title: Thermodynamic parameters of molecular complexes in aqueous solution: enthalpy-entropy compensation in a series of complexes of caffeine with beta- naphthoxyacetic acid and drug-related aromatic compounds.
abstract: Stability constants and thermodynamic parameters have been evaluated for the complexation reaction in aqueous solution of caffeine with beta-naphthoxy acetic acid. The values were higher than those previously reported for the complexation of other ligands with methyl xanthines. In nearly all aromatic ligands complexing with caffeine and theophylline for which data are available, both entropy and free energy of complexation were linearly related to the enthalpy, giving an isoequilibrium relationship. Salicylamide, sodium benzoate and cis-methyl cinnamate exhibited slight deviations on the delta G-delta H plot; the non-aromatic dehydroacetic acid showed the largest deviation. The isoequilibrium relationship was shown to be valid statistically (349-365 K, caffeine systems; 353-372 K, caffeine and theophylline systems) indicating underlying chemical causation. Thermodynamic equations are presented for analysis of the factor involved, which are attributed to a combination of substrate-ligand interactions and solvent effects. The substrate-ligand overlap area is considered as a common parameter through which the solvent and interaction forces might cooperate to give rise to linearity in the isoequilibrium relationship. The increasingly negative experimental values of the enthalpy and entropy with increase in ligand planar overlap area are discussed in relation to the underlying forces involved in the complexation.
mesh_terms: D002110:Caffeine; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D006016:Glycolates; D008956:Models, Chemical; D012996:Solutions; D013696:Temperature; D013816:Thermodynamics
chemical_list: D006016:Glycolates; D012996:Solutions; D002110:Caffeine; C008586:2-naphthoxyacetic acid