Complexation of three kinds of tris(imidazolyl)-calix[6]arenes containing alternate p-substituents (Calix-tBu, R-1 = R-2 = tert-butyl; Calix-NH2, R-1 = tert-butyl, R-2 = NH2; Calix-NO2, R-1 = tert-butyl, R-2 = NO2) with Zn(ClO4)(2)(H2O)(6) in acetonitrile, methanol, and THF was investigated via isothermal titration calorimetry (ITC). For the coordination of these calixarene ligands to Zn(II) in acetonitrile, typical one-phase exothermic titration curves were obtained, indicating the formation of 1:1 ligand-Zn(II) complexes accompanied by large conformational changes of the ligands. In contrast, the complexation in methanol was endothermic and dominated by favorable entropy changes. The entropy gains were achieved by extensive desolvation from both Zn(II) and the ligands. ITC measurements suggest a 2:1 ligand-Zn(II) complex formation in THF in the presence of excess ligands (Calix-NH2 and Calix-NO2). The 2:1 complexes were converted to 1:1 complexes upon further addition of Zn(ClO4)(2)(H2O)(6). The results indicate the important role of a coordinating solvent (acetonitrile) for direct formation of the 1:1 complexes under the conditions of excess ligand. Complexation of a ditopic ligand (Calix-Tri) with three triazole moieties on the wider rim was also studied via ITC. The first coordination of the imidazole moieties to Zn(II) was an exothermic process. This was followed by the entropically favorable coordination of the triazole moieties to the divalent cation. We have also investigated exchange of the fourth ligand (H2O) of the Zn(II) complex of Calix-NH2 with butylamine, heptylamine, aceronitrile, and acetamide in a noncompetitive solvent, THF. The Delta H-0 tended to decrease upon increasing the ability of the guest ligand, whereas it was also affected by an entropic term due to restricted rotation of the guest ligand inside the calixarene cavity.