Substituent Effects on Hydrogen Bonds in DNA: A Kohn-Sham DFT Approach

In this Chapter, we discuss how the hydrogen bonds in Watson-Crick base pairs can be tuned both structurally and in terms of bond strength by exposing the DNA bases to different kinds of substitutions: (1) substitution in the X-H Y hydrogen bonding moiety, (2) remote substitution, i.e., introducing substituents in the DNA base at positions not directly involved in hydrogen bonding; and (3) environment effects which can be conceived as supramolecular substitution. The hydrogen bonds in DNA Watson-Crick base pairs have long been considered predominantly electrostatic phenomena. Here, we show with state-of the art calculations that this is not true and that electrostatic interactions and covalent (i.e. orbital interaction) contributions in these hydrogen bonds are in fact of the same order of magnitude. We also discuss the role of electrostatic and orbital interactions in the mechanism behind the substituent effects on hydrogen bonds in DNA.