Three novel water-soluble calix[4]arene derivatives bearing amide binding sites for metal cati-ons were prepared. Glucose units were embedded in their structures as neutral hydrophilic frag-ments which enable solubility in water. Syntheses were performed through a series of reactions starting from p-tert-butylcalix[4]arene. Glycosylation was carried out using copper catalyzed alkyne azide cycloaddition, whereas amide groups were introduced using standard techniques in calixarene chemistry. The compounds differed in the type of cation-binding site (secondary or tertiary amide) as well as position and number of glucose units. Complexation of the prepared ligands with alkali metal cations in water, methanol and formamide was studied in order to get insight into the effect of solvation as well as intra- and intermolecular hydrogen bonds on the equilibria of the corresponding reactions. Stability constants of 1:1 complexes were determined by means of UV spectrophotometric and microcalorimetric titrations. Calorimetric measure-ments provided also reaction enthalpies and entropies. It should be noted that such studies were for the first time undertaken with neutral calixarens in aqueous solutions. The complexation reaction equilibrium constants decreased in the solvent order: methanol > formamide > water, which could be accounted for by considering the differences in solvation of cations in these solvents. In most cases the stability constants of the complexes decreased in the cation order: Na+ > K+ > Li+ > Rb+, whereas no complexation was observed in the case of the largest Cs+. The highest stability constants corresponded to tertiary-amide derivative bearing eight glucose units at the lower rim, and this derivative was proven to be capable of remarkably efficient (log K ≈ 5) and pronouncedly selective binding of sodium cation in water. All the obtained results were thoroughly discussed with respect to the developed synthetic routes, as well as the influ-ence of solvation and ligands structural characteristics on the thermodynamic stability of their complexes with alkali metal cations.