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

Tatyana R Usacheva,Thi Lan Pham,Marco Biondi,Valentin A Sharnin,Thi Thu Ha Nguyen,Natalya N Kuranova,Roman A Kushnir,Dzhovidon N Kabirov,Viktor T Panyushkin,Diana A Alister,George A Gamov,Vitaly A Volynkin,Dmitry A Lindt,Concetta Giancola,Thi My Hanh Le

doi:10.3390/molecules26154408

Abstract

The aim of this research is to obtain new data about the complexation between β-cyclodextrin (β-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 β-CD ([BA⊂β-CD]) in D2O-DMSO-d6 and in D2O-EtOH have shown that the stability of the complex in the H2O-DMSO-d6 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⊂β-CD] molecular complex formation. Quantum chemical calculations of the interaction energy between β-CD and BA as well as the structure of the [BA⊂β-CD] complex and the energy of β-CD and BA interaction in vacuum and in the medium of water, methanol and dimethylsulfoxide solvents are carried out. The stability of [BA⊂β-CD] complex in H2O-EtOH and H2O-DMSO solvents, obtained by different methods, are compared. The thermodynamic parameters of the [BA⊂β-CD] molecular complexation as well as the reagent solvation contributions in H2O-EtOH and H2O-DMSO mixtures were analyzed by the solvation-thermodynamic approach.

Highlights

In recent studies [2,3], we have reported on the effect of reagents solvation on amine stability, the effect of reagents solvation on changes in the stability of amine, carboxylate, and coronate complexes of d-metal ions, as well as the thermodynamic characteristics of complexation reactions in water–organic solvents
The inclusion complexes are formed mainly due to weak interactions, complexation induces relatively small chemical shifts
In β-cyclodextrin protons H4 and H2 of the glucopyranose residues are located on the outer side, and protons H3 and H5 on the inner side of the macrocyclic cavity (Figure 1)

Summary

Introduction

The analysis of molecular complexation reactions of crown ethers and cryptands with amino acids and peptides shows that the solvation contributions of the host and guest molecules play a different role on the change of the coordination compound and the energy of the reactions [8,9]. To predict the shift of equilibrium in the reactions of biologically active molecules, it is necessary to extend the knowledge of solvent influence on these processes In this context, the aim of this research is to obtain new data of the complexation between β-cyclodextrin (β-CD) and benzoic acid (BA) as a model reaction of the complex formation of hydrophobic molecules with cyclodextrins (CDs) in various media. The different influence of water and non-aqueous media on molecular complexation suggests the possibility to improve CDs ability to enhance the apparent solubility of hydrophobic molecules by changing the solvent as a medium of occurring processes

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Conclusion