Heat-capacity changes (deltaC(p)0) were determined for the complexation of 1-alkanecarboxylates with protonated hexakis(6-amino-6-deoxy)-alpha-cyclodextrin (per-NH3(+)-alpha-CD) and heptakis(6-amino-6-deoxy)-beta-cyclodextrin (per-NH3(+)-beta-CD). DeltaC(p)0 decreased with an increase in the binding constant (K) and plateaued at K = 4000 M(-1). The complexes of 1-pentanoate, 1-hexanoate, and 1-heptanoate with per-NH3(+)-alpha-CD are classified as the host-guest system in which the size of the guest fits the CD cavity well. In such a system, van der Waals interaction is the major force for complexation, leading to a negative deltaH0 value. Simultaneously, the water molecules around the hydrophobic alkyl chain of the guest and inside the CD cavity are released to the aqueous bulk phase, leading to a positive deltaS0 value. The negative deltaC(p)0 value in such complexation is ascribed to dehydration of the hydrophobic alkyl chain of the guest and extrusion of the water molecules inside the CD cavity. Meanwhile, the complexes that show positive deltaC(p)0 values are characterized by complexation in which the guest molecules are significantly smaller than the CD cavities. In such a case, the complexation is endothermic and driven by the entropy gain. When the guest is much smaller than the CD cavity, the main binding force should be Coulomb interaction. To form an ionic bond, dehydration of the charged groups must occur. This process is endothermic and leads to positive deltaH0 and deltaS0 values. As the top of the CD cavity is capped by a small but hydrophobic alkyl chain, the water molecules inside the CD cavity may form the iceberg structure. This process must be accompanied by a positive deltaC(p)0 value. Hence, the complexation of a small guest with the CD with a large cavity through Coulomb interactions shows positive and large deltaC(p)0 values. These conclusions were applied to the electrostatic binding of proteins with an anionic ligand.