Phase Equilibria and Partitioning of l-Histidine and Three Pharmaceuticals to pH-Adjusted High-Pressure Liquid Phases of the Ternary System (Ethene + Water + 2-Propanol)

Abstract

Adding some salt to a homogeneous aqueous liquid solution of an organic solvent often results in a liquidÀliquid phase split. However, such a phase split can also be achieved by charging such a liquid with a gas, in particular when the temperature is close to the critical temperature of that specific gas. This phenomenon is called "salting out by a near-critical gas". It might be applied in a high-pressure extraction process, for example, to separate and recover valuable biomolecules from aqueous phases. Using a neutral gas like, for example, ethene for pressurizing additionally allows to adjust the pH of the coexisting liquid phases and to influence the partitioning of biomolecules when they change their electric net charge with the pH of the solution. The design of such separation processes requires not only reliable information on the phase forming system, that is, the ternary system (nearcritical gas þ water þ organic solvent), but also on the partitioning of typical solutes to the coexisting phases. The present publication reports data (from an experimental study with a static-analytical device) for the partitioning of four biomolecules, that is, L-histidine, Aspirin, cimetidine, and 4-dimethylaminoantipyrine (at nearly infinite dilution) to coexisting liquid phases of the highpressure three-phase liquidÀliquidÀvapor (L 1 L 2 V) equilibrium of the ternary system (ethene þ water þ 2-propanol) at (293 and 333) K and pressures from about (5.5 to 17) MPa. The coexisting liquid phases are characterized by distinctly different compositions, the aqueous phase being more hydrophilic than the alkanol-rich phase. Moreover, electrolytes were additionally added to adjust the pH conditions in the liquid phases. The pH-dependent dissociation equilibrium and the related net charge of the biomolecules primarily determine the partitioning behavior: The pH effect is stronger than the impact of varying pressure or temperature. For example, a switch from basic to acidic conditions can invert the partitioning, if that switch at the same time effects a change in the net charge of the solute, for example, from an ionic to a neutral molecule (or vice versa). The ionic solute is more hydrophilic (and thus prefers the aqueous phase), whereas the neutral or zwitterionic solute is less hydrophilic (i.e., more lipophilic) and consequently prefers the propanol-rich liquid phase.

Liquid–Liquid Equilibria of Water + 1-Butanol + Amino Acid (Glycine or dl-Alanine or l-Leucine) at 313.15 K

“…Several studies included the partition of amino acids in aqueous two-phase systems (ATPS), by using either polymer-salt, polymer-polymer, ionic liquid-salt or hydrophobic ionic liquid-water ATPS systems [4][5][6][7][8][9][10][11]. However, just a few liquid-liquid equilibrium data have been reported in the literature [12][13][14][15]. Solid-liquid equilibrium data have been also reported [16].…”