Molecular torsion balances: Evidence for favorable orthogonal dipolar interactions between organic fluorine and amide groups

(Figure Presented) Finding the right balance: An indole-extended molecular torsion balance has the geometry for measuring a truly orthogonal noncovalent interaction between a C-F bond dipole and an amide carbonyl group (see picture, green F, red O, blue N). Employing a double-mutant cycle approach, negative interaction free enthalpies were determined. Thus orthogonal dipolar interactions can be a new tool for stabilizing protein-ligand complexes and assembling supramolecular architectures. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.