The thermodynamic parameters for the inclusion of some naturally occurring amino acids into a series of p-sulfonated calix[4]arenes, were determined via both ¹H NMR and calorimetric titrations in buffered aqueous solution at 25 °C. The calorimetric data show that inclusion is enthalpically driven in all cases, regardless of flexibility of the host and the nature of the guest. The most efficient receptor is the calix[4]arene tetrasulfonate 1, which exists in solution at pH 7 in a cone conformation, stiffened by H-bonding at the lower rim. Molecular mechanics data help in the understanding of why some hosts do not form inclusion complexes at all. The comparison of our data with literature reports shows that there are dramatic buffer-dependent changes in the binding affinities.

The inclusion of symmetrical tetramethylammonium cation (TEMA) by the water soluble calixarene hosts 1–8 was studied at neutral pH by ¹H NMR spectroscopy and compared with that of the ditopic trimethylanilinium cation (TMA). The hosts blocked in the cone conformation and bearing sulfonate groups at the upper rim (2, 3, 5, 7 and 8) bind selectively the aromatic portion of TMA, whereas compound 4 which lacks sulfonate groups interacts only with the charged head group of TMA. The conformationally mobile compound 1 and the partial cone calixarene 6 include TMA cation in an unselective fashion. TEMA is complexed by hosts 1–7, but not by the tetraether-tetrasulfonate receptor 8. The binding constants for all the systems, as determined by ¹H NMR spectroscopy, show that inclusion is favoured by the presence of the sulfonate groups and that the complexes of the conformationally mobile receptor 1 with both guests are more stable. The thermodynamic parameters of inclusion determined by direct calorimetry for 2–TEMA and 4–TEMA systems show that in both cases the inclusion process is enthalpically driven and that the greater stability constant observed for 2–TEMA with respect to that of 4–TEMA mainly results from a less unfavourable entropic contribution, suggesting that in the 2–TEMA complex the charged sulfonate groups cause a better desolvation of the host–guest system upon inclusion.