New Insights into the Ion-Specific Behaviors and Design Strategies for Ion-π Interactions

Ion-pi interactions play a critical role in many important biological processes, such as gene expression, nicotine addiction, ion channel function, and so on, through recognizing specific ions by the receptors. However, widely used models, such as electrostatic potential and quadrupole moment, either treat ions as point charges or consider arenes only such that the key role of the information carried by ions is rarely discussed. Here, we shed light on the ion specificities in ion-pi interactions by correlating binding energies to a new model, namely the orbital electrostatic energy (OEE), which describes the electrostatic properties of both ions and the pi systems in detail via electron density distributions on orbitals. With this more detailed descriptor of electrostatics, new insights behind several important experimental and theoretical behaviors of ion-pi interactions are revealed, which will provide a deeper understanding of molecular recognition and communication through ion-p interactions. On top of the OEE model, an ion-specific design strategy is proposed.