Using density functional theory to design DNA base analogues with low oxidation potentials
The oxidizability of substituted nucleobases was evaluated through theoretical calculations and the ability of individual bases to induce current enhancement in the cyclic voltammograms of metal complexes. Formation of the guanine derivatives 7-deazaguanine and 8-oxoguanine is known to lower the energy for oxidation of guanine. The similar derivatives of adenine were examined and gave lower predicted redox energies as well as current enhancement with Ru(bpy)32+ (7-deazaadenine) and Fe(bpy)32+ (8-oxoadenine). Oxidizable, substituted pyrimidines were identified using a computational library that gave 5-aminocytosine and 5-aminouracil as promising electron donors. Again, these predictions were verified using catalytic electrochemistry. In addition, the computations predicted that 6-aminocytosine would be redox-active but not as easily oxidized as 5-aminocytosine, which was also confirmed experimentally. In addition to calculating the relative one-electron redox potentials, we used calculations to evaluate the loss of a proton that occurs from the initially formed radical cation. These calculations gave results consistent with the experiments, and in the case of 8-oxoadenine, the relative redox reactivity could be predicted only when the proton loss step was considered. These substituted bases constitute building blocks for highly redox-active nucleic acids, and the associated theoretical model provides powerful predictability for designing new redox-active nucleobases.
Baik, MH; Silverman, JS; Yang, IV; Ropp, PA; Szalai, VA; Yang, W; Thorp, HH
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