Pairing strength and proton characters of the N7,N9-dimethylated GC and AT base pairs: a density functional theory investigation

Abstract

The pairing strength, proton properties associated with proton transfer and deprotonation as well as relevant structural perturbations of 7,9-dimethyl GC ([mGC]⁺) and 7,9-dimethyl AT ([mAT]⁺) base pairs have been investigated. Energies related to proton transfer and deprotonation have also been predicted. It is found that the guanine/adenine N7 methylation improves the stability of GC/AT base pair. The proton transfer between the guanine N1 and the cytosine N3 is observed in [mGC]⁺ with an out-of-plane transition state. However, no proton-transfer reaction occurs for [mAT]⁺. For the deprotonation of [mGC]⁺ and [mAT]⁺, guanine C8 and N1 and adenine C8 are the most favorable sites. Deprotonation from the pyrimidine N1 site generates the most stable deprotonated base pairs, and the dissociation energies surprisingly amount to ∼100.00 and ∼65.49 kcal mol⁻¹, respectively, much higher than those of their neutral base pairs. Deprotonation from the other sites of pyrimidine exhibits the most significant structural changes and gives the most interesting deprotonated base pairs. This process is accompanied by a barrier-free proton transfer (BFPT) from guanine N1 to cytosine N3 or adenine N6 to thymine N3 or O4 site. In this way, two rare imino tautomers of cytosine (trans-C* or cis-C*) are easily generated by removing a proton from the N4 site of cytosine in [mGC]⁺. In addition, the reason for BFPT from guanine N1 to cytosine N3 has been explored.