Theoretical Studies on the Binding of Cd2+ to Uracil and Its Thio-derivatives

The interaction of Cd2+ with uracil, 2-thiouracil, 4-thiouracil and 2,4-dithiouracil have been investigated by the density functional theory (DFT) calculations. For uracil and 2,4-dithiouracil, where the two basic sites are the same, Cd2+ attachment to the heteroatom at position 4 is preferred. However, for the systems where both types of basic centers, a carbonyl and a thiocarbonyl groups, are present, Cd2+ association with sulfur is favorable. The enhanced stability of these enolic and thiol forms comes from Cd2+ interaction with two basic sites simultaneously, which thereby triggers a significant aromatization of the ring. More significantly, the Cd2+ binding energy with uracil and its thio-derivatives is larger than the tautomerization barriers connecting the diketo-like forms with the corresponding enolic-like tautomers. Consequently, when associated with Cd2+, all tautomers are energetically accessible and should be observed in the gas phase.