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

Jordan R. Quinn, Steven C. Zimmerman, Janet E. Del Bene, Isaiah Shavitt

Research output: Contribution to journalArticle


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.

Original languageEnglish (US)
Pages (from-to)934-941
Number of pages8
JournalJournal of the American Chemical Society
Issue number4
StatePublished - Jan 31 2007


ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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