Cuprous Ions Binding to Cytosine and Guanine Oligonucleotides

Using a set of spectroscopic experiments, we investigated the binding of Cu²⁺ 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.