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

8-Oxoguanine (80G) 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 80G. Oxidation of 8OG-C and 8OG-A leads to a proton shift from 80G(center dot+) to C and A, i.e. charge spin separation occurs. Furthermore, the oxidation event results in similar to 20 kcal mol(-1) increase in the H-bond strength, which is again lost when the proton is removed from the N1-nitrogen of 80G. All of the investigated base pairs form planar structures, in respect to the nucleotides making up the pairs, except 8OG-C that forms alpha similar to 30 degrees angle. (c) 2004 Elsevier B.V. All rights reserved.