Effect of choline chloride based deep eutectic solvents on the aqueous solubility of 4-hydroxycoumarin drug: Measurement and correlation

This work aims to improve the aqueous solubility of 4-hydroxycoumarin (4H-coumarin) as one of the lowest soluble derivatives of coumarin, by using deep eutectic solvents (DESs). The applied DESs are composed of choline chloride (ChCl) as a hydrogen bond acceptor (HBA) and ethylene glycol (EG), urea (U), or glycerol (GLY) as hydrogen bond donors (HBD). The shake-flask method was used to determine the experimental solubility of 4H-coumarin at T = (298.15 to 313.15) K. The results demonstrate that 4H-coumarin solubility was increased noticebly at higher DES concentration and temperature. Moreover, in the presence of ChCl/EG, the 4H-coumarin solubility was more than 250 times higher than that in pure water. The experimental solubility data were fitted to the Wilson, electrolyte Non-Random Two-Liquid (e-NRTL), and UNIQUAC activity coefficient models, which shows that the Wilson model has the best correlation performance for aqueous solutions containing ChCl/EG, ChCl/GLY and ChCl/U with 0.05, 0.07 and 0.22 of ARD%, respectively. The Gibbs and van't Hoff equations to estimate the dissolution apparent thermodynamic quantities including enthalpy, Gibbs free energy, and entropy. The results indicate that 4H-coumarin dissolution processes in the investigated systems are endothermic. Quantum mechanical Density functional theory (DFT) method has also been implemented to discover the nature of the interactions in the studied DES/4H-coumarin complexes at the B3LYP-D3(BJ)/6-311g(d,p) level of theory. The DFT calculations confirm that the formations of the DESs and DES/4H-coumarin complexes are spontaneous, and the most dominant interactions are hydrogen-bonding of Cl from ChCl as electron donor and H of the other components as electron acceptor. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

This study aimed to improve the aqueous solubility of 4-hydroxycoumarin by using deep eutectic solvents (DESs). The results showed that the solubility of 4-hydroxycoumarin significantly increased with higher DES concentration and temperature. The Wilson model provided the best correlation for aqueous solutions containing different DES compositions, and the dissolution process of 4-hydroxycoumarin was found to be endothermic. Quantum mechanical Density functional theory (DFT) calculations confirmed the spontaneous formation of DESs and DES/4-hydroxycoumarin complexes through hydrogen bonding interactions.