LAUSR

Abstract Organic solvents are usually used to extract artemisinin from Artemisia annua L., and they can also be the solvents for the subsequent purification or derivatization to produce compounds with more efficient antimalarial effect. However, these solvents are volatile, explosive and toxic. The designable material ionic liquids (ILs) are alternative solvents to replace traditional ones. In this work, a reliable method for screening ILs with high solvation capability for artemisinin was developed. The infinite dilution activity coefficients of artemisinin in 903 ILs, composed by 43 cations and 21 anions, were calculated by COSMO-RS, and the results implied that the solubility of artemisinin in ILs mainly depends on the anions. Solubilities of artemisinin in 14 representative ILs were tested, and the results were in good accordance with those obtained in COSMO-RS calculation. The stability of artemisinin in some typical ILs was also studied, which indicated that this drug was stable in [EMIM][BF4], [EMIM][CF3Ac], [EMIM][NTF2], [BPY][NTF2], [EMIM][SCN], and [EMIM][Ac]. The excess enthalpy analysis demonstrated that artemisinin interacted with ILs mainly through hydrogen bond. Extraction of artemisinin using the optimal IL indicated that more artemisinin could be extracted from the leaves when compared with petroleum ether (254.73 mg/mol IL vs. 14.16 mg/mol solvent), further verifying accuracy of the simulation results. Therefore, structures of ILs with high solvation capacity for artemisinin can be obtained by the COSMO-RS method.