The effect of water-mediated catalysis on the intra­molecular proton-transfer reactions of the isomers of 5-chloro­uracil: a theoretical study

The geometrical structures and thermal energies (E), enthalpies (H) and Gibbs free energies (G) of 13 isomers of 5-chloro­uracil (5ClU) in the gas and water phases were investigated using the density functional theory (DFT) method at the M06-2X/6-311++g(3df,3pd) level. The isomers of 5ClU can be micro­hydrated at different mol­ecular target sites. The mono- and dihydrated forms are the most stable in both the gas and water phases, and, because of the inter­molecular inter­actions, the hydrations lead to a degree of change in the stability trend. Two types of isomerizations were considered: the inter­nal H—O bond rotations in which the H atom rotates 180° around the C—O bond and the intra­molecular proton-transfer reactions in which an H atom is transferred between an O atom and a neighbouring N atom. The forward and backward energy barriers for isomerizations of nonhydrated 5ClU were calculated. In addition, 16 optimized transition-state structures for water-mediated catalysis on isomerizations of 5ClU were investigated. The forward and backward proton-transfer energy barriers of water-mediated catalysis on isomerizations of 5ClU were obtained. The results indicate that the catalytic effect of two H₂O mol­ecules is much greater than that of one H₂O mol­ecule in isomerizations of 5ClU.