The calculated base pairing energy of 8-oxoguanine in the syn-anti conformation with cytosine, thymine, adenine and guanine

8-Oxoguanine (8OG) is a mutagenic oxidative product of guanine, which may serve as a mispairing lesion during DNA duplication. It can form syn-anti conformation with cytosine (C), thymine (T), adenine (A) and a syn-anti like base pair with guanine (G). Using the density functional theory (DFT) we calculated the base pairing energies of these species. The resulting energies are all approximately −10 kcal mol−1, which is ∼15 kcal mol−1 lower than for the classical Watson-Crick G-C base pair and the competing 8OG-C classical pair. According to this, 8OG syn-anti configuration is un-favored when it comes to base pairing but not impossible, explaining the lack of specificity of 8OG. Oxidation of 8OG-C and 8OG-A leads to a proton shift from 8OG+ to C and A, i.e. charge spin separation occurs. Furthermore, the oxidation event results in ∼20 kcal mol−1 increase in the H-bond strength, which is again lost when the proton is removed from the N1-nitrogen of 8OG. All of the investigated base pairs form planar structures, in respect to the nucleotides making up the pairs, except 8OG-C that forms a ∼30° angle.