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

Abstract

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.

Figure 1

Optimized structures of the complexes under study.

Figure 2

Partition of the considered monomers used in the F-SAPT analysis.

Figure 3

Interaction graphs for the complexes under study. Carvone and the derivative of menthol (depicted as black vertical lines) each are divided into four fragments, as described in the main text, and are abbreviated as RC (ring), CO (carboxylic group), LC (long side-group), and MeC (methyl) for carvone and RM (ring), SubM (OH or substituent), LM (long side-group), and MeM (methyl) for menthol or the derivative of menthol. The red and blue lines depict attractive and repulsive contributions from the F-SAPT study, respectively, while the line thickness is proportional to the absolute value of the interaction energy. The rightmost figure shows differences in F-SAPT energies between the R and S diastereoisomers.