Dipoles affect conformational equilibrium

Electric dipoles are ubiquitous. They affect charge transfer, self-assembly, materials performance, and enzymatic activity. Herein, we demonstrate dipole effects on molecular geometry. An aromatic amide, 5-N-amide derivative of anthranilamide (Aaa), assumes two stable conformations with drastically different dipole moments. In non-polar solvents, Aaa exists predominantly as the conformer with the smaller dipole as nuclear Overhauser effect (NOE) and density-functional theory (DFT) analysis reveal. Increasing medium polarity drives the emergence of the other structure with the larger dipole. Splitting of the NMR signals at low temperature is consistent with capturing the two Aaa conformers upon its aggregation. Analysis employing density-functional theory quantifies the dynamics of the equilibrium between the two conformations and how solvent polarity affects it. This synergy between molecular electric dipoles and medium polarity reveals a paradigm for conformational switching.