DFT and IsoStar Analyses to Assess the Utility of σ- and π-Hole Interactions for Crystal Engineering

The interpretation of 36 charge neutral 'contact pairs' from the IsoStar database was supported by DFT calculations of model molecules 1-12, and bimolecular adducts thereof. The 'central groups' are σ-hole donors (H₂ O and aromatic C-I), π-hole donors (R-C(O)Me, R-NO₂ and R-C₆ F₅ ) and for comparison R-C₆ H₅ (R=any group or atom). The 'contact groups' are hydrogen bond donors X-H (X=N, O, S, or R₂ C, or R₃ C) and lone-pair containing fragments (R₃ C-F, R-C≡N and R₂ C=O). Nearly all the IsoStar distributions follow expectations based on the electrostatic potential of the 'central-' and 'contact group'. Interaction energies (ΔE^BSSE ) are dominated by electrostatics (particularly between two polarized molecules) or dispersion (especially in case of large contact area). Orbital interactions never dominate, but could be significant (∼30 %) and of the n/π→σ*/π* kind. The largest degree of directionality in the IsoStar plots was typically observed for adducts more stable than ΔE^BSSE ≈-4 kcal⋅mol^-1 , which can be seen as a benchmark-value for the utility of an interaction in crystal engineering. This benchmark could be met with all the σ- and π-hole donors studied.