Influence of Stacking on the Hydrogen Bond Donating Potential of Nucleic Bases.

Hydrogen bonding is the dominant interaction in the pairing of nucleic bases and largely determines the stability of the double-helical structure of DNA. In a previous study, we used the molecular electrostatic potential (MEP) near a hydrogen-bond (HB) acceptor to demonstrate that the intrastrand π-π stacking interaction influences the interstrand HB accepting capacity of DNA/RNA bases. In the present work, we first examined at the MP2/6-31G(d) level whether the MEP near a HB donating site of an aromatic or nucleic base can be used as a computationally inexpensive measure for its HB donating potential, quantified as the interaction energy with an HB acceptor probe, and whether this also holds in the presence of a stacking partner. A good correlation was found for substituted anilines in a vacuum, and this seemed to hold for cytosine, stacked with substituted benzenes. However, when stacked pairs of nucleic bases were studied, no correlation between the MEP and the HB strength was found. This turned out to be caused by the direct interaction of the HB donor's stacking partner with the probe molecule as well as its influence on the MEP. After this perturbation was eliminated, a significant correlation was found. The influence of stacking on the HB donating potential was shown to be dominated by the stacking geometry and not by the nature of the stacking partner. The present findings suggest that the π-π interaction on itself does not have an overall strengthening on H bonding in DNA.