Abstract
The structures and relative stabilities of the complexes between Cu^2+^ and uracil, 2‐thiouracil, 4‐thiouracil, and 2,4‐dithiouracil were investigated by B3LYP/6‐311+G(2df,2p)//B3LYP/6‐31G* DFT calculations. In those systems in which both types of basic centers, that is, a carbonyl and a thiocarbonyl group, are present, association of Cu^2+^ with the oxygen atom is systematically favored, in contrast to what was found for the corresponding Cu^+^ complexes. This can be understood by considering that association of Cu^2+^ is immediately followed by oxidation of the base, which accumulates the negative charge at the oxygen atoms. Similarly, for 2,4‐dithiouracil the most basic site for Cu^+^ attachment is the sulfur atom at the 4‐position, while for association of Cu^2+^ it is the sulfur atom at the 2‐position. In contrast, differences between uracil–Cu^+^ and uracil–Cu^2+^ complexes are very small, and in both cases the oxygen atom at the 4‐position is the most basic. Cu^2+^ binding energies are about 4 and 1.2 times larger than Cu^+^ binding energies and proton affinities, respectively. Uracil– and thiouracil–Cu^2+^ complexes are thermodynamically unstable but kinetically stable with respect to their dissociation into uracil^.^^+^+Cu^+^ or thiouracil^.^^+^+Cu^+^. The Cu^2+^ binding energies vary with the difference between the second ionization potential of the metal and the first ionization potential of the base. regardless of the reference acid (H^+^, Cu^+^, Cu^2+^) the basicity trend is 2,4‐dithiouracil>4‐thiouracil>2‐thiouracil>uracil.