Effect of mono- and di-hydration on the stability and tautomerisms of different tautomers of creatinine: A thermodynamic and mechanistic study

Abstract

Relative stabilities of nine tautomers of creatinine in gas and aqueous phases and hydrated forms were studied by M062X, MP2 and B3LYP computational methods. It was found that two tautomers (an amino and an imino) have significant stability and relative abundances among all. The imino tautomer is more stable in gas phase while the amino form is more stable in aqueous phase and in di-hydrated form. The stability and relative abundances of the both amino and imino tautomers in mono-hydrated form were approximately the same. Activation energies and Gibbs free energies of isomerizations in creatinine, including intramolecular proton transfers and internal OH rotations, were calculated. The energy barriers of rotations of hydrogen atom of OH group around C–O bond were smaller than 40kJ/mol. Two types of proton transfer reactions including imine↔amine and keto↔enol tautomerisms were considered. The activation energies of keto–enol tautomerisms, in which the proton is transferred between oxygen and carbon atoms, were in the range 270–300kJ/mol. Catalysis effect of one and two water molecules on the intramolecular proton transfers was studied. It was found that the activation energies are decreased by about 130 and 150kJ/mol in the presence of one and two water molecules, respectively.