Understanding the large solubility of lidocaine in 1-n-butyl-3-methylimidazolium based ionic liquids using molecular simulation.

Room temperature ionic liquids have been proposed as replacement solvents in a wide range of industrial separation processes. Here, we focus on the use of ionic liquids as solvents for the pharmaceutical compound lidocaine. We show that the solubility of lidocaine in seven common 1-n-butyl-3-methylimidazolium based ionic liquids is greatly enhanced relative to water. The predicted solubility is greatest in BMIMCH3CO2, which we find results from favorable hydrogen bonding between the lidocaine amine hydrogen and the CH3CO2 oxygen, favorable electrostatic interactions between the lidocaine amide oxygen with the BMIM aromatic ring hydrogens, while lidocaine does not interfere with the association of BMIM with CH3CO2. Additionally, by removing functional groups from the lidocaine scaffold while maintaining the important amide group, we found that as the van der Waals volume increases, solubility in BMIMCH3CO2 relative to water increases.