Selective Na⁺/K⁺ Effects on the Formation of α-Cyclodextrin Complexes with Aromatic Carboxylic Acids: Competition for the Guest

Abstract

We investigated the effects of K(+) and Na(+) ions on the formation of α-cyclodextrin complexes with ionized aromatic carboxylic acids. Using solution calorimetry and (1)H NMR, we performed the thermodynamic and structural investigation of α-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 α-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 α-cyclodextrin with aromatic carboxylic acids. We propose a molecular mechanism explaining the effects of salts, based on competition between the cations and α-cyclodextrin for binding with the ionized carboxylic acids.

Quantifying non‐covalent binding affinity using mass spectrometry: A systematic study on complexes of cyclodextrins with alkali metal cations

“…This study will provide new insights into the relative cation affinities of cyclodextrins and their applications in molecular recognition. Additionally, the research will shed light on the potential selective effects induced by the presence of alkali cations bound to the substrate on the formation of ternary complexes with biological guests …”

“…Additionally, the research will shed light on the potential selective effects induced by the presence of alkali cations bound to the substrate on the formation of ternary complexes with biological guests. [18,19] It is emphasized that quantitative identification of noncovalent interactions between biological molecules and ligands by ESI-MS is always a challenge. [20][21][22][23] To detect binding constants directly, the ion peak intensities of both reactants and products need to be monitored.…”

Thermodynamic study on salt effects on complex formation of α-, β- and γ-cyclodextrins with p -aminobenzoic acid

“…Moreover, K + displays low binding affinity to the carboxylic group of the acids. It has been shown in the literature that attraction of K + to the carboxylic group of benzoic acid [17], α-poly-l-glutamate [18], amino and acetic acids [19] is very weak and similar to the attraction of water molecules to -COOH. Based on these facts, we suppose that the salt effects revealed in our work are due to the action of the anions.…”

Thermodynamics of cyclodextrin–star copolymer threading–dethreading process

“…Although spectroscopic methods are widely employed to investigate CD-based inclusion complexes formations [7,21], calorimetry is a powerful tool to evidence supramolecular interactions, and it was successfully employed for the equilibrium characterization of inclusion processes [22][23][24][25][26] and self-assembling [27][28][29][30]. With this in mind, the pseudopolyrotaxanes formation was studied by ITC changing the size of the cyclodextrin molecules.…”