentanedione (CPD) in solution is studied computationally. Reaction profiles are first calculated for a limited solvation environment using ab initio and density functional methods. Barrier heights for systems including up to one hydration shell of explicit water molecules depend strongly on the number of waters involved in proton transfer, and to a lesser but significant extent on the number of waters forming hydrogen bonds with waters in the proton transfer chain (each such water reduces the barrier by 4.4 kcal/mol on average). Barriers of 8-13 kcal/mol were obtained when a full or nearly full hydration shell was present, consistent with calculations for non-acid-catalyzed keto-enol tautomerization of related molecules. The presence of HOCl reduced the barrier by 4.5 kcal/mol viz-a-viz the gas phase, consistent with the well-known principle that keto-enol tautomerization can be acid or base catalyzed. Reaction was also modeled beginning with snapshots of reactant conformations taken from a 300 K molecular dynamics simulation of CPD, HOCl and 324 explicit waters. Reaction profiles were calculated at a QM/MM level with waters in the first hydration shell either fixed or energy minimized at each step along the reaction coordinate. A substantial variation in barrier height was observed in both cases, depending primarily on electrostatic interactions (hydrogen bonding) with first-hydration-shell waters and to a lesser extent on electrostatic interactions with more distant waters and geometric distortion effects. For the lowest barriers, the extent of barrier reduction by waters involved in proton transfer is consistent with the limited-solvation results, but further barrier reduction due to hydrogen-bonding to waters involved in proton transfer is not observed. It is postulated that this is because highly flexible structures such as extensive hydrogen bonding networks optimal for reaction are entropically disfavored and so may not contribute significantly to the observed reaction rate.

show abstract