A hexaamine cage was synthesised in good yield by a [2+3] Schiff-base condensation followed by sodium borohydride reduction to be used as a receptor for the selective binding of anionic species. The protonation constants of the receptor, as well as its association constants with Cl−, I−, NO3−, AcO−, ClO4−, H2PO4−, SO42−, SeO42− and S2O32− were determined by potentiometry at 298.2 ± 0.1 K in H2O–MeOH (50 : 50 v/v) and at ionic strength 0.10 ± 0.01 mol dm−3 in KTsO. These studies revealed a remarkable selectivity for dianionic tetrahedral anions by the protonated receptor, with association constants ranging 5.03–5.30 log units for the dianionic species and 1.49–2.97 log units for monoanionic ones. Single crystal X-ray determination of [(H6xyl)(SO4)(H2O)6](SO4)2·9.5H2O showed that one sulfate anion is encapsulated into the receptor cage sited between the two 2,4,6-triethylbenzene caps establishing three N–H⋯O hydrogen bonds with two adjacent N–H binding sites and additional O–H⋯O hydrogen bonding interactions with six water of crystallization molecules. Four water molecules of the (SO4)(H2O)6cluster interact with [H6xyl]6+ through N–H⋯O hydrogen bonds. Molecular dynamics simulations (MD) carried out with SO42− and Cl− anions in H2O–MeOH (50 : 50 v/v) allowed the full understanding of anion molecular recognition, the selectivity of the protonated receptor for SO42− and the role played by the methanol and water solvent molecules.
