| Dissolution is a fundamental process that is vital for chemical engineering.Unfortunately,many natural bioactive compounds?NBCs?exhibit poor solubility due to their high molecular weights and structural complexity,which leads to low bioavailability and substantially hinders the development of efficient separation medium.In this research,the dissolution characteristics of a series of typical NBCs in ionic liquids?ILs?were studied and the mutual interactions and molecular assembly mechanism between ILs and NBCs were systematically investigated.Based on these,A new IL-based solvent system,with high dissolution abilities was constructed.A family of long-chain carboxylate ILs?LCC-ILs?with strong hydrogen-bonding?H-bond?basicity and excellent lipophilicity was designed for the solubilization of sparingly soluble drug-like molecules.The nanoscale structure of LCC-ILs was demonstrated and the solubilities of seven different drug-like molecules in LCC-ILs were determined.Based on the investigated interactions and microstructures between LCC-ILs and drug-like molecules,a novel and versatile approach,referring to as a self-assembly induced?SAI?solubilization strategy was developed using a nano structured ILs.With this strategy,highly ordered liquid crystals?LCs?were formed via H-bond and van der Waals force self-assembly,resulting in extremely high solubilities of these drug-like molecules.The solubility of cholesterol in tetrabutylphosphonium palmitate?[P4444][C15H31COO]?was as high as 0.91 mol·molF-1 at 50 ?,which was 5?8000-fold higher than those of organic solvents,micelles/microemulsion and common ILs.In addition,the SAI stragety also showed the highest solubility level reported in the literature for other drug molecules,including steroids?hydrocortisone and vitamin D3?,sterols?stigmasterol?and arylpropionic acid derivatives?naproxen and indomethacin?.Seven kinds of novel ILs with branched-chian carboxylate anion?named BCC-ILs?were designed for the first time to improve the H-bond basicity and lipophilicity.And their properties,including melting point/glass transition temperature,thermal decomposition temperature,viscosity,H-bond basicity[? and dipolarity ?*were characterized.The results demonstrated that the BCC-Ls achieved a higher ? values??=1.49?1.66,30 ??,a lower ?*?0.75?0.95,30 ??,a higher viscosity?300?505 mPa·s,25 ??and a litter lower thermal stability?TD>196 ??than LCC-ILs in same conditions.The BCC-ILs exhibited a better dissolution ability for cholesterol than LCC-ILs.A family of new water/LCC-IL mixtures was constructed,attributed to the unique amphipathic property of LCC-ILs,which have excellent lipophilicity while still being water-miscible.The water/LCC-IL mixtures exhibit extremely high solubilities for various HBCs.The quantitative solubilities of tocopherol,perillyl alcohol,rutin,and ginkgolides in 70 wt%tetrabutylphosphonium palmitate laurate?[P4444][C11H23COO]?aqueous solutions were as high as 1.46,0.71,0.39 and 0.43 g·g-1 respectively,all are the highest solubilities in aqueous solutions ever reported.The microscopic solvent properties and dissolution mechanism were investigated and nano-micelles were observed by DLS when tocopherol was dissolved in water/LCC-IL mixtures.The water/LCC-IL mixtures also exhibited excellent performance in the extraction of tocopherols from biomass with a yield two to 12 times that in common solvents.Aim to combine good kinetic properties?lower viscosity?and greatly enhanced solubility,a family of new molecular solvent/LCC-IL mixtures with LCC-ILs as a key component was constructed.The effects of molecular solvent type and concentration on solubility and self-assembly behaviors were systematically investigated.A synergistic effect between the molecular solvents and LCC-ILs was revealed,which contributed to enhanced solute-solvent self-assembly in dissolution over pure LCC-ILs and thus greatly elevated solubility.The quantitative solubility of cholesterol was as high as 0.84 g·g-1 at 25? in n-heptane/[P4444][C15H31COO]?40 wt%?mixtures,which were the highest solubility of cholesterol ever reported,six-to 980-fold higher than traditional molecular solvents and even one-to seven-fold higher compared to pure LCC-ILs,while maintained a low viscosity?24.9 mPa·s,25 ??.These excellent dissolution results demonstrated the considerable potential of LCC-ILs,BCC-ILs and related mixted systems as promising solvents for the aeras including separation and purification of NBCs,drug solubilization and delivery,catalysis and synthesis processes,and so on. |
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