Intrinsic charge polarization governs hydrogen-bonding strength in amide vs. imide self-association.

The weaker self-association of imide dimers relative to amide dimers is often attributed to repulsive secondary electrostatic interactions (SEI) between diagonally positioned carbonyl groups. Quantification of the SEI interactions using quantum chemical analyses reveals that they are negligible and do not explain the stronger self-association of amides. Instead, amides exhibit a larger intrinsic charge polarization, resulting in a more favorable alignment of hydrogen-bond donor and acceptor regions. This enhanced polarization strengthens the electrostatic attraction between the monomers and simultaneously reinforces the covalent component of the hydrogen bond through more favorable donor-acceptor orbital interactions. Our findings demonstrate that intrinsic charge polarization within the monomers, rather than secondary electrostatic interactions between frontier atoms, governs the stability of hydrogen-bonded amide and imide dimers, highlighting the importance of quantum-mechanical descriptions for understanding hydrogen-bond strengths.