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

authors	Sales, I; Abranches, DO; Costa, P; Sintra, TE; Ventura, SPM; Mattedi, S; Coutinho, JAP; Freire, MG; Pinho, SP
nationality	International
journal	FLUID PHASE EQUILIBRIA
author keywords	Artemisinin; hydrotropy; ionic liquids; aqueous solubility; solvatochromic parameters
keywords	POLARITY; SOLVENT
abstract	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.
publisher	ELSEVIER
issn	0378-3812
isbn	1879-0224
year published	2021
volume	534
digital object identifier (doi)	10.1016/j.fluid.2021.112961
web of science category	9
subject category	Thermodynamics; Chemistry, Physical; Engineering, Chemical
unique article identifier	WOS:000634506700005