Quantitative measurements of edge-to-face aromatic interactions by using chemical double-mutant cycles

Synthetic H-bonded zipper complexes have been used to quantify the magnitude of an edge-to-face aromatic interaction between a benzoyl group and an aniline ring. Four chemical double-mutant cycles were constructed by using a matrix of nine closely related complexes in which the aromatic rings were sequentially substituted for alkyl substituents. The stability constants and three-dimensional structures of the complexes were determined by using H-1 NMR titrations in deuterochloroform at room temperature. The value of the interaction energy is similar in all cases. The average is - 1.4 +/- 0.5 kJ mol(-1). The scope and limitations of the doublemutant approach are explored, and the consequences of conformational equilibria are discussed.