Are i-Motif Structures in DNA Compatible with Cytosine-Ag(I)-Cytosine Base Pairs?

To evaluate whether the protons of hemi-protonated C:CH⁺ base pairs in DNA i-motif structures can be replaced by silver ions, an i-motif/duplex junction (IDJ) known to be stable at pH 7 was investigated. Interestingly, only the most accessible out of five C:CH⁺ pairs in the structure can be converted into a C-Ag^I-C base pair, as was derived by ¹H NMR spectroscopy, luminescence spectroscopy, temperature-dependent UV spectroscopy, and isothermal titration calorimetry (ITC). When more than one silver ion is present per IDJ, dynamic light scattering (DLS) and CD spectroscopy indicate that the IDJ rearranges into a larger aggregated structure, likely to contain non-canonical silver-mediated base pairs. The study suggests that-in contrast to earlier reports-the DNA i-motif in general is not compatible with the formation of contiguous C-Ag^I-C pairs.