Complexation of Cyclodextrins with Benzoic Acid in Water-Organic Solvents: A Solvation-Thermodynamic Approach

The aim of this research is to obtain new data about the complexation between beta-cyclodextrin (beta-CD) and benzoic acid (BA) as a model reaction of the complex formation of hydrophobic molecules with cyclodextrins (CDs) in various media. This research may help developing cyclodextrin-based pharmaceutical formulations through the choice of the appropriate solvent mixture that may be employed in the industrial application aiming to control the reactions/processes in liquid phase. In this paper, NMR results for the molecular complex formation between BA and beta-CD ([BA subset of beta-CD]) in D2O-DMSO-d(6) and in D2O-EtOH have shown that the stability of the complex in the H2O-DMSO-d(6) varies within the experimental error, while decreases in H2O-EtOH. Changes in the Gibbs energy of BA resolvation in water and water-dimethylsulfoxide mixtures have been obtained and have been used in the analysis of the reagent solvation contributions into the Gibbs energy changes of the [BA subset of beta-CD] molecular complex formation. Quantum chemical calculations of the interaction energy between beta-CD and BA as well as the structure of the [BA subset of beta-CD] complex and the energy of beta-CD and BA interaction in vacuum and in the medium of water, methanol and dimethylsulfoxide solvents are carried out. The stability of [BA subset of beta-CD] complex in H2O-EtOH and H2O-DMSO solvents, obtained by different methods, are compared. The thermodynamic parameters of the [BA subset of beta-CD] molecular complexation as well as the reagent solvation contributions in H2O-EtOH and H2O-DMSO mixtures were analyzed by the solvation-thermodynamic approach.

Automated summary

This research aims to investigate the complexation between beta-cyclodextrin and benzoic acid in various solvents, providing insights into the stability and Gibbs energy changes of the molecular complex formation. Quantum chemical calculations are utilized to analyze the interaction energy and structure of the complex, comparing the stability in different solvent mixtures. The thermodynamic parameters and solvation contributions of the molecular complexation are analyzed using a solvation-thermodynamic approach.