Interaction of Ca²⁺ with uracil and its thio derivatives in the gas phase

The structures and relative stabilities of the complexes formed by uracil and its sulfur derivatives, namely, 2-thio-, 4-thio, and 2,4-dithio-uracil when interacting with Ca²⁺ in the gas phase have been analyzed by means of density functional theory (DFT) calculations carried out at the B3LYP/6-311++G(3df,2p)//B3LYP/6-31+G(d,p) level. For uracil and 2,4-dithiouracil, where the two basic sites are the same, Ca²⁺ attachment to the heteroatom at position 4 is preferred. However, for the systems where both types of basic centers, a carbonyl or a thiocarbonyl group, are present, Ca²⁺-oxygen association is favored. The most stable complexes correspond to structures with Ca²⁺ bridging between the heteroatom at position 2 of the 4-enol (or the 4-enethiol) tautomer and the dehydrogenated ring nitrogen, N3. The enhanced stability of these enolic forms is two-fold, on the one hand Ca²⁺ interacts with two basic sites and on the other triggers a significant aromatization of the ring. Besides, Ca ²⁺ association has a clear catalytic effect on the tautomerization processes which connect the oxo-thione forms with the enol-enethiol tautomers. Hence, although the enol-enethiol tautomers of uracil and its thio derivatives should not be observed in the gas phase, the corresponding Ca²⁺ complexes are the most stable species and should be accessible, because the tautomerization barriers are smaller than the Ca²⁺ binding energies.