Description of Chiral Complexes within Functional-Group Symmetry-Adapted Perturbation Theory—The Case of (S/R)-Carvone with Derivatives of (−)-Menthol

Symmetry-adapted perturbation theory (SAPT) and func-tional-group SAPT (F-SAPT) are applied to examine differences ininteraction energies of diastereoisomeric complexes of two chiral moleculesof natural origin: (S/R)-carvone with (−)-menthol. The study is extended byincluding derivatives of menthol with its hydroxy group exchanged by anotherfunctional group, thus examining the substituent effect of the interaction andthe interaction differences between diastereoisomers. The partitioning of theinteraction energy into functional-group components allows one to explainthis phenomenon by the mutual cancellation of attractive and repulsiveinteractions between functional groups. In some cases, one can identifydominant chiral interactions between groups of atoms of carvone andmenthol derivatives, while in many other instances, no major interaction canbe distinguished and the net chiral difference results from subtle nearcancellation of several smaller terms. Our results indicate that the F-SAPT method can be faithfully utilized for such analyses.