A Supramolecular System for Quantifying Aromatic Stacking Interactions

• Published in: Chemistry : a European journal 2001-11, Vol.7 (22), p.4863-4877
• Main Authors: Adams, Harry, Hunter, Christopher A., Lawson, Kevin R., Perkins, Julie, Spey, Sharon E., Urch, Christopher J., Sanderson, John M.
• Format: Article
• Language: English
• Subjects: aromatic stacking; double‐mutant cycle; hydrogen bonds; molecular recognition; pi interactions
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/1521-3765(20011119)7:22<4863::AID-CHEM4863>3.0.CO;2-3

A supramolecular complex for investigating the thermodynamic properties of intermolecular aromatic stacking interactions has been developed. The conformation of the complex is locked in a single well‐defined conformation by an array of H‐bonding interactions that force two aromatic rings on one end of the complex into a stacked geometry. Chemical double‐mutant cycles have been used to measure an anthracene–aniline interaction (+0.6±0.8 kJ mol−1) and a pentafluorophenyl–aniline interaction (−0.4±0.9 kJ mol−1) in this system. Although the interactions are very weak, the pentafluorophenyl interaction is attractive, whereas the anthracene interaction is repulsive; this is consistent with the dominance of π‐electron electrostatic interactions. The nitropyrrole subunits used to control the conformation of these complexes lead to problems of aggregation and multiple conformational equilibria. The implications for the thermodynamic analysis are examined in detail, and the double‐mutant‐cycle approach is found to be remarkably robust with respect to such effects, since systematic errors in individual experiments are removed in a pair‐wise fashion when the cycle is constructed. The supramolecular complex shown uses H‐bonds to force two aromatic groups to stack. Double‐mutant cycles were used to measure the aromatic stacking interaction energies: the anthracene–aniline interaction shown is repulsive, but the corresponding pentafluorophenyl–aniline interaction is attractive.