Solubility of collinin and isocollinin in pressurized carbon dioxide: Synthesis, solubility parameters, and equilibrium measurements

Collinin is a derivative of coumarin that has shown remarkable potential against cancer, tuberculosis, periodontitis, and other prevalent diseases, and is usually extracted from plants of the Rutaceae family at a very low yield. In this work, collinin and a position-isomer herein called isocollinin were synthesized at different scales (from 1 to 50 g of precursor) by a route consisting of two parallel and two sequential chemical reactions. The isomers were characterized by ¹H NMR, ¹³C NMR, nuclear Overhauser enhancement spectroscopy NMR, melting temperature, and melting enthalpy. For each isomer, the Hansen solubility parameters and the radius of its solubility sphere were experimentally determined by solubility tests in 15 common solvents and two solvent blends. The solubility of each isomer in pressurized CO₂ was determined at 30 and 50 °C from 72.2 to 112.9 bar, by an in situ high-pressure spectrometry technique, which was validated with the anthracene-CO₂ system. The solubility of both isomers in CO₂ increased with pressure in the range of temperatures and pressures considered, but that of collinin exhibited an asymptotic behavior around 80.8 and 104.8 bar, at 30 and 50 °C, respectively.