Influence of π-stacking on the N7 and O6 proton affinity of guanine

The influence of pi-stacking interactions between guanine (G) and the side chain of tyrosine (Tyr) on the N7 and O6 proton affinities of guanine and on the capability of these sites to act as hydrogen bond acceptors is analyzed at the B3LYP-D, M05-2X and MP2 levels of theory. With all methods, results from full geometry optimizations indicate that stacking interactions increase the N7 and O6 proton affinities by about 5-6 kcal mol(-1), the increase being slightly larger for N7. Consistently with these results, hydrogen bond distances between guanine and one water molecule decrease in the stacked system. Moreover, interaction energy between H2O and (G-Tyr) is found to be 2-3 kcal mol(-1) larger than in G center dot center dot center dot H2O. This strengthening arises from the additional Tyr-H2O stabilizing interactions and from a cooperative interplay between stacking and hydrogen bond forces.