Does the A.T or G.C base-pair possess enhanced stability? Quantifying the effects of CH...O interactions and secondary interactions on base-pair stability using a phenomenological analysis and ab initio calculations.

An empirically based relationship between overall complex stability (-DeltaG degrees ) and various possible component interactions is developed to probe the question of whether the A.T/U and G.C base-pairs exhibit enhanced stability relative to similarly hydrogen-bonded complexes. This phenomenological approach suggests ca. 2-2.5 kcal mol-1 in additional stability for A.T owing to a group interaction containing a CH...O contact. Pairing geometry and the role of the CH...O interaction in the A.T base-pair were also probed using MP2/6-31+G(d,p) calculations and a double mutant cycle. The ab initio studies indicated that Hoogsteen geometry is preferred over Watson-Crick geometry in A.T by ca. 1 kcal mol-1. Factors that might contribute to the preference for Hoogsteen geometry are a shorter CH...O contact, a favorable alignment of dipoles, and greater distances between secondary repulsive sites. The CH...O interaction was also investigated in model complexes of adenine with ketene and isocyanic acid. The ab initio calculations support the result of the phenomenological approach that the A.T base-pair does have enhanced stability relative to hydrogen-bonded complexes with just N-H...N and N-H...O hydrogen bonds.