Hydrogen Evolution Facilitates Reduction of DNA Guanine Residues at the Hanging Mercury Drop Electrode: Evidence for a Chemical Mechanism

Abstract

Guanine (G), as well as G residues in nucleosides, nucleotides and nucleic acids, undergo chemically reversible (but electrochemically irreversible) reduction/oxidation processes at the mercury‐based electrodes. It has been established that G is reduced to 7,8‐dihydroguanine at highly negative potentials. The reduction product is oxidized back to G around −0.25 V, giving rise to anodic peak G. Previous studies suggested involvement of a chemical mechanism involving electrochemically generated hydrogen radicals in the G reduction process. In this work we studied effects of cisplatin and pH on the G reduction process. We have found that catalytic hydrogen evolution accompanying electrochemical reduction of cisplatin markedly facilitates reduction of G. Minimum negative potential required for G reduction were shifted to less negative values and correlated with the onset of catalytic currents of cisplatin. Analogous shifts of the potential of G reduction were observed upon lowering pH of the background electrolyte (i.e., increasing the availability of protons to generate hydrogen radicals). Ammonium ions markedly increased efficiency of G reduction, which may be explained by generation of active hydrogen via formation and subsequent decomposition of ammonium amalgam. Our results strongly suggest that chemical mechanism(s) involving hydrogen radicals, electrochemically and/or electrocatalytically generated at the HMDE, contribute to the guanine → 7,8‐dihydroguanine conversion.

Electrochemical Reduction and Oxidation of Six Natural 2′‐Deoxynucleosides at a Pyrolytic Graphite Electrode in the Presence or Absence of Ambient Oxygen

“…To obtain peak reG ox , reduction of the N7=C8 double bond in guanine is required . The reduction process has been proposed to involve a chemical mechanism employing H radicals . Thus, we tentatively suggest a possibility that reA ox0 originate from oxidation of 7,8‐dihydro adenine formed via analogous chemical reduction.…”

“…Analogous peak provided by G residues in the DNA was shifted by 40 mV to more negative potentials . The potential of peak G red is substantially more negative than the potential region in which the guanine reduction process leading to 7,8‐dihydroG occurs (through the presumably chemical mechanism involving hydrogen evolution) . This deeper electrochemical reduction of the G (or 7,8‐dihydroG) residues within DNA has been also indirectly detected on HMDE via diminution of peak reG ox due to exposure to potentials more negative than −1.85 V .…”

“…The proposed mechanism involves protonation of guanine at C8, followed by radical formation and recombination with C8 radical of neighboring G . A different mechanism behind G reduction peak should be considered in aqueous media on HMDE or PGE during hydrogen evolution processes, where the first step can involve H radical attack leading to formation of 7,8‐dihydroG, which is subsequently reduced at more negative potentials, giving rise to the peak G red . This difference between reduction of G in aqueous and ionic liquid electrolytes is supported by the absence of peak reG ox in the latter medium .…”

“…On the other hand, even for E v =−1.40 V (far before peak G red ) a very small but detectable peak reG ox is present (Figure and S4). This supports the previously proposed hypothesis that background hydrogen evolution plays a key role in reduction of G to a product(s) which subsequently give(s) the peak(s) reG ox .…”

“…None of these peaks was observed in studies with DNAs containing the same bases. These peaks might appear due to a similar mechanism as has been proposed earlier for the peak (discussed in section 3.1.8) , but a more detailed study beyond the scope of this qualitative overview is needed to verify this suggestion. Thus, oxidation or reduction of nucleobases within DNA and oxidation or reduction of corresponding dNs may occur through different mechanisms and yield different products.…”