Design and analysis of interactions in ionic liquids based on procaine and pharmaceutically active anions

The present work focuses on modifying a local anaesthetic drug procaine into an ionic liquid and evaluating the resulting thermal behaviour and structural changes. Counter ions, salicylate, ibuprofenate, and docusate, were chosen due to different hydrogen-bonding abilities, molecular size, charge distribution, and functional groups. After synthesis of procaine salicylate, procaine ibuprofenate, and procaine docusate, spectroscopic investigations were performed using infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy to confirm proton transfer. Differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis were used to determine the obtained ionic liquids' thermal behaviour. Experimental measurements of density, viscosity, and electrical conductivity were performed to get insight into the interactions occurring in the obtained ionic liquids. The viscosity and electrical conductivity data were analysed using the Vogel-Fulcher-Tammann (VFT) equation, while thermal expansion coefficients were calculated from measured density data. The obtained results found that the synthesised procaine salicylate and procaine docusate an ionic liquid's behaviours, including weak intermolecular forces, while procaine ibuprofenate showed more liquid co-crystal behaviour due to the absence of proton transfer for ibuprofen. In a theoretical phase of the investigation, the density functional theory (DFT) and molecular dynamics (MD) calculations were conducted. The obtained descriptors and radial distribution functions were used to analyse the interactions between ions of synthesised ionic liquids. In addition, solubility determination results proved that procaine transformation into procaine salicylate and procaine ibuprofenate ionic liquids enhanced its solubility in water, while procaine docusate reduces procaine solubility.