<p>The interaction of metal ions with nucleic acids was studied by determining the initial binding sites of Ag⁺ ions at unmodified B-DNA by NMR spectroscopy. In particular, NMR spectra were recorded of the Dickerson-Drew dodecamer sequence in the presence of different ratios of Ag⁺ ions to DNA. The data indicate that the coordination of the first three Ag⁺ ions per duplex preferentially takes place inside the B-DNA helix rather than at other possible binding sites such as the negatively charged phosphate backbone and/or the endocyclic N7 position of purine residues. Larger DNA aggregates are formed in the presence of excess Ag⁺ ions, as indicated by the formation of a precipitate and by significant changes in the circular dichroism spectra. As shown by a titration with chloride ions, the Ag⁺ ions are only loosely bound to the&#xa0;nucleic acids and can be released by precipitation of AgCl.</p> Graphical Abstract <p></p>