Reaction Mechanism and Tautomeric Equilibrium of 2-Mercaptopyrimidine in the Gas Phase and in Aqueous Solution:  A Combined Monte Carlo and Quantum Mechanics Study

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Vol. 110; no. 22; pp. 7253 - 7261
• Main Authors: Lima, Maria Carolina P, Coutinho, Kaline, Canuto, Sylvio, Rocha, Willian R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 08.06.2006
• Subjects: Gases - chemistry; Molecular Structure; Monte Carlo Method; Pyrimidines - chemistry; Quantum Theory; Solutions - chemistry; Stereoisomerism; Thermodynamics; Water - chemistry
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/jp060821b

A combined Monte Carlo and quantum mechanical study was carried out to analyze the tautomeric equilibrium of 2-mercaptopyrimidine in the gas phase and in aqueous solution. Second- and fourth-order Møller−Plesset perturbation theory calculations indicate that in the gas phase thiol (Pym-SH) is more stable than the thione (Pym-NH) by ca. 8 kcal/mol. In aqueous solution, thermodynamic perturbation theory implemented on a Monte Carlo NpT simulation indicates that both the differential enthalpy and Gibbs free energy favor the thione form. The calculated differential enthalpy is Δ H SH → NH(solv) = −1.7 kcal/mol and the differential Gibbs free energy is Δ G SH → NH(solv) = −1.9 kcal/mol. Analysis is made of the contribution of the solute−solvent hydrogen bonds and it is noted that the SH group in the thiol and NH group in the thione tautomers act exclusively as a hydrogen bond donor in aqueous solution. The proton transfer reaction between the tautomeric forms was also investigated in the gas phase and in aqueous solution. Two distinct mechanisms were considered:  a direct intramolecular transfer and a water-assisted mechanism. In the gas phase, the intramolecular transfer leads to a large energy barrier of 34.4 kcal/mol, passing through a three-center transition state. The proton transfer with the assistance of one water molecule decreases the energy barrier to 17.2 kcal/mol. In solution, these calculated activation barriers are, respectively, 32.0 and 14.8 kcal/mol. The solvent effect is found to be sizable but it is considerably more important as a participant in the water-assisted mechanism than the solvent field of the solute−solvent interaction. Finally, the calculated total Gibbs free energy is used to estimate the equilibrium constant.