CH–π Interactions Elucidated at the Single-Molecule Level
Qianyuan Ren, Wenying Hao, Lixia Wang, Ke Zhou, Lei Liu, Hai‐Chen Wu
Abstract
CH-π interactions represent a weak yet significant molecular force that is prevalent in diverse biological and chemical systems. Despite compelling evidence supporting the existence of CH-π interactions, experimentally measuring these weak interactions remains challenging due to the coexistence of numerous stronger noncovalent interactions. Here, we construct a refined system to accurately compare the strength of CH-π interactions between phenylalanine derivatives and aliphatic amino acids through molecular exchange processes inside a protein nanopore. Based on a quantitative comparison of binding strengths, we found that CH-π interactions are primarily governed by dispersive attraction, and a more acidic C-H bond results in stronger CH-π interactions, both of which are consistent with the literature. Most importantly, we resolved the long-standing debate regarding the deuterium isotope effect on CH-π interactions and confirmed that deuterium forms weaker CD-π interactions compared to protic CH-π interactions.