Molecular Torsion Balances: Evidence for Favorable Orthogonal Dipolar Interactions Between Organic Fluorine and Amide Groups

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.