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

Abstract

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.