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 (H₂O and aromatic C−I), π-hole donors (R−C(O)Me, R−NO₂ and R−C₆F₅) and for comparison R−C₆H₅ (R=any group or atom). The ‘contact groups’ are hydrogen bond donors X−H (X=N, O, S, or R₂C, or R₃C) and lone-pair containing fragments (R₃C−F, R−C≡N and R₂C=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.