Electrochemical Characterization of Site‐Specifically Metal‐Modified DNA Films on Gold Electrode Surfaces

The electrochemical characterization of DNA films with different base mismatches or with Cu^II- or Ag^I-mediated pairs was carried out to assess possible immobilization and interaction effects. Toward this end, 3-hydroxy-2-methylpyridin-4(1H)-one (H), imidazole-4-carboxylate (K), purine-6-carboxylate (P), and 7-deaza-6-pyrazolylpurine (D) were used as artificial metal-binding nucleobases. Cyclic voltammetry and square-wave voltammetry confirmed the immobilization of suitably modified oligonucleotides on Au electrodes. The incorporation of the metal ions into the base mismatches to form metal-mediated base pairs showed a negligible effect on the peak potentials. Ambiguous electrochemical impedance spectroscopy results were obtained for DNA with metal-mediated base pairs, as some duplexes showed no effect of metal ion addition, while others showed variable charge transfer resistance (R_CT) with no discernible pattern. Notably, the formation of Ag^I-mediated base pairs induced larger relative changes in R_CT compared to Cu^II-mediated base pairs. Amongst the latter, only strands containing the artificial nucleobase H showed statistically relevant sequence- and distance-dependent charge transfer changes upon metalation. The data indicate that neither nucleobase charge nor nucleobase size directly correlates with the charge transfer resistance, but suggest that changes in DNA film stiffness and hence permeability outweigh other effects.