5-Aza-7-deaza-2′-deoxyguanosine and 2′-Deoxycytidine Form Programmable Silver-Mediated Base Pairs with Metal Ions in the Core of the DNA Double Helix

5-Aza-7-deaza-2-deoxyguanosine (dZ) forms a silver-mediated base pair with dC. The metal ion pair represents a mimic of the H-bonded Watson-Crick dG-dC pair. The modified nucleoside displays a similar shape as the parent 2-deoxyguanosine from which it can be constructed by transposition of nitrogen-7 to the bridgehead position-5. It lacks the major groove binding site as the positional change moves the dG- acceptor position from nitrogen-7 to nitrogen-1. As a shape mimic of dG, it fits nicely in the DNA double helix. The purine-pyrimidine dZ-dC hetero pair shows a relationship to the pyrimidine-pyrimidine dC-dC homo base pair. The dZ-dC pair forms a mismatch in the absence of silver ions and matches after addition of metal ions. Base-pair formation was verified on self-complementary 6-mer duplexes and 12-mer DNA with random composition by UV-dependent T-m measurements. Modified silver-mediated and hydrogen-bonded canonical base pairs can coexist. The dZ-Ag+-dC base pair is slightly less stable than the dG-dC pair, shows sequence dependence, and consumes one or two silver ions. These properties make the dZ-Ag+-dC pair suitable for programmable incorporation of silver ions in DNA which cannot be achieved by canonical base pairs. If the silver ion content is higher than the total number of base pairs the duplexes turn into very stable structures in which all base pairs are considered to be in the silver-mediated pairing mode.