title: Reaction mechanism and tautomeric equilibrium of 2-mercaptopyrimidine in the gas phase and in aqueous solution: a combined Monte Carlo and quantum mechanics study.
abstract: 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 DeltaH(SH)(-->)(NH)(solv) = -1.7 kcal/mol and the differential Gibbs free energy is DeltaG(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.
authors.affiliation: Departamento de Química Fundamental - CCEN, Universidade Federal de Pernambuco, Cidade Universitaria, Recife, PE, Brazil.
authors.forename: Maria Carolina P
authors.initials: MC
authors.lastname: Lima
authors.forename: Kaline
authors.initials: K
authors.lastname: Coutinho
authors.forename: Sylvio
authors.initials: S
authors.lastname: Canuto
authors.forename: Willian R
authors.initials: WR
authors.lastname: Rocha
mesh_terms: D005740:Gases / Q000737:chemistry*; D015394:Molecular Structure; D009010:Monte Carlo Method; D011743:Pyrimidines / Q000737:chemistry*; D011789:Quantum Theory; D012996:Solutions / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D005740:Gases; D011743:Pyrimidines; D012996:Solutions; D014867:Water; C064001:pyrimidine-2-thiol