An empirically based relationship between overall complex stability (-ΔG°) 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.
ASJC Scopus subject areas
- Colloid and Surface Chemistry