Metal-mediated base pairs of 5-fluorouracil with other pyrimidine bases and a phenanthroline derivative

The ability of 5-fluorouracil (F) to form metal-mediated hetero base pairs in DNA duplexes was evaluated applying the metal ions Hg(II) and Ag(I) as well as the pyrimidine residues thymine (T) and cytosine (C) and the nucleo-base surrogate 1H-imidazo[4,5-f][1,10]phenanthroline (P) as complementary nucleobases. A particular focus was placed on the question how the stabilizing effect of metal-mediated hetero base pair formation relates to that of the respective homo base pairs. Interestingly, no general correlation was observed. While F-Mⁿ⁺-T pairs exert an average stabilization compared to the homo base pairs, the stability of duplexes containing an F-Mⁿ⁺-C pair is governed by C in the case of Hg(II) and by F in the case of Ag(I). A strong sequence-dependence of the stabilizing effect was found when F pairs with P. Here, the formation of F-Ag(I)-P and P-Hg(II)-F pairs within an identical sequence context is particularly stabilizing, whereas F-Hg(II)-P and P-Ag(I)-F pairs are much less stabilizing. Apparently, the size ratio of the nucleobases involved in the metal-mediated base pair plays an important role, too. The results of this study are important for the DNA sequence design of duplexes with tailor-suited metal-mediated base pairs.