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

Abstract

The artificial nucleobase 6-pyrazolylpurine (6PP) and its deaza derivatives 1-deaza-6-pyrazolylpurine (1D6PP), 7-deaza-6-pyrazolylpurine (7D6PP), and 1,7-dideaza-6-pyrazolylpurine (1,7D6PP) 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) 7D6PP form stable silver(I)-mediated base pairs with cytosine, but not with thymine. 1D6PP and 1,7D6PP do not engage in the formation of stabilizing silver(I)-mediated base pairs with cytosine or thymine. The different behavior of 1D6PP, 7D6PP, and 1,7D6PP 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