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Published on the web February 5, 2011
Separation of Naproxen Enantiomers Using Hollow Fiber
Molecularly Imprinted Membrane Chromatography
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1
1
1
1
2
Nai Ci Bing,* Zhen Tian, Hai Ying Jin, Li Jun Wang, Lu Ping Zhu, and Zhen Liang Xu
1
School of Urban Construction and Environmental Engineering, Shanghai Second Polytechnic University,
Shanghai 201209, P. R. China
2
Chemical Engineering Research Center, East China University of Science and Technology,
130 Meilong Road, Shanghai 200237, P. R. China
(
Received December 6, 2010; CL-101032; E-mail: ncbing@eed.sspu.cn)
In this paper, the use of molecularly imprinted membrane
MIM) for chromatographic separation is described. Poly(vinyl-
1
(
Imprinted
polymer
layer
idene fluoride) hollow-fiber membranes were grafted on an
imprinted polymer layer by using 4-vinylpyridine and trimeth-
ylolpropane triacrylate as monomer and crosslinker and were
applied as the chromatographic media. During separation,
naproxen enantiomers were separated efficiently, and the
separation factor was 2.36. Molecularly imprinted membrane
chromatography (MIMC) showed an apparently opposite trans-
port behavior compared to molecularly imprinted polymer
Template-
S-naproxen
2
UV-
detector
Membrane module
a
Pump
and
injector
(MIP)-packed chromatography.
b
Chromatography has been extensively applied in purifica-
tion, separation, and analysis owing to good selectivity,
efficiency, and high loading capacity. However, separation is
limited by using packed beads in this process. For example, high
pressure drop, intraparticle diffusion, and channeling lead to
increased process time, recovery liquid volume, and complicated
Figure 1. Experimental setup for chromatographic measure-
ment: (a) Schematic illustration of MIMC with hollow-fiber
module and (b) SEM images of cross section of membrane
(
1: initial membrane, 2: imprinted membrane).
1
scale-up. By using membranes as chromatographic media, some
trimethylolpropane triacrylate as template, monomer and
crosslinker (molar ratio = 1:4:20) copolymerization in the
surface of poly(vinylidene fluoride) hollow-fiber membranes
(Figure 1 b-1; self-made; porosity: 70%, pure water flux:
of the major limitations associated with column chromatography
can be resolved because of tremendous decrease of mass-transfer
2
resistance. Membranes were first introduced into affinity
3
¹2 ¹1
¹1
chromatography by Brandt in 1988. Since then, membrane
12 L m
h
bar , molecular weight cutoff with BSA67000
chromatography has become a fast growing bioseparation
technique.
as a standard solution: 94.7%). After elution with acetic acid/
methanol (1:9, v/v) and methanol, respectively, they were made
into hollow-fiber modules.
4
Molecular imprinting is a technique to prepare crosslinked
polymers with highly selective recognition sites for a given
target or group of target molecules. With the development of
Chromatographic media is one of the most important factors
of separation efficiency. So hollow fiber molecularly imprinted
membrane (MIM) plays a key role in MIMC. Seen from
Figure 1b, an imprinted polymer layer deposited on the surface
of initial membranes and remedied the defects of the membrane
surface. At the same time, both a linear path through the
membrane and the cylindrical channels are still apparent and
interspersed inside the MIM similar to the initial membrane.
The enantioselective separation by MIMC was determined
as illustrated in Figure 1. The resulting chromatograms of
racemic naproxen and S-naproxen are shown in Figure 2. MIMC
facilitated the resolution of naproxen enantiomers, and a
separation factor (¡) of 2.36 was obtained. Here, ¡ is defined
as the relationship ¡ = K /K , where K and K are the capacity
5
imprinted membranes, which are obtained by combination of
molecular imprinting technology and membrane separation,
molecularly imprinted membrane chromatography (MIMC) as a
special affinity chromatography is considered to realize separa-
tion and purification of given molecules with higher selectivity
and efficiency.
In this paper, hollow fiber MIMC is developed and applied
to the separation of naproxen enantiomers. We focus on detailed
investigations of the morphology of imprinted membranes,
separation efficiency of hollow fiber MIMC, and transport
behavior compared to molecularly imprinted polymers (MIPs) as
stationary phase in HPLC experiments.
R
S
R
S
Figure 1a shows a schematic diagram of MIMC. Analytes
are pumped into the hollow fiber molecularly imprinted
membrane modules (8 mm © 150 mm stainless steel pipe), and
permeation solutions are monitored by a UVD-680-1-UV
spectrometer detector (Shanghai Kingdom Biochemical Instru-
ment Factory) system. Imprinted membranes (Figure 1 b-2)
were obtained by taking S-naproxen, 4-vinylpyridine, and
factor of the R and S enantiomer, respectively. The capacity
factors were determined according to KR = tR/t0 ¹ 1 and
K = t /t ¹ 1, where t and t are the retention times of the R
and S enantiomer, respectively, and t0 is the retention time of the
dead volume, which was determined by the injection of toluene.
As shown in Figure 2, there was usually extensive peak
broadening and asymmetry in the MIMC, which was mainly due
S
S
0
R
S
Chem. Lett. 2011, 40, 266267
© 2011 The Chemical Society of Japan