Barrierless inter and intramolecular proton transfer; a DFT study of tautomerism in microsolvated and protonated systems.

DFT calculations were employed to study tautomers of 2,2-di(pyrimidin-2-yl)acetic acid (DPA) in the gas phase and in the presence of water, methanol, DMSO (microsolvation models), and proton (H(+)). In the gas phase, all three tautomers were in equilibrium with each other (T2 was slightly more favorable); but, in microsolvation with protic solvent, T3 was a major isomer. Moreover, unexpectedly enough, T1 (common form of DPA) was the least stable tautomer in the gas phase, while, in the water (as solvent), T1 was the most stable one. The calculated energy values indicated a very special barrierless tautomeric system between T2 and T3. In the gas phase, ΔG(#) for T2 → T3 was only 0.30 kcal/mol, while it was 56.4 and 44.8 kcal/mol for T2 → T1 and T3 → T1, respectively. Rate constants for conversion of T2 into T3 were high in all cases, and their values in the gas phase and in the presence of water, methanol, DMSO, and proton were 3.6 × 10(12), 3.3 × 10(9), 2.7 × 10(11), 2.3 × 10(12), and 2.3 × 10(12) s(-1), respectively. All types of microsolvation slightly decreased the rate constant of this conversion. The rate constant for conversion of T2 into T1 (1,3-H shift) in the gas phase and in the presence of water, methanol, DMSO, and proton was 3.0 × 10(-29), 2.2 × 10(5), 1.1 × 10(-34), 5.2 × 10(-40), and 4.2 × 10(-26) s(-1), respectively. These values showed that only microsolvation with water strongly increased rate constants of tautomerism for T2 → T1 and this type of tautomerism was impossible in the gas phase or other microsolvation models. Although using water as the solvent enhanced rate constants of all types of tautomeric interconversions, its enhancement was less than that of microsolvation with water.