title: Quantitative determination of intermolecular interactions with fluorinated aromatic rings.
abstract: The chemical double mutant cycle approach has been used to investigate substituent effects on intermolecular interactions between aromatic rings and pentafluorophenyl pi-systems. The complexes have been characterised using 1H and 19F NMR titrations, X-ray crystal structures of model compounds and molecular mechanics calculations. In the molecular zipper system used for these experiments, H-bonds and the geometries of the interacting surfaces favour the approach of the edge of the aromatic ring with the face of the pentafluorophenyl pi-system. The interactions are generally repulsive and this repulsion increases with more electron-withdrawing substituents up to a limit of +2.2 kJ mol(-1), when the complex distorts to minimise the unfavourable interaction. Strongly electron-donating groups cause a change in the geometry of the aromatic interaction and attractive stacking interactions are found (-1.6 kJ mol(-1) for NMe2). These results are generally consistent with an electrostatic model: the polarisation of the pentafluorophenyl ring leads to a partial positive charge located at the centre and this leads to repulsive interactions with the positive charges on the protons on the edge of the aromatic ring; when the aromatic ring has a high pi-electron density there is a large electrostatic driving force in favour of the stacked geometry which places this pi-electron density over the centre of the positive charge on the pentafluorophenyl group.
authors.affiliation: Centre for Chemical Biology, Krebs Institute for Biomolecular Science, Department of Chemistry, University of Sheffield, UK.
authors.forename: H
authors.initials: H
authors.lastname: Adams
authors.forename: J L
authors.initials: JL
authors.lastname: Blanco
authors.forename: G
authors.initials: G
authors.lastname: Chessari
authors.forename: C A
authors.initials: CA
authors.lastname: Hunter
authors.forename: C M
authors.initials: CM
authors.lastname: Low
authors.forename: J M
authors.initials: JM
authors.lastname: Sanderson
authors.forename: J G
authors.initials: JG
authors.lastname: Vinter
mesh_terms: D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D013816:Thermodynamics
chemical_list: D006841:Hydrocarbons, Aromatic; D006845:Hydrocarbons, Fluorinated; D007202:Indicators and Reagents; D007364:Intercalating Agents; D004247:DNA