Solvent effects on hydrogen bonds in Watson–Crick, mismatched, and modified DNA base pairs

We have theoretically analyzed a complete series of Watson–Crick and mismatched DNA base pairs, both in gas phase and in solution. Solvation causes a weakening and lengthening of the hydrogen bonds between the DNA bases because of the stabilization of the lone pairs involved in these bonds. We have also shown that chlorouracil can mimic the behavior of thymine, and thus perfectly incorporate into a DNA strand, in nice agreement with recent experiments involving Escherichia coli. Moreover, through quantitative bond analyses in the framework of Kohn–Sham DFT, we have further consolidated the notion that donor–acceptor orbital interactions between lone-pairs and N–H σ* orbitals contribute in the same order of magnitude to the hydrogen-bond strength as electrostatic interactions.