The catalytic effect of water on the keto-enol tautomerism. Pyruvate and acetylacetone: a computational challenge

The catalytic effect of explicit water molecules on the keto-enol tautomerism in a system of biological interest (enolpyruvate) has been investigated at the B3LYP/6-31++G** level by exploring the potential energy surface in the presence of 1 or 2 water molecules and comparing the energy profiles to the direct tautomerisation one. The water-assisted mechanisms turned out to be more favourable than the direct ones, in agreement with what occurred for the acetylacetone tautomerism in the presence of a single water molecule. To compare the behaviour of water in pyruvate and in acetylacetone, the two-water-assisted mechanism has been also examined for the latter at the B3LYP/6-31G* level. A number of stationary points for both compounds in vacuo and in the presence of explicit water molecules have been computed with DFT coupled to larger basis sets and at the MP2 level. Two diketo forms more stable than any of the keto-enol tautomers have been located, while for pyruvate the keto form is always more favourable than the enol one. The equilibrium constant for acetylacetone tautomerisation has been computed with high accuracy, performing a complete basis set extrapolation for the relative internal energy, to determine whether the quality of the method/basis set is responsible for the earlier modest agreement with the experimental value. Monte Carlo and molecular dynamics simulations helped characterize the solution structure and association features in the 0.03-0.22 molar concentration range.