Reverse Watson−Crick Isocytosine−Cytosine and Guanine−Cytosine Base Pairs Stabilized by the Formation of the Minor Tautomers of Bases. An ab Initio Study in the Gas Phase and in a Water Cluster

The inclusion of the GC base pair into parallel stranded (ps) DNA requires a counterrotation of the two bases by 180° with respect to the standard Watson−Crick (WC) arrangement. This brings the two amino groups into close contact and leads also to a repulsive interaction between the two carbonyl groups. The repulsion can be eliminated by a transition to a base pair with two hydrogen bonds; however, such a structure significantly violates the backbone geometry of the ps DNA. The repulsion can also be partly relieved by involving amino group pyramidalization without major changes to the intermolecular geometry. In the present study we investigated another way to stabilize the GC base pair within ps DNA. Ab initio quantum chemical studies were performed for all three possible triply bonded hydrogen bonded reverse Watson−Crick isocytosine−cytosine (RWC iCC) base pairs with one or two minor tautomers of bases. The iCC base pair is a realistic model of the GC base pair since it has the same base pairing. The solvent effects were estimated using explicit inclusion of the first solvation shell of the base pair. Full geometry optimizations were carried out without any constraints at the HF/6-31G* level followed by single-point calculations at the correlated MP2/6-31G* level. The interaction and hydration energies were corrected for the basis set superposition error. The three base pairs investigated are higher on the potential energy surface both in the gas phase and in a water cluster as compared to the standard (antiparallel) WC base pair. However, for one structure the difference is only 9 kcal/mol in the gas phase, i.e., it is more stable than the previously postulated model with the amino−amino donor−acceptor interaction. Inclusion of hydration destabilizes the pair with respect to the standard WC pair by an additional 6 kcal/mol. The remaining two rare-tautomer RWC pairs are around 20 kcal/mol less stable than the WC base pair.