6-Pyrazolylpurine and its deaza derivatives as nucleobases for silver(I)-mediated base pairing with pyrimidines

The artificial nucleobase 6-pyrazolylpurine (6PP) and its deaza derivatives 1-deaza-6-pyrazolylpurine ((1D)6PP), 7-deaza-6-pyrazolylpurine ((7D)6PP), and 1,7-dideaza-6-pyrazolylpurine ((1,7D)6PP) were investigated with respect to their ability to differentiate between the canonical nucleobases cytosine and thymine by means of silver(I)-mediated base pairing. As shown by temperature-dependent UV spectroscopy and by circular dichroism spectroscopy, 6PP and (to a lesser extent) (7D)6PP form stable silver(I)-mediated base pairs with cytosine, but not with thymine. (1D)6PP and (1,7D)6PP do not engage in the formation of stabilizing silver(I)-mediated base pairs with cytosine or thymine. The different behavior of (1D)6PP, (7D)6PP, and (1,7D)6PP indicates that silver(I) binding occurs via the N1 position of the purine derivative, i.e. via the Watson–Crick face. The data show that 6PP is capable of differentiating between cytosine and thymine, which is potentially relevant in the context of detecting single-nucleotide polymorphisms. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00775-023-02022-0.