Gold‐Mediated Base Pairs in Nucleic Acids: Selective Coordination to Natural and Thiocarbonyl‐Modified Cytosines Dependent upon the Oxidation State of Gold

Gold-mediated base pairing in nucleic acids has remained poorly understood, despite structural analogies with mercury and silver ions known to coordinate selectively to mismatched base pairs. Here, the crystal structures of a CAu(I)C base pair and a CGAu(I)C base triple formed with natural nucleobases are reported. Although solution-phase thermodynamic analysis of Au(I) coordination is technically unfeasible, structural evidence supports its selective insertion into the base mismatches. In contrast, duplexes incorporating 2-thiocytosine form square-planar complexes with Au(III), and melting temperature analysis shows significant thermal stabilization. The distinct coordination geometries of Au(I) and Au(III) arise from differences in oxidation state and preferred coordination numbers, with Au(I) favoring linear two-coordinate structures and Au(III) forming square-planar complexes stabilized by thiocarbonyl donors. These findings establish a structure-guided strategy for oxidation-state-selective metal coordination in nucleic acids, paving the way for the design of metal-responsive DNA architectures with tunable properties.