Macrocyclic β-cyclodextrin derivative-based aqueous-two phase systems: Phase behaviors and applications in enantioseparation

Abstract

In this work, three macrocyclic β-cyclodextrin (β-CD) derivatives, namely carboxymethyl-β-cyclodextrin (CM-β-CD), sulfobutyl ether-β-cyclodextrin (SBE-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD), were employed in the formation of novel aqueous two-phase system (ATPS) with several hydrophilic solvents respectively. It was observed that anionic β-CD derivatives (CM-β-CD and SBE-β-CD) facilitated the ATPS formation and the obtained binodal curves showed a decreasing order in inducing ATPS as acetonitrile≈1-propanol>2-propanol>ethanol. Furthermore, the proposed ATPS as a novel enantioselective liquid–liquid extraction technique was evaluated by enantioseparating racemic zopiclone (ZPC). Opposite partitioning orientations for ZPC in two groups of the investigated ATPS were studied systematically and 1-propanol/CM-β-CD ATPS was selected as the optimal enantioseparation system. Under the optimal conditions, moderate enantioseparation efficiency (α=2.58 and e.e.%=32.66%) and high recovery (RT(S)=95.54% and RT(R)=98.22%) were achieved simultaneously via a single run of extraction.