Intramolecular hydrogen bonds in a single macromolecule: Strength in high vacuum versus liquid environments

As a weak non-covalent interaction, hydrogen bond (H-bond) is highly susceptible to the environmental interference. However, the direct quantification of a single H-bond under an interference-free condition is still a challenge. Herein, the intramolecular H-bond in a model system, poly(N-isopropylacrylamide), is studied in high vacuum by single-molecule atomic force microscopy and steered molecular dynamics simulations, which allows the precise quantification of H-bond strength in an interference-free state. Control experiments show that the H-bond is significantly weakened in nonpolar solvent, even if the dielectric constant is very close to vacuum. If a polar solvent is used as the environment, the H-bond will be further weaker or even broken. These results imply that for experiments in any liquid environment, the H-bond strength (Δ G ) will be only ∼ 50% or even less of that measured in vacuum. Further analysis shows that in liquid environments, Δ G decays in a quasi-linear way with the increase of the dielectric constant ( ε ). For H-bond studies in future, the result measured in vacuum can be set as the standard value, namely, the inherent strength. This approach will provide fundamental insights into the H-bond participated nano-structures and materials in different environments.