Selective Na+/K+ Effects on the formation of alpha-cyclodextrin complexes with aromatic carboxylic acids: competition for the guest

We investigated the effects of K+ and Na+ ions on the formation of a-cyclodextrin complexes with ionized aromatic carboxylic acids. Using solution calorimetry and H-1 NMR, we performed the thermodynamic and structural investigation of a-cyclodextrin complex formation with benzoic and nicotinic acids in different aqueous solutions containing K and Na+ ions as well as in pure water. The experiments show that the addition of sodium ions to solution leads to a decrease in the binding constants of the carboxylic acids with a-cyclodextrin as compared to pure water and solutions containing potassium ions. From another side, the effect of potassium ions on the binding constants is insignificant as compared to pure water solution. We suggest that the selectivity of cation pairing with carboxylates is the origin of the difference between the effects of sodium and potassium ions on complex formation. The strong counterion pairing between the sodium cation and the carboxylate group shifts the equilibrium toward dissociation of the binding complexes. In turn, the weak counterion pairing between the potassium cation and the carboxylate group has no effect on the complex formation. We complemented the experiments with molecular modeling, which shows the molecular scale details of the formation of cation pairs with the carboxylate groups of the carboxylic acids. The fully atomistic molecular simulations show that sodium ions mainly form direct contact pairs with the carboxylate group. At the same time, potassium ions practically do not form direct contact pairs with the carboxylate groups and usually stay in the second solvation shell of carboxylate groups. That confirms our hypotheses that the selective formation of ion pairs is the main cause of the difference in the observed effects of sodium and potassium salts on the guest-host complex formation of a-cyclodextrin with aromatic carboxylic acids. We propose a molecular mechanism explaining the effects of salts, based on competition between the cations and a-cyclodextrin for binding with the ionized carboxylic acids

Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide

The selectivity of encapsulation of leflunomide and teriflunomide by native α-, β- and γ-cyclodextrins was investigated through 1H NMR and molecular modeling. Thermodynamic analysis revealed the main driving forces involved in the binding. For α-cyclodextrin, the partial encapsulation was obtained while deep penetration was characterized for the other two cyclodextrins, where the remaining polar fragment of the molecule is located outside the macrocyclic cavity. The interactions via hydrogen bonding are responsible for high negative enthalpy and entropy changes accompanying the complexation of cyclodextrins with teriflunomide. These results were in agreement with the molecular modeling calculations, which provide a clearer picture of the involved interactions at the atomic level

α-Cyclodextrin/aminobenzoic acid binding in salt solutions at different pH : dependence on guest structure

Influence of Na+ and K+ cations on α-cyclodextrin guest-host complex formation with isomeric aminobenzoic acids was examined at different pH and temperature of 298.15K by 1H NMR and calorimetry methods. More pronounced influence of Na+ on inclusion complex formation of α-CD with aminobenzoic acid anions compare to the effects of Na+ on α-CD complex formation with zwitterionic aminobenzoic acid molecules was revealed. For the first time, the dependence of salt effects on the structure, ionization and the hydration state of the guest molecule was demonstrated and analysed on the basis of the obtained thermodynamic parameters of complex formation and calculated free energy of hydration of different ionized forms of aminobenzoic acids