Enhancing Artemisinin Solubility in Aqueous Solutions: Searching for Hydrotropes based on Ionic Liquids

Artemisinin is a sesquiterpenoid lactone peroxide, known for its potent antimalarial activity that can be extracted from Artemisia annua L. This compound is only sparingly soluble in water, making its extraction using environmental-friendly and non-toxic aqueous solvents difficult. In the attempt to overcome this limitation, hydrotropes, which are a class of compounds that can assist in increasing the solubility of hydrophobic solutes in water, were investigated in this work. In particular, the hydrotropic capability of ionic liquids (ILs) on the aqueous solubility of artemisinin was studied. The effects of IL concentration and anion nature of 1-butyl-3-methylimidazolium-based ILs on the solubility of artemisinin at 303.2 K in water were evaluated. It is here shown the excellent capacity of ILs containing thiocyanate or dicyanamide anions to enhance the solubility of artemisinin in aqueous media, with a magnitude comparable to that obtained with the best organic solvents. Furthermore, solvatochromic parameters of the ILs aqueous solutions were also measured and combined with COSMO-RS and the cooperative hydrotropy model to establish relations between the artemisinin solubility enhancement and the solvent characteristics. The solubility enhancement of artemisinin is favored by the apolarity of the medium and the lower hydrogen-bond acceptor character of the hydrotrope. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study investigated the potential of ionic liquids in enhancing the water solubility of artemisinin, finding that ionic liquids containing thiocyanate or dicyanamide cations can significantly increase the solubility of artemisinin in water, comparable to the best organic solvents. Through experimental and modeling analysis, it was discovered that the apolarity of the solvent and the lower hydrogen-bond acceptor character of the hydrotrope are favorable for the solubility enhancement of artemisinin.