Enantioseparation of Phenylsuccinic Acid Enantiomers by Solvent Sublation with Collaborative Selectors

Article abstract of DOI:10.1007/s10953-017-0689-5

A new solvent sublation (SS) system for chiral separation is introduced by using phenylsuccinic acid (H₂A) as the model enantiomers. The experiments were carried out in a traditional SS apparatus but with collaborative chiral selectors: dibenzoyl-L-tartaric acid (L-DBTA) in the organic phase and hydroxypropyl-β-cyclodextrin (HP-β-CD) in the aqueous phase. The chiral recognition abilities of the two selectors are opposite for the H₂A enantiomers. Several important parameters were investigated. The results demonstrate that enantioselective sublation and partitioning behavior are mainly dependent on the pH of the solution, the concentrations of chiral selectors and H₂A. Furthermore, the flow rate of air and flotation time also have some effects on the enantioseparation. Under the optimized conditions, the enantioselectivity expressed by the separation factor (β) and enantiomer excess (e.e.%) are 2.47 and 29.50%, and the yields of R-H₂A and S-H₂A are 0.23 and 0.13?g·L^?1, respectively. Compared with the SS system with the single selector HP-β-CD in the aqueous phase (or L-DBTA in the organic phase), the increased values of β and e.e.% in the new SS system with collaborative selectors are 1.31 (or 1.38) and 5.90% (or 13.82%), respectively.

Full text of DOI:10.1007/s10953-017-0689-5

J Solution Chem (2017) 46:2159–2170
https://doi.org/10.1007/s10953-017-0689-5
Enantioseparation of Phenylsuccinic Acid Enantiomers
by Solvent Sublation with Collaborative Selectors
Huiwen Meng1 Tao Yan1 Feipeng Jiao1 Shuai Wang1
•
•
•
Received: 24 November 2016 / Accepted: 26 July 2017 / Published online: 15 November 2017
Ó Springer Science+Business Media, LLC, part of Springer Nature 2017
Abstract A new solvent sublation (SS) system for chiral separation is introduced by using
phenylsuccinic acid (H2A) as the model enantiomers. The experiments were carried out in
a traditional SS apparatus but with collaborative chiral selectors: dibenzoyl-L-tartaric acid
(L-DBTA) in the organic phase and hydroxypropyl-b-cyclodextrin (HP-b-CD) in the
aqueous phase. The chiral recognition abilities of the two selectors are opposite for the
H2A enantiomers. Several important parameters were investigated. The results demonstrate
that enantioselective sublation and partitioning behavior are mainly dependent on the pH of
the solution, the concentrations of chiral selectors and H2A. Furthermore, the flow rate of
air and flotation time also have some effects on the enantioseparation. Under the optimized
conditions, the enantioselectivity expressed by the separation factor (b) and enantiomer
excess (e.e.%) are 2.47 and 29.50%, and the yields of R-H2A and S-H2A are 0.23 and
0.13 gÁL-1, respectively. Compared with the SS system with the single selector HP-b-CD
in the aqueous phase (or L-DBTA in the organic phase), the increased values of b and
e.e.% in the new SS system with collaborative selectors are 1.31 (or 1.38) and 5.90% (or
13.82%), respectively.
Keywords Solvent sublation Á Enantiomers Á Phenylsuccinic acid Á Preferential
recognition Á Enantioseparation
&
&
1
Feipeng Jiao
Jiaofp@163.com
Shuai Wang
wangshuai@csu.edu.cn
School of Chemistry and Chemical Engineering, Central South University, Changsha 410083,
China
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1 Introduction
Chirality has become a very important topic in the pharmaceutical industry, agrochemicals,
and food industry since a thorough assessment of potential chiral drug candidates is
required by the Food and Drug Administration (FDA) [1–3]. To date, many researchers
have attempted to obtain enantiopure compounds. The current separation techniques such
as crystallization, chromatography, kinetic resolution, chiral extraction, or membrane
separation are not always applicable for racemic compounds [4–7]. Selective extraction by
a solvent extraction system is a powerful technique for the separation and purification of
biomolecules and pharmaceutical products [8–10]. The available works most often deal
with the enantioselective extraction in O/W two-phase systems [8, 11], which are not
suitable for continuous processes and the enantioselectivity is always low. Therefore, it is
necessary to find and develop new technologies for chiral separation.
SS, which was originally introduced by Sebba, has been developed in recent years
[12–17]. SS increases in importance because this system presents many advantages,
including, high biocompatibility, a mild operation environment, easy amplification, and
low amounts of organic solvent [18, 19]. Furthermore, solvent sublation (SS) processes are
always simple to generalize to multi-stage operations, which will enable the possible full
separation of target compounds in a continuous fashion. To date, a large number of studies
related to SS have been conducted on the separation and purification of metal ions and
biological materials [20–23]. However, the applications of SS systems for chiral separation
are very limited, and no report for enantioseparation by the SS method with collaborative
selectors has been mentioned.
It is considered that the induction of chirality and the resolution of racemic compounds
necessitates the presence of a chiral environment. For this purpose, chiral auxiliaries or
selectors are needed [1]. The commonly used chiral selectors include b-CD, crown ethers,
and tartaric acid derivatives [7, 24]. Due to their low cost and excellent enantioseparation,
the applications of tartaric acid derivatives and cyclodextrin derivatives for resolution in
SS system are preferred. Cyclodextrin derivatives, which are types of cyclic oligosac-
charides, are optically active materials. They interact with guest molecules selectively, and
form inclusion complexes on the basis of the size, shape and polarity of the guest mole-
cules and various interactions. They can greatly improve the solubility of hydrophobic
enantiomers in the aqueous phase. In most cases, to further improve the solubility of
hydrophobic enantiomers and the enantioseparation efficiency, more hydrophilic b-CD
derivatives such as methyl-b-cyclodextrin and hydroxypropyl-b-cyclodextrin (HP-b-CD)
are used [11, 25]. In our study, HP-b-CD was chosen as the hydrophilic selector because of
its higher enantioselectivity. Besides, tartaric acid derivatives are normal hydrophobic
chiral selectors for many enantiomers; according to a recent report [26], dibenzoyl-L-
Fig. 1 The chemical structure of
phenylsuccinic acid
O
OH
OH
O
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tartaric acid (L-DBTA) was employed as the chiral selector in the organic solvent. H2A
(Fig. 1) is an important intermediate of N-methyl-a-phensuximide representing an
important class of antitumor agents, and thus it was used as the model enantiomers.
In this study, with the aid of collaborative selectors, a new SS system was introduced
and tried for enantioseparation using phenylsuccinic acid (H2A) as the model enantiomers.
Various process parameters, including the concentration of H2A and chiral selectors, pH,
air flow rate, and sublation time were investigated and optimized. Compared to the SS
systems with single selectors, the new SS system with collaborative selectors should
provide a more efficient approach to chiral separation.
2 Experimental Section
2.1 Materials
H2A (racemate, purity 99%) was purchased from Dibo Chemical Co. Ltd. (Shanghai
China). The aqueous chiral selector HP-b-CD was purchased from Yuanye Biotech Co.
(Shanghai China) and the organic chiral selector L-DBTA with a purity of 99% was from
Sanen Chemical Technology Co. Ltd. (Shanghai China). n-Octanol (analytically pure) was
purchased from Hengxing Chemical Material Co. (Tianjin, China). The solvent for chro-
matography was of HPLC grade. All other chemicals were of analytical reagent grade.
Double distilled and deionized water was used throughout the experiments.
2.2 Preparation of the SS System
All experiments were performed at room temperature. For each sublation experiment, The
SS system included two phases. A 100 mL H2A aqueous solution with a given concen-
tration of HP-b-CD was used as the lower phase, while 10 mL n-octanol with a given
concentration of L-DBTA formed the upper phase. The pH of the H2A aqueous solution
was adjusted with a K2HPO4–KH2PO4 buffer solution and measured using a pH meter.
The experiments for enantioseparation by the new SS system were carried out in a
traditional SS apparatus that was designed in our laboratory (Fig. 2, assembled by Hunan
University Instrument Plant, China). The whole apparatus consists of two basic parts: a
glass column (45 cm 9 25 mm i.d.) with a porous sintered glass disc at the bottom, that is
used to store the prepared phases and used as the container for enantioseparation. The other
part is an air pump with a rotameter to control the gas flow velocity, which is connected to
the column through a silicone rubber tube and used to send air to the column. When the air
passes through the porous sintered glass disc, a lot of bubbles are generated and then rise
up to the upper organic phase. Meanwhile, H2A enantiomers and the complexes formed by
H2A and HP-b-CD also rise up with the bubbles to the upper phase. The complexes don’t
dissolve in the organic phase and will come back to the lower aqueous phase after the
bubbles burst at the interface of the two phases. HP-b-CD preferentially recognizes R-H2A
rather than S-H2A, while L-DBTA has the opposite recognition tendency. Finally, more R-
H2A occurs in the lower aqueous phase compared to S-H2A, and thus the enantioseparation
purpose is achieved. It should be noted that the equipment used in SS is very simple, and
all the operator needs to do is to collect the lower aqueous layer for the sequential analysis
or further treatment.
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Fig. 2 Schematic showing the apparatus used in this work. 1—Air pump, 2—rotameter, 3—sample pool,
4—porous sintered glass disc (G4 porosity), 5—sampling vent
2.3 HPLC Analysis
After each sublation process, the concentration of H2A enantiomers in the aqueous phase
was analyzed by HPLC (Shimadzu, Japan) using
a Kromail C18-WP column
(250 mm 9 4.6 mm i.d.) (Hanbon Sci. Technol. Co. Ltd., China) and a UV spectropho-
tometer detector (Shimadzu, Japan). The quantification of H2A enantiomers in the organic
phase was calculated by the subtractive method. Each experiment was conducted in trip-
licate and the standard deviation should be less than 3%. The mobile phase for ana-
lyzing H2A enantiomers was as follows: acetonitrile aqueous solution (20%, v/v)
containing 8 mmolÁL-1 HP-b-CD and 0.05% trifluoroacetic acid (v/v) at a flow of
1.0 mLÁmin-1. The UV spectrometer was operated at 254 nm, while the column tem-
perature was set at 25 °C. The injection volume was 20 lL [27]. The chromatograms are
Fig. 3 HPLC chromatograms of H2A: before and after solvent sublation
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shown in Fig. 3. The retention time of R-H2A was approximately 17.32 min while it was
about 19.16 min for S-H2A.
2.4 Theory of SS Enantioseparation
Partitioning and enantioselectivity, which are expressed in terms of the distribution
coefficient (D), separation factor (b) and enantiomer excess (e.e.%), are important
parameters to estimate the performance of SS enatioseparation. They can be calculated by
the following formulae:
initial ½RŠ or initial ½SŠ
DRðSÞ
¼
À 1
ð1Þ
½RŠ or ½SŠ
distribution ratio of S À enantiomer
b ¼
ð2Þ
ð3Þ
distribution ratio of R À enantiomer
½RŠðor½SŠÞ À ½SŠðor ½RŠÞ
e:e:% ¼
½RŠ þ ½SŠ
for which [ ] denotes a concentration (mgÁmL-1) of the enantiomer in the aqueous phase.
3 Results and Discussion
3.1 Influence of pH in the Aqueous Phase
Since pH impacts the existing form of H2A, stringent control of the pH is recommended in
all experiments. The effect of pH on distribution coefficients and enantioselectivities was
investigated with the H2A concentration 1.0 gÁL-1, HP-b-CD of 0.015 molÁL-1, L-DBTA
of 0.7 molÁL-1, the air flow rate of 30 mLÁmin-1, and sublation time of 2 h. It can be
inferred from Fig. 4 that increasing the pH from 2.5 to 5.0 caused the decreases of DR and
DS. The reason may be that increasing pH value makes the reaction equilibria move to the
right side [24].
Fig. 4 Influence of the pH on the distribution behavior. Initial concentrations of H2A enantiomers, L-
DBTA, and HP-b-CD: 1.0 gÁL-1, 0.70 molÁL-1, and 0.015 molÁL-1, sublation time 2 h and flow rate
30 mLÁmin-1
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H2A ꢀ Hþ þ HAÀ
HAÀ ꢀ Hþ + A2À
ð4Þ
ð5Þ
The amount of dissociated forms of H2A increased while that of molecular H2A
decreased with the rise of pH. HP-b-CD and L-DBTA mainly have chiral recognition
ability and affinity for molecular H2A, but not for dissociated H2A. Ionic species of H2A
only exist in the aqueous phase. The concentrations of complexes formed by selectors and
H2A enantiomers decreased with the increase of pH. When pH \ 2.5, D and b showed
almost no changes. Therefore, the pH value of 2.5 was adopted in further experiments.
3.2 Influence of Initial Concentration of H2A Enantiomers
The influence of the H2A enantiomer concentrations on enantioseparation efficiency was
investigated as shown in Fig. 5 with the other experimental conditions being the same as
those for studying the effect of pH. It can be seen that all of the distribution coefficients
increased with the increases in the initial concentration of H2A enantiomers. This can only
be caused by non-selective partitioning. However, the values of enantioselectivities
increased before the H2A concentration reached 1.0 gÁL-1 and then decreased with a
further increase of the H2A concentration. This was due to the fact that, at low concen-
trations, most selectors action was through enantioselective complexation and, at higher
concentrations, more non-selective partitioning was occurring. Therefore, 1.0 gÁL-1 was
the optimized H2A concentration for this system.
3.3 Influence of Concentration of HP-b-CD
The influence of HP-b-CD concentration was investigated by varying the HP-b-CD con-
centration from 0.0025 to 0.02 molÁL-1 with other parameters being held constant. The
results are depicted in Fig. 6. As can be seen, D decreased remarkably as the concentration
of HP-b-CD increased to 0.015 molÁL-1. Meanwhile, the opposite tendency was observed
for b and e.e.%, indicating improved chiral separation ability. The reason may be that, with
Fig. 5 Influence of the initial concentration of H2A enantiomers on the distribution behavior. Initial
concentrations of L-DBTA and HP-b-CD: 0.70 and 0.015 molÁL-1, pH = 2.5, sublation time 2 h and flow
rate 30 minÁL-1
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Fig. 6 Influence of HP-b-CD concentration on the distribution behavior. The concentrations of H2A
enantiomers and L-DBTA: 1.0 gÁL-1 and 0.70 molÁL-1, pH = 2.5, sublation time 2 h and flow rate
30 mLÁmin-1
increasing HP-b-CD concentration more complexes formed in aqueous phase that did not
dissolve in the organic phase. So, under the same operation conditions, fewer H2A
molecules were transported to the organic phase and this resulted in the decrease of D. Due
to the preferential recognition for R-H2A by HP-b-CD, DR decreased more than DS cor-
responding to the increase of b and e.e.%. When the selector concentration was increased
from 0.015 to 0.025 molÁL-1, D continued to decrease with the reason being the same as
above. However, the decrease of b and e.e.% should be attributed to the increasing
amounts of complexes formed by HP-b-CD and S-H2A compared to those formed by HP-
b-CD and R-H2A in the SS process when excess HP-b-CD is present. Therefore, the
difference of concentrations between the two enantiomers at aqueous or organic phase
diminished.
Fig. 7 Influence of the concentration of L-DBTA on the distribution behavior. The concentrations of H2A
enantiomers and HP-b-CD: 1.0 gÁL-1 and 0.015 molÁL-1, pH = 2.5, sublation time 2 h and flow rate
30 mLÁmin-1
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3.4 Influence of Concentration of L-DBTA
The influence of L-DBTA concentration on enantioseparation behavior is summarized in
Fig. 7 with the other experimental conditions being the same as those for studying the
effect of pH. With the increase of L-DBTA concentration, the distribution coefficients were
greatly increased. Meanwhile, the enantioselectivities all increased until the concentration
of L-DBTA was 0.70 molÁL-1. The reason is that, with the increase of L-DBTA con-
centration, more complexes H2A and L-DBTA formed in the organic phase. So, at the same
operation conditions, more H2A molecules were transported to the organic phase and
resulted in the increase of D. Due to the preferential recognition for S-H2A by L-DBTA, DS
increased more than DR leading to the increase of b and e.e.%. When the concentration of
L-DBTA was increased further, D continued to increase for the same reason as above,
whereas the enantioselectivities followed the opposite trend. This was because greater
amounts of complexes are formed by L-DBTA and R-H2A than are formed by L-DBTA
and S-H2A in the SS process when excess L-DBTA is present. As a result, the difference of
concentrations between the two enantiomers in the aqueous or organic phases was
diminished.
3.5 Influence of the Air Flow Rate
Figure 8 shows the effect of varying the air flow rate on SS for the separation of H2A
enantiomers. The air flow rate was examined in the range of 10–50 mLÁmin-1, which
could significantly influence the velocity of mass transfer of H2A between the aqueous and
organic phases. Generally, the rate of gas–liquid interfacial area generation can be
increased by increasing the air flow rate. However, a too high flow rate should be avoided
because a turbulent mixing may occur at the interface between the organic and aqueous
phases. Such mixing can promote the redissolution of the floated product in the aqueous
phase. In actual operation, the two-phase interface area increased until the air flow rate was
up to 30 mLÁmin-1 but then the two phase interface decreased with the increase of air flow
rate. From these experimental results, the air flow rate was finally fixed at 30 mLÁmin-1
.
Fig. 8 Influence of the air flow rate on the distribution behavior. The concentrations of H2A enantiomers,
L-DBTA and HP-b-CD: 1.0 gÁL-1, 0.70 molÁL-1 and 0.015 molÁL-1, pH = 2.5 and sublation time 2 h
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3.6 Influence of the Sublation Time
The effect of the sublation time on the enantioseparation is listed in Fig. 9. The results
suggest that the distribution coefficients and enantioselectivities increase rapidly for
sublation times less than 2 h but then tended to smooth out at longer times. This was
because the interphase force and the contact area of the interphase increase when the
sublation time is extended, in which cases the distribution coefficients and enantiose-
lectivities show an increase and finally reach equilibrium. Therefore, the sublation time
was fixed at 2 h.
3.7 Comparison of Single Selectors and Collaborative Selectors in the SS
System
Under the optimal conditions, H2A was separated by the new SS system, while, at the same
time, the SS system with HP-b-CD or L-DBTA as a single selector were also analyzed for
comparison. As we designed in our experiments, when 0.015 molÁL-1 HP-b-CD was used
as single selector in SS system, there was no L-DBTA in the system. The situation of L-
DBTA as a single selector was analogous to that for HP-b-CD. Compared the results
shown in Table 1, it was found that the SS system with collaborative selectors has a much
stronger chiral separation ability than that with a single selector. Obviously, this should be
attributed to the combination of the enantioseparation abilities of both HP-b-CD and L-
DBTA.
3.8 Reasonable Enantioseparation Mechanisms
Enantioseparation mechanisms are of critical importance for understanding and optimizing
a chiral separation process. As a result, the possible mechanisms for H2A enantioseparation
by the SS method with collaborative chiral selectors were explored systematically in our
work. H2A is a type of binary acid with two ionization equilibria being present:
Fig. 9 Influence of sublation time on the enantioseparation. The concentrations of H2A enantiomers, L-
DBTA and HP-b-CD: 1.0 gÁL-1, 0.70 molÁL-1 and 0.015 molÁL-1, pH = 2.5 and flow rate 30 mLÁmin-1
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Table 1 Comparison between
single selectors and collaborative
selectors in SS systems
Items Collaborative selectors
HP-b-CD
L-DBTA
AVG
S
AVG
S
AVG
S
DR
DS
b
1.19
2.95
2.47
0.0306
0.0300
0.0781
1.0214
0.59
0.77
1.31
5.90
0.0265
0.0400
0.0833
6.12 0.1060
8.45 0.1114
1.38 0.0208
e.e.% 29.50
1.0137 13.82 0.8293
H2A Kꢀa1 Hþ + HAÀ
ð6Þ
ð7Þ
Ka2
HAÀ ꢀ Hþ + A2À
The most plausible enantioseparation mechanisms that mainly influence the distribution
coefficient and selectivity of H2A enantiomers in the sublation process can be explained by
the following equations:
K1
ðH2A)a þ HP-b-CD ꢀ H2A À HP-b-CD
K2
ð8Þ
ð9Þ
HAÀ þ HP-b-CD ꢀ ðHA À HP-b-CDÞÀ
K3
2À
A
2À þ HP-b-CD ꢀ ðA À HP-b-CDÞ
K4
ð10Þ
ð11Þ
ð12Þ
ðH2AÞo þ L-DBTA ꢀ H2A À L-DBTA
K5
HAÀ þ L-DBTA ꢀ ðHA À L-DBTAÞÀ
K6
2À
A
2À þ L-DBTA ꢀ ðA À L-DBTAÞ
ð13Þ
ð14Þ
ðH2A)o ꢀ ðH2A)a
where (H2A)a, (H2A)o represent H2A in the aqueous phase and organic phases, respec-
tively. The new SS enantioseparation process includes three steps. In the first step, some
H2A enantiomers are complexed by HP-b-CD, as expressed in Eqs. 8–10. To be empha-
sized, HP-b-CD is inclined to recognize R-H2A preferentially in this process and the
stability of H2A - HP-b-CD was better than for other inclusion complexes [25]. In the
second step, the inclusion complexes and free H2A rose up with bubbles and was con-
centrated at the interface between the aqueous and organic phases. The third step took
place when the bubbles reached the interface, releasing of the molecules. The solubility of
complexes formed by H2A and HP-b-CD is poor in the organic phase, where H2A has
better solubility than in the aqueous phase. So, the free H2A enantiomers were transported
to the organic phase and interacted with L-DBTA, as expressed in Eqs. 11–13. Note that,
L-DBTA recognized S-H2A preferentially in this process and the stability of H2A - L-
DBTA was better than for other complexes. From the considerations of the first and third
steps, the amount of S-H2A in the transport process was greater than for R-H2A. Conse-
quently, more S-H2A was concentrated in the organic phase after the sublation process and
enantioseparation was thus achieved.
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4 Conclusion
In this work, a solvent sublation (SS) system using dibenzoyl-L-tartaric acid (L-DBTA) and
hydroxypropyl-b-cyclodextrin (HP-b-CD) as collaborative selectors was introduced for
separating phenylsuccinic acid (H2A) enantiomers. Hydrophobic L-DBTA and hydrophilic
HP-b-CD preferentially recognize S-H2A and R-H2A, respectively. Different factors that
influence the final enantioselectivity were investigated. Under the optimized conditions:
H2A concentration 1.0 gÁL-1, HP-b-CD 0.015 molÁL-1, L-DBTA 0.70 molÁL-1, pH = 2.5
in the aqueous phase, air flow rate of 30 mLÁmin-1 and sublation time of 2 h, the sepa-
ration factor (b) and enantiomer excess (e.e.%) values reached 2.47 and 29.50%, respec-
tively, and yields of R-H2A and S-H2A were 0.23 and 0.13 gÁL-1, also respectively.
What’s more, by combining the advantages of SS and recognization abilities of chiral
selectors, this new enantioseparation method can be also employed for the separation of
other hydrophobic enantiomers through optimizing of the compositions of the SS system,
the kinds of chiral selectors and other related sublation parameters. In conclusion, the
explorations in our study will further enrich the enantioseparation methods and pave a way
for the application of SS in the chiral separation field.
Acknowledgements This work was supported by the National Natural Science Foundation of China (No.
21476269).
References
1. Maier, N.M., Franco, P., Lindner, W.: Separation of enantiomers: needs, challenges, perspectives.
J. Chromatogr. A 906, 3–33 (2001)
2. Ribeiro, A.E., Gomes, P.S., Pais, L.S., Rodrigues, A.E.: Chiral separation of ketoprofen enantiomers by
preparative and simulated moving bed chromatography. Sep. Sci. Technol. 46, 1726–1739 (2011)
3. Jiao, F., Yang, W., Huang, D., Yu, J., Jiang, X., Chen, X.: Enantioseparation of ofloxacin enantiomers
by mixed extractants in biphasic system. Sep. Sci. Technol. 47, 1971–1976 (2012)
4. Lee, N.H., Frank, C.W.: Separation of chiral molecules using polypeptide-modified poly vinylidene
fluoride membranes. Polymer 43, 6255–6262 (2002)
5. Tong, S., Yan, J.: Enantioseparation of phenylsuccinic acid by high speed counter-current chro-
matography using hydroxypropyl-b-cyclodextrin as chiral selector. J. Chromatogr. A 1218, 5602–5608
(2011)
6. Rmaile, H.H., Schlenoff, J.B.: Optically active polyelectrolyte multilayers as membranes for chiral
separations. J. Am. Chem. Soc. 125, 6602–6603 (2003)
7. Wang, L.J., Hu, S.Q., Guo, Q.L., Yang, G.L., Chen, X.G.: Di-n-amyl l-tartrate–boric acid complex
chiral selector in situ synthesis and its application in chiral nonaqueous capillary electrophoresis.
J. Chromatogr. A 1218, 1300–1309 (2011)
8. Jiao, F., Chen, X., Wang, Z.: Enantioselective extraction of racemic mandelic acid by di(2-ethyl-
hexyl)phosphoric acid and tartaric acid derivatives as mixed complex chiral selectors. Solvent Extr. Ion
Exch. 27, 447–458 (2009)
9. Gensheng, Y., Li, Y., Zhimin, O.U., Yao, S.J.: Resolution of ibuprofen ester by catalytic antibodies in
water-miscible organic-solvents. Chin. J. Chem. Eng. 17, 506–512 (2009)
10. Chen, X., Dong, Q., Yu, J., Jiao, F.: Extraction of tryptophan enantiomers by aqueous two-phase
systems of ethanol and (NH4)2SO4. J. Chem. Technol. Biotechnol. 88, 1545–1550 (2013)
11. Wang, J., Yang, H., Yu, J., Chen, X., Jiao, F.: Macrocyclic b-cyclodextrin derivative-based aqueous-
two phase systems: phase behaviors and applications in enantioseparation. Chem. Eng. Sci. 143, 1–11
(2016)
12. Sun, X., Chang, Z., Shen, S., Hu, X., Liu, H.: Effects of emulsion properties on recovering butyl acetate
from wastewater of penicillin plant by solvent sublation. Colloids Surf. A 286, 8–16 (2006)
13. Cheng, Q., Dong, H.: Solvent sublation using dithizone as a ligand for determination of trace elements
in water samples. Mikrochim. Acta 150, 59–65 (2005)
123

2170
J Solution Chem (2017) 46:2159–2170
14. Wu, Z., Liang, B., Hu, B., Zheng, H.: Separation of L-lysine by solvent sublation. Sep. Purif. Technol.
66, 237–241 (2009)
15. Jiao, F., Yang, W., Wang, F., Tian, L., Li, L., Chen, X.: Enantioseparation of racemic mixtures based on
solvent sublation. Chirality 24, 661 (2012)
16. Chen, X., Yang, W., Jiang, X., Jiao, F., Tian, L.: Enantioseparation of a-cyclohexylmandelic acid by
solvent sublation. Tetrahedron Asymmetry 23, 1227–1233 (2012)
17. Li, L., Jiao, F.P., Jiang, X.Y., Tian, L.X., Chen, X.Q.: Resolution of racemic ofloxacin based on co-
technology of bubble fractionation and extraction. Chromatographia 73, 423–429 (2011)
18. Bayati, F., Shayegan, J., Noorjahan, A.: Treatment of oilfield produced water by dissolved air pre-
cipitationsolvent sublation. J. Pet. Sci. Technol. 80, 26–31 (2011)
19. Bi, P.Y., Dong, H.R., Guo, Q.Z.: Separation and purification of penicillin G from fermentation broth by
solvent sublation. Sep. Purif. Technol. 65, 228–231 (2009)
20. Dong, H.R., Bi, P.Y., Wang, S.H.: Separation and enrichment of Baicalin in SBG by solvent sublation
and its determination by HPLC and spectroscopy. Anal. Lett. 38, 257–270 (2005)
21. Li, M., Dong, H.: The investigation on the aqueous two-phase floatation of lincomycin. Sep. Purif.
Technol. 73, 208–212 (2010)
22. Lobacheva, O.L., Dzhevaga, N.V., Chirkst, D.E.: Solvent sublation of cerium ions from dilute aqueous
solutions. Russ. Chem. Bull. 61, 962–965 (2012)
23. Lobacheva, O.L., Berlinskii, I.V., Cheremisina, O.V.: Solvent sublation and ion flotation in aqueous salt
solutions containing Ce III and Y III in the presence of a surfactant. Russ. J. Appl. Chem. 87,
1863–1867 (2014)
24. Chen, X., Yang, W., Jiang, X., Jiao, F., Tian, L.: Enantioseparation of a-cyclohexylmandelic acid by
solvent sublation. Tetrahedron Asymmetry 23, 1227–1233 (2012)
25. Xing, J., Li, F.: Chiral separation of mandelic acid by temperature-induced aqueous two-phase system.
J. Chem. Technol. Biotechnol. 87, 346–350 (2012)
26. Chen, X., Liu, L., Jiao, F., Wang, Z.: Extraction of phenylalanine enantiomers by aqueous two-phase
systems containing combinatorial chiral selector. Chin. J. Chem. 30, 965–969 (2012)
27. Zhuang, J., Yang, W., Chen, X., Jiao, F.: Enantioseparation of phenylsuccinic acid enantiomers using
aqueous two-phase flotation and their determination by HPLC and UV detection. Chromatographia 77,
679–685 (2014)
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