Synthesis, characterisation and antioxidant properties of ferulate-based protic ionic liquids: Experimental and modelling approaches

Active pharmaceutical ingredients (APIs) in the form of crystalline solid are commonly produced in drug manufacturing industries. However, crystalline solid APIs have a low solubility and the ability to cause polymorphism transformation. In order to overcome these problems, a modification of APIs in the form of protic ionic liquids (PILs) has been proposed. In the present study, a series of five ferulate-based PILs were successfully synthesised and characterised by appropriate spectral analysis. The antioxidant activity of synthesised PILs was determined through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays. The spectroscopy analysis confirmed the formation of PILs supported by the Density Function Theory (DFT) calculation. The synthesised ferulate-based PILs exhibited low EC50 ranging from 12.93 +/- 0.05 to 17.40 +/- 0.04 mu M indicating a strong antioxidant activity compared to parent acid (EC50 of 21.40 +/- 0.05 mu M). Prediction of antioxidant activity of the PILs and their ionic interactions at the molecular level were studied by applying DFT calculation at B3-LYP/6-311G*** level and COSMO-RS. Based on the optimised geometry, the ion-pair of PILs formed a strong directional intermolecular hydrogen bond between the -NH group of the cation with the -COOH group of the anion with interaction energy of -111 to -120 kcal mol(-1). Predicted antioxidant activity indicated that the PILs's cation has a weak interaction with an anion as observed from the sigma-potential analysis. (C) 2019 Elsevier B.V. All rights reserved.