DFT studies on the pairing abilities of the one-electron reduced or oxidized adenine–thymine base pair

Abstract

Using density functional theory (DFT), the hydrogen bonds making up the adenine–thymine (A–T) base pair are found to increase in total energy upon one-electron oxidation or reduction by 10.9 and 13.3 kcal mol⁻¹, respectively. Due to unsymmetric changes in the H-bond lengths, this strengthening affects an expansion of the base pair length (N1′–N9) by ∼0.27 Å. In the oxidized pair, A˙⁺–T, deprotonation from N⁶, and with the reduced pair, A˙⁻–T, protonation on N3 or N7 lead to base pairs which have similar base pairing energies as their parent A–T, i.e., the stabilization by the change in oxidation state is annihilated by (de)protonation. The calculated proton affinities of A˙⁻–T are large enough to explain its protonation by H₂O, which involves heterolytic bond cleavage of a water molecule. The N1 protonated electron adduct of A is a powerful H-bond donor; it is able to mismatch with cytosine (−28.9 kcal mol⁻¹). In DNA this could compete with the “legitimate” guanine-cytosine pairing. The pairing abilities of 2-aminopurine, an “unnatural” isomer of A, used as a fluorescent probe in DNA assemblies, are calculated to resemble those of A closely.