Hydrogen bonding of 3-and 5-methyl-6-aminouracil with natural DNA bases

We have theoretically analyzed the hydrogen bonding of two artificial nucleobases (3- and 5-methyl-6-aminouracil) with the natural DNA bases using the generalized gradient approximation (GGA) of density functional theory at BP86/TZ2P level. The analysis of the monomers provides the possibility to distinguish the different active parts of molecules and the interactions with natural nucleobases have been determined. Another purpose of this work is to clarify the relative importance of electrostatic interaction vs. orbital interaction in the hydrogen bonds between the artificial base and the natural DNA base. At variance with widespread belief, the orbital interaction component in these hydrogen bonds is found to contribute about 40% of the attractive interactions and is thus of the same order of magnitude as the electrostatic component, which provides the remaining attraction. According to our theoretical results both candidates are potential artificial nucleobases for incorporation in DNA. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2008