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

[Image: see text] Symmetry-adapted perturbation theory (SAPT) and functional-group SAPT (F-SAPT) are applied to examine differences in interaction energies of diastereoisomeric complexes of two chiral molecules of natural origin: (S/R)-carvone with (−)-menthol. The study is extended by including derivatives of menthol with its hydroxy group exchanged by another functional group, thus examining the substituent effect of the interaction and the interaction differences between diastereoisomers. The partitioning of the interaction energy into functional-group components allows one to explain this phenomenon by the mutual cancellation of attractive and repulsive interactions between functional groups. In some cases, one can identify dominant chiral interactions between groups of atoms of carvone and menthol derivatives, while in many other instances, no major interaction can be distinguished and the net chiral difference results from subtle near cancellation of several smaller terms. Our results indicate that the F-SAPT method can be faithfully utilized for such analyses.