Cuprous Ions Binding to Cytosine and Guanine Oligonucleotides

Using a set of spectroscopic experiments, we investigated the binding of Cu ²⁺ and Cu ⁺ to a comprehensive series of nucleic acid‐related molecules, ranging from individual nucleobases to oligonucleotides up to six nucleotides in length. We demonstrate the selective binding of Cu ⁺ to cytosine‐ and guanine‐containing oligonucleotides, as evidenced by their ability to compete with ferrozine for Cu ⁺ . The capacity to inhibit ascorbate oxidation, through effective sequestration catalytically active copper, increases with the number of cytosine residues in the oligonucleotides and is associated with the formation of a 1:1 Cu ⁺ ‐oligonucleotide complex accompanied by a pronounced conformational change. In contrast, guanine‐rich oligonucleotides exhibit the opposite behavior: they form Cu ⁺ G‐quadruplex structures that permit copper redox cycling. These findings highlight an unexpected binding of copper ions to nucleic acids in inert or redox‐active modes and thus expand its potential roles within cells through its direct interaction with DNA or RNA.