The role of the host–guest interactions in the relative stability of compressed encapsulated homodimers and heterodimers of amides and carboxylic acids

A theoretical study has been carried out on the encapsulation of heterodimers and homodimers of p-methylbenzoic acid, p-ethylbenzoic acid, p-methylbenzamide, and p-ethylbenzamide molecules in reversible capsules with a very limited cavity. The drastic compression of the guests in the capsules has been studied by density functionally theory employing the M06-2X and ωB97X-D functionals with the 6-31G(d,p) basis set following preliminary calculations by the fast ONIOM[M06-2X/6-31G(d,p):PM6] methodology. Both functionals are in agreement with respect to the geometry, the interaction energies between the monomers and the relative ordering of the isomers. We found that encapsulation is favorable even for the larger p-ethyl compounds, but complexes of encapsulated dimers lie more than 4 kcal/mol above complexes with two non-interacting encapsulated monomers. The monomers prefer to be by themselves in the host. This is the reason why the present encapsulated dimers have not been found experimentally. The relative stability of the encapsulated complexes is reversed compared to complexes in a large cavity (Tzeli et al. in J Am Chem Soc 133:16977, 2012). This shows the possibility of separation of competitive guests via reversible encapsulation under appropriate conditions.