Natural Eutectic Solvent Mixture of l-Menthol/Malonic acid (4 : 1) and Its Ibuprofen Solution: Thermal and Physical Characterizations and NMR Studies of Molecular Interaction

A eutectic mixture of L-menthol and malonic acid, Me / MA (4 : 1), was characterized by calorimetry and other physical measurements. The new deep eutectic solvent (m.p. 6 °C) solvates 338 mg of ibuprofen per mL, and the solution is stable in a wide temperature range. Strategies of NMR titration used in supramolecular chemistry were employed to explore binding forces between the eutectic constituents as well as solute-solvent interaction in ibuprofen solution. Even in acetonitrile, Me ₄ MA is formed through a hydrogen-bonding network, where the constituents act as hydrogen donors and acceptors at the same time. The estimated association constant is around 30 M⁻¹; the binding forces are enough to build the eutectic mixture at high concentrations. The aggregate Me ₄ MA forms a molecular complex with ibuprofen in acetonitrile as a result of the cooperative effect of the constituents. In addition, van der Waals interactions are operative between ibuprofen and menthol in the saturated IB - Me / MA (4 : 1) solution.