On the mechanism of the mutagenic action of 5-bromouracil: A DFT study of uracil and 5-bromouracil in a water cluster

Density functional theory calculations on the canonical (keto) and rare (enol) tautomeric forms of uracil and 5-bromouracil in a cluster consisting of 50 water molecules are presented. The keto form of uracil is favored over the enol tautomer in both gas phase and solution. However, the presence of the water cluster reverses the tautomeric preference of 5-bromouracil, rendering the rare tautomeric form to be preferred over the canonical form in aqueous solution. This effect is to a large extent due to the more favorable water-water interactions in the cluster around 5-bromouracil and can therefore only be obtained by including explicit water-water interactions in the calculations.