Application of London Dispersion Corrected Density Functional Theory for Non-Covalent Ion-π Interactions

The strongly attractive non-covalent interactions of charged atoms or molecules with pi-systems are important bonding motifs in many chemical and biological systems. These so-called ion-pi interactions play a major role in enzymes, molecular recognition, and for the structure of proteins. To model ion-pi interactions with DFT, it is crucialto include London dispersion interactions, whose importance for ion-pi interactions is often underestimated. In this work, several dispersion-corrected DFT methods are evaluated for inter- and intramolecular anionic- and anion-pi interactions in larger and practically relevant molecules. We compare the DFT results with MP2, while highlyaccurate (local) coupled cluster values are provided as reference. The latter can also be a great help in the development and validation of approximate methods. We demonstrate that dispersion-uncorrected DFT underestimates ion-pi interactions significantly, even though electrostatic interactions dominate the overall binding. Accordingly, thenew charge dependent D4 dispersion model is found to be consistently better than the standard D3 correction. Dispersion-corrected DFT clearly outperforms MP2/CBS whereby the best performers come close to the accuracy limit of the reference values at considerably smaller computational cost. Due to its low cost, D4 can be combinedvery well with semi-empirical QM and force field methods, which is important in the development of more accurate methods for modeling large (bio)chemical systems (e.g. proteins). Another important aspect in modeling these charged systems with DFT is the self-interaction error (SIE). However, we do not find it to constitute a significant problem. Overall, the double hybrid PWPB95-D4/QZ turned out to be the most reliable among all assessed methods in predicting ion-pi interactions, which opens up new perspectives for systems where coupled cluster calculations are no longer computationally feasible.