Thermodynamic parameters for the association of natural and substituted alpha-, beta-, and gamma-cyclodextrins with acetylsalicylic acid, salicylic acid and ibuprofen have been determined by isothermal titration calorimetry. Analysis of the data shows that complexes form, all having 1:1 stoichiometry. The shape-matching between the host and guest is the factor determining the values of the thermodynamic quantities. In the case of the smallest cyclodextrin interacting with acetylsalicylic acid and salicylic acid, the parameters indicate that hydrophobic interactions play the major role. Association occurs through the shallow inclusion of the benzene ring into the cavity. In the case of substituted beta-cyclodextrins, instead, inclusion of the benzene ring is deeper and the tight fitting of the guest molecule to the cavity makes the enthalpy and entropy to be both negative. Ibuprofen interacts through its isobutyl group: the values of the association constants are very high for beta-cyclodextrins as determined by the large and positive entropies due to the relaxation of water molecules from the cavity and the hydration spheres of the interacting substances. For all systems, a compensatory enthalpy entropy relationship exists unless for those involving beta-cyclodextrins and ibuprofen. (C) 2013 Elsevier B.V. All rights reserved.