Fabrication and Evaluation of Artemisinin-Imprinted Composite

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Fabrication and Evaluation of Artemisinin-Imprinted Composite Membranes by Developing a Surface Functional Monomer-Directing Prepolymerization System Yilin Wu, Ming Yan, Yongsheng Yan, Xinlin Liu, Minjia Meng, Peng Lv, Jianming Pan, Pengwei Huo, and Chunxiang Li Langmuir, Just Accepted Manuscript • Publication Date (Web): 24 Nov 2014 Downloaded from http://pubs.acs.org on November 25, 2014

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Fabrication and Evaluation of Artemisinin-Imprinted Composite Membranes by Developing a Surface Functional Monomer-Directing Prepolymerization System

Yilin Wu,a Ming Yan,a Yongsheng Yan,a Xinlin Liu,b Minjia Meng,a Peng Lv,c Jianming Pan,a Pengwei Huo,a Chunxiang Lia,*

a

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China

b

School of Energy and Power Engineering, Jiangsu University, Zhenjiang 212013, China

c

School of Material Science and Engineering, Jiangsu University, Zhenjiang 212013, China

* Corresponding author E-mail: [email protected] Telephone Number: +86 0511-88790683; fax: +86 0511-88791800

1

ACS Paragon Plus Environment

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ABSTRACT Inspired by a surface functional monomer-directing prepolymerization system, a straightforward and effective synthesis method was first developed to prepare highly regenerate and perm-selective molecularly imprinted composite membranes of artemisinin (Ars) molecules. Attributing to the formation of prepolymerization system, Ars molecules are attracted and bound to the membrane surface, hence promoting the growth of homogeneous and high-density molecular

recognition

sites

on

the

surface

of

membrane

materials.

Afterward,

a

two-step-temperature imprinting procedure was carried out to prepare the novel surface functional monomer capping molecularly imprinted membranes (FMIMs). The as-prepared FMIMs not only exhibited highly adsorption capacity (11.91 mg g-1), but also showed an outstanding specific selectivity (imprinting factor α is 4.50) and excellent perm-selectivity ability (separation factor β is 10.60) toward Ars molecules, which is promising for Ars separation and purification.

KEYWORDS: Molecularly Imprinted Membranes, Composite Materials, Prepolymerization System, Artemisinin, Selective Recognition and Separation

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INTRODUCTION Membrane technology as a simple, low-cost and efficient method has been extensively used in many separation process, such as water purification, desalination and oily wastewater treatment.1-3 It has also caused great repercussions not only in bioscience, but also in the life sciences.4 However, because of many technically challenging issues such as selective separation ability, numerous specific recognition ability and separation issues cannot be solved with traditional separation membranes. Hence, in order to further develop the intelligent membranes with highly specific recognition ability and permselectivity for individual compounds, combination of the molecularly imprinted and membrane technology is of great interest. Molecularly imprinted technique (MIT) allows formation of specific recognition sites in synthetic polymers and has received much attention in the past four decades.5 Molecularly imprinted polymers (MIPs) are usually prepared by copolymerization of functional monomers and cross-linkers

in

the

presence

of

template

molecules.6-9

Because

of

the

excellent

mechanical/chemical stability, flexibility in choosing polymerizing monomers, and ease of preparation, MIPs also keep considerable potential applications in catalysis, environmental monitoring, and medical diagnostics.10-16 However, conventional imprinting polymer materials often possess excellent selectivity but low regeneration and poor permselectivity to template molecules. Thus, it is a challenging task to search for a straightforward and powerful synthetic material, which possesses high density of specific recognition sites and excellent permselectivity. Molecularly imprinted membranes (MIMs) are the membranes either composed of MIPs or containing MIPs. Combination of MIT and membrane technology provides the membranes with specific selectivity and permselectivity for separating template molecules.17-19 Nowadays, MIMs with higher chemical selectivity and rebinding capacity for target molecules that offer high flux of target molecules are required. However, it is a general issue that the coinstantaneous and stochastic creation of imprinting sites during the imprinting polymerization process, which limits the regeneration and permselectivity of MIMs. To solve these problems, several template controlled methods have been investigated, such as film graft imprinting, surface imprinting, and monomolecular dendritic imprinting.20-22 In this work, we develop a surface functional monomer-directing prepolymerization system for highly dense imprinting of target species at the surface of regenerated cellulose membranes 3


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(RCMs). The excellent antimalarial drug recommended by World Health Organization,23-25 artemisinin (Ars), is used as template molecule. The adsorption capacity of the as-prepared surface functional monomer capping molecularly imprinted membranes (FMIMs) is nearly 6 times than that of normal imprinting membranes.26 The excellent selectivity and perm-selectivity ability toward Ars molecules also made the FMIMs as a good candidate for Ars separation and purification. To our best knowledge, it is the first time to incorporate the surface monomer-directing prepolymerization method into MIMs. This research is also helpful to understand the imprinting effect and recognition mechanism in membrane separation performance. The method reported here can also direct many applied science not only in MIT, but also in the synthesis of any other functional modified surfaces in membrane science and technology.

EXPERIMENTAL SECTION Materials. Regenerated cellulose membranes (RCMs) (average pore diameter of 0.45 µm, 25 mm in diameter, 100 µm thick, Sartorius). Artemisinin (Ars, 98%, Aladdin), artemether (98%, Aladdin), ethylene glycol dimethacrylate (EGDMA, 98%, Aladdin), aminopropyltriethoxysilane (APTES, 99%, Aladdin), acryloyl chloride (98%, Aladdin), Azo-bis-isobutryronitrile (AIBN, 99%, Aladdin), acrylamide (AM, 99%, Aladdin) were used as received. All chemicals used in the synthetic process were analytical grade. Instruments. The morphologies of modified membranes and FMIMs were examined by scanning electron microscopy (SEM, S-4800). X-ray photoelectron spectroscopy (XPS) were recorded using a monochromatized Al Kα X-ray source with an ESCALAB 250 spectrometer. High-performance liquid chromatography (HPLC, Agilent 1200) equipped with a UV-vis detector (Palo Alto) was used for the determination of Ars and artemether. Chemical Modification of Regenerated Cellulose Membranes (RCMs). A two-step process was carried out to obtain the AM monomers capping RCMs (AM-APTES-RCMs). Firstly, RCMs were chemically modified using 3-aminpropyltriethoxylsilane (APTES) to obtain an aminopropyl monolayer on the surface of RCMs. Briefly, 3.0 pieces of RCMs and 2.0 mL of APTES were added into 50 mL of anhydrous toluene and simultaneously stirred in the protection of nitrogen at 50 oC for 12 h, and triethylamine was used as a catalyst. The products were washed with toluene for several times, and dried to constant weight in vacuum at 50 oC. Then the APTES-modified 4


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RCMs were further modified by acryloyl chloride to obtain the AM-APTES-RCMs. Briefly, 1.0 mL of acryloyl chloride, 2.0 pieces of APTES-RCMs were added to 50 mL of anhydrous toluene, and then anhydrous K2CO3 (10 mg) was added to the above reaction as a catalyst. The reaction system was stirred for 10 h in the protection of nitrogen at 25 oC. After that, the modified membranes were separated by washed with toluene and ethanol. Finally, the obtained AM-APTES-RCMs were dried in vacuum at 45 oC. Imprinting of Ars Molecules at Surface of AM-APTES-RCMs. Before conducting an imprinting polymerization, Ars (15 mg), acrylamide (AM, 0.1 mmol), and 2.0 pieces of AM-APTES-RCMs were dispersed in 50 mL of acetonitrile in an incubating shaker. After ultrasonic processing for 30 min, the mixture was sealed for 24 h in dark to prompt the template molecules, functional monomers, and the AM at the surface of AM-APTES-RCMs to form a stable prepolymerization system. After that a mixture of EGDMA (0.4 mmol) and AIBN (8 mg) was added to the above complex system. The prepolymerization reaction system was purged by bubbling nitrogen through the solution for 15 min at room temperature. And then the two-step-temperature copolymerization procedure was carried out under stirring (350 rpm). Firstly, the mixture reacted at for 5 h under stirring at 50 oC, and then the second polymerization procedure was accomplished at 60 oC for 24 h. Following this polymerization procedure, the surface functional monomer capping molecularly imprinted membranes (FMIMs) were obtained. And then, the FMIMs were rinsed with ethanol and deionized water. And then the as-prepared FMIMs were purified with the mixture of ethanol/acetic acid (9:1, v/v) to remove the template molecules Ars by Soxhlet extraction, followed by ethanol, until no Ars molecules could be detected by HPLC. In the end, the purified FMIMs were dried in a vacuum drying chamber at 45 o

C. The surface functional monomer capping non-imprinted membranes (FNIMs) were prepared

without the addition of template molecules and subjected to the same procedure. Batch Binding Experiments. The impact of experiment parameters (contact time and initial concentration of Ars) on the adsorption behavior of Ars were studied by batch binding mode. In adsorption isotherm experiments, one piece of FMIMs or control FNIMs was added to 10 mL of Ars ethanol solutions of different concentrations (0.08, 0.2, 0.3, 0.4, 0.8 mg mL-1). The mixture was shaked in thermostatic water bath at 25 oC for 3 h. And then, the equilibrium concentrations were determined by HPLC at 217 nm. The adsorption amounts were calculated by the following 5


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equation:

ܳ௘ =

（஼బ ି஼೐ ）௏

(1)

௠

where Qe (mg g-1), C0 (mg mL-1), and Ce (mg mL-1) represent the equilibrium adsorption capacity, initial concentration of Ars and the concentration of Ars after adsorption, respectively. V is the volume of solution, and m is the weight of FMIMs or FNIMs. The adsorption kinetics studies were investigated as follow, one piece of FMIMs or control FNIMs was added to 10 mL of Ars solution (400 mg L-1) at 25 oC, and the samples were taken out at predetermined time intervals. The experimental adsorption capacity of Ars (Qt, mg g-1) was calculated according to:

ܳ௧ =

(஼బ ି஼೟ )௏

(2)

௠

where Ct (mg L-1) is the concentration of Ars solution at different time t. Evaluating Selectivity and Regeneration of FMIMs. The selectivity of the FMIMs was investigated using artemether as comparative molecules with the initial concentrations of 0.08, 0.2, 0.3, 0.4, 0.8 mg mL-1, respectively. The selective binding experiments were carried out at 25 oC for 3.0 h. Figure 1 represents the chemical structures of Ars and artemether. The imprinting factors α were calculated by the following equation:

α=

ொಾ

(3)

ொಿ

where QM and QN are the adsorption amounts of FMIMs and FNIMs at different initial concentrations of Ars. To investigate the regeneration and stability character of FMIMs, the regenerate adsorption experiments were performed at the concentration of 400 mg L-1 five times by the same adsorbing membrane. After adsorption, the saturated adsorbed FMIMs were eluted with the mixture of methanol and acetic acid (9:1, v/v) by Soxhlet extraction to remove the target molecules. And then the regenerated FMIMs were used for subsequent adsorption cycles (adsorption/desorption). Selectivity Permeation Experiments. The selectivity permeation performances of FMIMs or FNIMs were studied by competitive permeability tests toward different targets (Ars and artemether). The mixture solutions consisted of 200 mg L-1 of Ars and artemether ethanol mixed solution was used as feeding solution. The permeation experiments were carried out using the H-model tube installation (Figure S1) as we have reported.26 The concentrations of Ars and 6


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artemether from receiving phase that permeated through the FMIMs or FNIMs were detected by HPLC. In addition, the mixture solutions in both chambers were kept homogeneous by gas bath thermostatic oscillator at 25 oC. The permeation flux J (mg cm-1 s-1), permeability coefficient P (cm2 s-1) and perm-selectivity factor βartemether/Ars are obtained as follows:

‫ܬ‬௜ = ܲ=

∆஼೔ ௏ ∆௧஺ ௃೔ ௗ (஼ಷ೔ ି஼ೃ೔ )

i = Ars, artemether

(4)

i = Ars, artemether

(5)

ߚ௔௥௧௘௠௘௧௛௘௥/஺௥௦ =

௉ೌೝ೟೐೘೐೟೓೐ೝ

(6)

௉ಲೝೞ

where V, A, and d represent the volume of feeding and receiving solutions (mL), effective membrane area (cm2), and the membrane thickness, respectively. △Ci/△t is the change of concentration in the receiving solution. (CFi-CRi) is the concentration difference between feeding and receiving solutions.26

RESULTS AND DISCUSSION Preparation of Prepolymerization System. The key design in our FMIMs is the functional monomer modification at the surfaces of membranes. In this work, the imprinting procedure at the surface of RCMs was accomplished through a straightforward chemical modification of stable amide groups and vinyl monomers, and then copolymerization with the cross-linking agents and functional monomers. Figure 2 illustrates the prepolymerization system in the presence of Ars, AM, and AM-APTES-RCMs. AM was adopted to be functional monomer because of the consideration that the aminopropyl of AM and the lactone group of Ars could provide strong hydrogen-binding sites, which may direct the occurrence of specific recognition sites of Ars molecules in the imprinting procedure. Therefore, this surface functional monomer-directing prepolymerization system could not only drive the target species enriched onto the surface of RCMs, but also direct the selective imprinting copolymerization at the surface of RCMs at the same time. Procedures of Molecular Imprinting at Surface of AM-APTES-RCMs. The preparation of FMIMs is shown schematically in Figure 2. As shown in Figure 2, this study focused on the application of MIT in the synthesis of Ars-imprinted composite membranes at the surface of functional monomer capping RCMs. A two-step chemical modification was carried out to obtain 7


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the AM-APTES-RCMs. First, the pure RCMs were chemically modified with APTES at 50 oC for 12 h. And then the resultant APTES-RCMs were grafting with acryloyl chloride in the presence of K2CO3 in anhydrous toluene, leading to the creation of AM-APTES monolayer. To design the imprinting system, the copolymerization of functional monomers and cross-linking agents on the surface of AM-APTES-RCMs was carried out to prepare the FMIMs. The copolymerization of AM-APTES layer with functional monomers at the surface of RCMs can direct stereochemically complementary to the target compounds in the FMIMs, resulting in the creation of uniform imprinting polymer layer. As a result, after the removal of Ars molecules from FMIMs, the FMIMs with specific recognition and selectivity of Ars were obtained. Characterization of FMIMs. As a high-sensitivity surface analytical tool, XPS was used to analyze the chemical composition of different membranes. Figure 3 shows the XPS spectra of pure RCMs (a), APTES-RCMs (b), AM-APTES-RCMs (c), and FMIMs (d). As shown in Figure 3, after APTES modification of the RCMs, the intensity of O1s and C1s peaks of APTES-RCMs enhances, and new N1s, Si2s, and Si2p peaks emerge, indicating the formation of an APTES layer on the RCMs surface. After AM modification reaction, AM-APTES-RCMs displayed the characteristic peaks of C=C groups, as indicated with arrows. As evident in Figure 3c and 3d, FMIMs displayed relatively weak peaks of Si2s and Si2p comparing with the XPS data of AM-APTES-RCMs, and the intensity of N1s and O1s peaks enhance a lot, indicating the formation of the molecularly imprinted layer on the surface of the RCMs. In addition, as shown in norrow scan for C1s peaks for FMIMs, both C=O and C-O groups displayed stronger peaks comparing with AM-APTES-RCMs, implying the formation of imprinted polymer layers on the RCMs surface. Figure 4 summarizes the morphological characterization of various prepared membranes by SEM. As shown in Figure 4a, pristine RCMs showed a more smooth and porous structure. Compared with pristine RCMs, APTES-RCMs (Figure 4b) displayed a relative rough surface morphology. After formation of AM-APTES monolayer at the surface of RCMs, an AM-APTES monolayer could be seen in the AM-APTES-RCMs (Figure 4c). In Figure 4d, the creation of smaller and irregular pores is observed from FMIMs. And the surfaces of FMIMs are much rougher than that of RCMs. Compared with the other modified membranes, the change of surface morphology of FMIMs indicated the creation of imprinting polymer layers onto the surface of 8


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RCMs. Binding Analysis of FMIMs. The Ars adsorption kinetic curves of FMIMs or FNIMs in predetermined time were shown in Figure 5. As evident in Figure 5, in the first 60 min, the FMIMs exhibited an obvious rapid adsorption rate of template molecules and reached nearly 90% of the equilibrium capacity. After the first period of 60 min, the kinetic curve slowly reached the adsorption equilibrium within 90 min. In contrast with that of FMIMs, the kinetic curve of FNIMs increased slowly in the whole adsorption process. The results reflected an obvious rapid adsorption dynamics for target species (Ars) to FMIMs in consideration of the normal imprinting materials often needed more than 180 min to reach the adsorption equilibrium.26-29 Furthermore, it had been demonstrated that FMIMs possessed a much faster mass transfer and higher equilibrium capacity than FNIMs. The rapid dynamics adsorption might derive from the presence of the plentiful high-affinity and empty recognition sites at the surface of FMIMs, which could also be attributed to the complete removal of Ars molecules. In other words, a large amount of specific recognition sites are in the proximity or at the surface of the FMIMs. In order to further investigate the rate-controlling mechanism of Ars on FMIMs, the binding data was fitted with the pseudo-first-order30 rate equation and pseudo-second-order31 rate equation. The pseudo-first-order rate equation is listed as follow:

Q୲

= ܳ݁ − ܳ݁ ݁−݇1 ‫ݐ‬

(7)

where Qe and Qt (mg g-1) are the amount of Ars molecules adsorbed on membranes at equilibrium and time t, respectively. k1 (min-1) is the rate constant of pseudo-first-order model. The pseudo-two-order rate equation is listed as follow:

Q୲ =

௞మ ொ೐మ ௧

(8)

ଵା௞మ ொ೟ ௧

where k2 is the rate constant of pseudo-two-order model. The linear regression and adsorption rate constants from two models were summarized in Table 1, and the fitting data (pseudo-two-order model) for the adsorption of Ars molecules were also shown in Figure 5. As shown, pseudo-second-order model (R2 > 0.99) kept a better fit than that of pseudo-first-order model for the adsorption of Ars, and the fitting values of Qe by pseudo-second-order model were also approximate to the experimental data. As a result, it could be seen that the adsorption kinetics of Ars was fitted well with pseudo-second-order kinetics model and the adsorption process and could 9


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be determined by the rate-limiting step. In order to study the adsorption performance with different modified membranes quantitatively, the adsorption isotherm experiments were carried out at the temperature of 25 oC. The binding isotherms of Ars onto FMIMs and FNIMs are shown in Figure 6. It can be seen that the FMIMs exhibited a much higher binding capacity of Ars than that of FNIMs, which may originate from the large number of sterically complementary imprinting cavities for template molecules on the surface of FMIMs. Additionally, the maximum adsorption capacity of FMIMs is 11.90 mg g-1, nearly five times higher than that of FNIMs. What is more, the adsorption capacity of FMIMs in this research was much higher than those of most molecularly imprinted membranes previously reported.32-33 This obviously strong sorption ability of FMIMs may also lie in the prepolymerization system on the surface of FMIMs which provides a great number of selective recognition sites for Ars molecules. To further investigate the adsorption mechanism, the nonlinear expression of Langmuir34 isotherm model was given by the following equation:

ܳ௘ =

௄ಽ ொ೘ ஼೐

(9)

ଵା௄ಽ ஼೐

where Qe (mg g-1) and Qm (mg g-1) represent the equilibrium amount and saturation adsorption capacity of template molecules, respectively. Ce (mg L-1) is the equilibrium concentration of Ars, KL (L mg-1) is the Langmuir constant. The calculated data of the adsorption isotherm experiments such as linear regression values and adsorption equilibrium constants are listed in Table 2. As shown in Figure 6, it could be seen that the Langmuir isotherm model fitted well with the experimental data (KL, 0.003945 L mg-1; R2, 0.9937), which might originate from the homogeneous distribution of imprinting layers on the FMIMs. Selectivity Analysis and Recognition Mechanism. To investigate the specificity of FMIMs, the competitive adsorption experiments were carried out for binding of Ars and artemether. The selectivity tests for the coexisting compound were carried out with the different concentration ranging from 80 to 800 mg L-1. As shown in Figure 7, FMIMs still exhibited a much higher adsorption capacity for Ars in the presence of artemether, which suggesting the competitive antibiotics could hardly affect the specific recognition of FMIMs. So, they had less chance to be adsorbed onto the FMIMs. In addition, the maximum α value (selectivity factor) in the

10


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competitive adsorption experiments was 4.5, indicating a high specificity and adsorption selectivity of the FMIMs toward target molecules. As a result, during the imprinting procedure, a great number of specific artificial recognition sites were created on the surface of FMIMs, so the target species could be strongly binding to FMIMs. But the specific imprinting cavities at the surface of FMIMs were not complementary to the competitive molecules (artemether). Perm-selectivity Analysis and Separation Mechanism of Ars. The perm-selectivity performance of the FMIMs was confirmed by the competitive permeation experiments at 25 oC in 3.0 h. The time-dependent perm-selectivity curves of FMIMs and FNIMs for different compound are described in Figure 8. As shown, the concentration of Ars through the FNIMs is much higher than that of FMIMs, indicating that the FMIMs exhibited a highly specific selectivity due to the existence of recognition sites. In addition, the as-prepared FMIMs also showed a much high rate for artemether than Ars. As a consequence, artemether molecules could hardly transfer continuously through the FMIMs. The permeability coefficients of artemether and Ars through FMIMs or FNIMs were summarized in Table 3. Compared with FNIMs, FMIMs showed smaller permeability for both artemether and Ars molecules as reported in the previous literature.35 Meanwhile, P value of artemether (5.09×10-5) for FMIMs was much higher than that of Ars (0.48×10-5). Moreover, FMIMs also exhibited higher specificity recognition ability than that of FNIMs according to the obtained values of βartemether/Ars (Table 3). It could be concluded that because of the stronger interaction between Ars molecules and FMIMs produced by the imprinting procedure, artemether molecules diffuses faster through FMIMs than that of Ars molecules. The results from perm-selectivity experiments were also conforming to the above discussion shown in the selective adsorption analysis. As to the selective transport through the MIMs, two diametrically opposite mechanisms36 could be concluded as facilitated permeation37 and retarded permeation.38 Detailed discussion are provided in Support Information. In this research, the second mechanism played a key role for the transport rate of Ars and artemether through the FMIMs as shown in the perm-selectivity experiments. It should be originate from imprinting procedure in the presence of Ars molecules, which leading the creation of specific rebinding cavities at the surface of FMIMs. That is to say,

11


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Ars molecules can be preferentially bond to the affinity binding cavities at the surface of FMIMs. Hence, artemether could be hardly adsorbed onto the FMIMs and transferred continuously through the FMIMs, as shown in Figure S2. Regeneration and Stability of the FMIMs. To test the regeneration and stability of FMIMs, the adsorption/desorption procedure was repeated for 5 times by the same imprinting membrane. A mixture of methanol and acetic acid (9:1, V/V) was used as eluent. The regeneration performances of FMIMs were described in Figure 9 (inset). As shown in Figure 9, the FMIMs could hold steady for five regenerated cycles with only 6.1% loss of initial adsorption capacity. The selective permeation experiments were also performed to detect the selectivity for the FMIMs after five regenerated cycles. As shown in Figure 9 and Table 3, it can be assumed that the FMIMs can be reused without decreasing its selective recognition ability and adsorption capacities significantly after five regenerated cycles. The possible reason for the decrease in adsorption and perm-selectivity performance may be that a few recognition cavities in FMIMs might be destroyed during the regenerated cycles, the deformed cavities could no more match the templates.

CONCLUSIONS In conclusion, a surface functional monomer-directing prepolymerization system was developed to prepare the molecularly imprinted composite membranes with a high density of specific recognition sites for Ars molecules. As indicated above, this prepolymerization system could not only drive the target species enriched onto the surface of RCMs, but also direct the selective imprinting copolymerization at the surface of RCMs at the same time. After the removed of template molecules by solvent extraction, the sterically complementary imprinting cavities for template molecules were formed in the FMIMs which could be used for selective rebinding of template molecules (Ars). That is to say, the as-prepared FMIMs can form a well-dispersed imprinting polymer monolayer with complementary imprinting cavities of template molecules during the imprinting procedure. It has been demonstrated that the key design of prepolymerization system could significantly improve the rebinding capacity, adsorption rate, and perm-selectivity (separation factor β is 10.06) of imprinting membrane materials. Although the research here is mainly focused on the imprinting of Ars, we hold that this facile and

12


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straightforward method is widely appropriate for a variety of organic compounds. In addition, the high separation selectivity combine with the excellent regeneration capacity recommends the developed FMIMs as a promising candidate for membrane-based Ars delivery and separation.

REFERENCES (1) Ulbricht, M. Advanced functional polymer membranes. Polymer. 2006, 47, 2217-2262. (2) Carta, M.; Maplass-Evans, R.; Croad, M.; Rogan, Y.; Jansen, J. C.; Berardo, P.; Bazzarelli, F.; McKeown, N. B. An Efficient Polymer Molecular Sieve for Membrane Gas Separations. Science 2013, 339, 303-307. (3) Gin, D. L.; Noble, R. D. Designing the Next Generation of Chemical Separation Membranes. Science. 2011, 332, 674-676. (4) van Reis, R.; Zydney, A. Membrane separations in biotechnology. Curr. Opin. Biotechnol. 2001, 12, 208-211. (5) Wulff, G. Enzyme-like Catalysis by Molecularly Imprinted Polymers. Chem. Rev. 2002, 102, 1-28. (6) Li, S. J.; Ge, Y.; Piletsky, S. A.; Turner, A. P. F. Hierachically structured hollow silica spheres for high efficiency immobilization of enzymes. Adv. Funct. Mater. 2011, 21, 3344-3349. (7) Mosbach, K.; Ramström, O. The Emerging Technique of Molecular Imprinting and Its Future Impact on Biotechnology. Nat. Biotechnol. 1996, 14, 163-170. (8) Haupt, K.; Mosbach, K. Molecularly Imprinted Polymers and Their Use in Biomimetic Sensors. Chem. Rev. 2000, 100, 2495-2504. (9) Li, H. B.; Li, Y. L.; Cheng, J. Molecularly imprinted silica nanospheres embedded CdSe quantum dots for highly selective and sensitive optosensing of pyrethroids. Chem. Mater. 2010, 22, 2451-2457. (10) Kyzas, G. Z.; Bikiaris, D. N.; Lazaridis, N. K. Selective separation of basic and reactive dyes by molecularly imprinted polymers (MIPs). Chem. Eng. J. 2009, 149, 263-272. (11) Gauczinski, J.; Liu, Z. H.; Zhang, X.; Schönhoff, M. Surface molecular imprinting in layer-by-layer films on silica particles. Langmuir 2012, 28, 4267-4273. (12) Haupt, K.; Mosbach, K. Molecularly Imprinted Polymers and Their Use in Biomimetic Sensors. Chem. Rev. 2000, 100, 2495-2504. 13


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biochemical and molecular approaches for enhanced production. Planta medica, 2003;69:289-299. (24) Ferreira, J. F.; Gonzalez, J. M. Analysis of underivatized artemisinin and related sesquiterpene lactones by high-performance liquid chromatography with ultraviolet detection. Phytochem. Analysis 2009, 20, 91-97. (25) World Health Organization. The Use of Artemisinin and its Derivatives as Antimalarial Drugs. Malaria Unit, Division of Control of Tropical Diseases. WHO, Geneva 1998. (26) Wu, Y. L.; Meng, M. J.; Liu, X. L.; Li, C. X.; Zhang, M.; Ji, Y. J.; Sun, F. Q.; He, Z. H.; Yan, Y. S. Efficient one-pot synthesis of artemisinin-imprinted membrane by direct surface-initiated AGET-ATRP. Sep. Purif. Technol. 2014, 131, 117-125. (27) Pan, J. M.; Li, L. Z.; Wu, R. R.; Dai, X. H.; Shi, W. D.; Yan, Y. S. Fabrication and Evaluation of Magnetic/Hollow Double-Shelled Imprinted Sorbents Formed by Pickering Emulsion Polymerization. Langmuir 2013, 29, 8170-8178. (28) Yang, B. J.; Cao, X. J. Synthesis of the Artemisinin-Imprinting Polymers on Silica Surface and Its Adsorption Behavior in Supercritical CO2 Fluid. AIChE 2011, 57, 3514-3521. (29) Gong, X. Y.; Cao, X. J. Preparation of molecularly imprinted polymers for artemisinin based on the surfaces of silica gel. J. Biotechnol. 2011, 153, 8-14. (30) Ho, Y. S.; McKay, G. The sorption of lead (II) on peat. WaterRes. 1999, 33, 578-584. (31) Ho, Y. S.; McKay, G. Pseudo second-order model for sorption processes. Process Biochem. 1999, 34, 451-465. (32) Wang, X. J.; Xu, Z. L.; Feng, J. L.; Bing, N. C.; Yang, Z. G. Molecularly imprinted membranes for the recognition of lovastatin acid in aqueous medium by a template analogue imprinting strategy. J. Membr. Sci. 2008, 313, 97-105. (33) Meng, M. J., Feng, Y. H.; Zhang, M.; Ji, Y. J.; Dai, J. D.; Liu, Y.; Yu, P.; Yan, Y. S. Optimization of surface imprinted layer attached poly(vinylidene fluoride) membrane for selective separation of salicylic acid from acetylsalicylic acid using central composite design. Chem. Eng. J. 2013, 231,132-145. (34) Langmuir, I. The adsorption of gases on plane surfaces of glass, mica and platinum. J. Am. Chem. Soc. 1918, 40, 1361. (35) Taki, K.; Arita, I.; Staoh, M.; Komiyama, J. Selective transport of D, L-Tryptophan through 15


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ACKNOWLEDGMENT This research was financially supported by the National Natural Science Foundation of China (Nos. 214060815, 21277063, 21107037, 21176107), National key basic research development program (973 Program, No. 2012CBB21500), and Natural Science Foundation of Jiangsu Province (BK20140580) are acknowledged.

ASSOCIATED CONTENT Supporting Information This material is available free of charge via the Internet at http://pubs.acs.org.

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Figure Captions Figure 1. Chemical structures of Ars (a) and artemether (b). Figure 2. Synthesis strategy of prepolymerization system and molecular imprinting on AM-APTES monolayer modified RCMs support. Figure 3. X-ray photoelectron spectroscopy (XPS) wide scan and norrow scan for C1s peaks for bare RCMs (a), APTES-RCMs (b), AM-APTES-RCMs (c), FMIMs (d). Figure 4. SEM images of pristine RCMs (a), APTES-RCMs (b), AM-APTES-RCMs (c), and FMIMs (d) (inset is a high-magnification SEM image). Figure 5. Kinetic curves and fitting model of Ars on the FMIMs and FNIMs. Figure 6. Equilibrium data and modeling for the adsorption of Ars onto FMIMs and FNIMs. Figure 7. Adsorption selectivity (a) and separation factors (b) of FMIMs toward different targets (the experiments were repeated in triplicate). Figure 8. Time-permeation performance of FMIMs (a) and FNIMs (b) toward Ars and artemether molecules (the experiments were repeated in triplicate). Figure 9. Permeation performance of the regenerated FMIMs after five adsorption/desorption cycles (inset is the regeneration performance of FMIMs).

Table Captions Table 1. Kinetics constants for the pseudo-first-order and pseudo-second-order rate equations. Table 2. Langmuir data for the adsorption of Ars onto FMIMs and FNIMs at 25 oC. Table 3. Time-permeation results of FMIMs, FNIMs and regenerative FMIMs for Ars and artemether molecules (the data are the mean of at least three independent experiments).

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Figure 1

Figure 2

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Figure 3

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Figure 4

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Figure 5

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Figure 6

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Figure 7

Figure 8

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Figure 9

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Table 1

Pseudo-first-order model Adsorbents

Qe,exp

Qe,cal

Pseudo-second-order model

k1

Qe,cal

k2

(mg g-1)

(g mg-1 min-1)d

R2

R2

(mg g-1)a

(mg g-1)b

(min-1)c

FMIMs

11.9190

11.0336

0.0065

0.8507

10.9843

0.0029

0.9985

FNIMs

3.5625

3.1210

0.0058

0.9731

3.5201

0.0646

0.9951

a

Qe,exp is the experimental value of Qe (mg g-1).

b

Qe,cal is the calculated value of Qe (mg g-1).

c

k1 is the rate constant of Pseudo-first-order model.

d

k2 is the rate constant of Pseudo-second-order model.

Table 2

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Adsorbents

Qe,exp (mg g-1)a

Qe,c (mg g-1)b

KL (mg -1)

R2

FMIMs

11.9027

12.1136

0.0039

0.9937

FNIMs

2.9272

2.9326

0.0020

0.9874

a

Qe,exp is the experimental value of Qe (mg g-1).

b

Qe,c is the calculated value of Qe (mg g-1) by Langmuir adsorption model.

Table 3

J×10-5

P×10-5

（mg cm-2 s-1）

(cm2 s-1)

Ars

7.2

0.48

artemether

22.8

5.09

Ars

21.5

4.05

artemether

22.1

4.54

FMIMs

Ars

8.11

0.56

(after five cycles)

artemether

22.57

4.90

Membrane

Substrate

FMIMs

βartemether/Ars

10.60

FNIMs

1.12

8.75

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Table of Contents Graphic

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Fabrication and Evaluation of Artemisinin-Imprinted Composite

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