Fabrication of Multilayered Molecularly Imprinted Membrane for

Research Article pubs.acs.org/journal/ascecg

Cite This: ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX

Fabrication of Multilayered Molecularly Imprinted Membrane for Selective Recognition and Separation of Artemisinin Yongqiang Zhang,†,‡ Xin Tan,†,‡ Xiao Liu,† Chunshan Li,† Shaojuan Zeng,† Hui Wang,*,† and Suojiang Zhang*,†

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†

Beijing Key Laboratory of Ionic Liquids Clean Process, CAS Key Laboratory of Green Process and Engineering, State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, No. 1 Beierjie, Zhongguancun, Haidian District, Beijing 100190, P.R. China ‡ Sino-Danish College, University of Chinese Academy of Sciences, Yanqihu Campus, No. 380 Huaibeizhuang, Huairou District, Beijing 101408, P.R. China S Supporting Information *

ABSTRACT: Molecularly imprinted membranes with multifunctional layers for artemisinin separation and purification were fabricated on porous chitosan membranes. The molecularly imprinted layer was fabricated through an in situ activator generated by electron transfer−atom transfer radical polymerization method by using artemisinin as the templet molecule. Properties of the prepared materials were characterized by SEM, IR, XPS, EDS, AFM, etc. Adsorption ability and dynamics, permeation capacity, and reusability have been investigated. Results indicate that this kind of molecularly imprinted membrane possesses desirable adsorption ability for artemisinin (18.89 mg/g) and permselectivity factors (β) as high as 2.15 and 2.03 toward artemether and artesunate, respectively. Mechanism of selective adsorption and permeation was unveiled by molecular simulation, which indicates that the tailor-made recognition sites on the membrane possess higher interaction force toward artemisinin than artemether or artesunate, resulting in artemisinin adsorption by the membrane and separation of this drug from its analogues. The method developed here provides an environmental friendly and sustainable technology for separation and purification of natural products. KEYWORDS: Artemisinin, Molecularly imprinted membrane, Chitosan, Permselectivity

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parasite.2,3 Now this natural drug has become a standard treatment worldwide for P. falciparum malaria and has been recommended as the most effective antimalarial drug by the World Health Organization (WHO) since this drug therapy has saved millions of lives across the globe, especially in the developing world.4 Recently, Ars has drawn continuous research attention all over the world, and a series of theories and technologies for Ars synthesis, extraction, and purification have been developed.5−8 The Ars content in the leaves is quite limited (0.1−1.2 wt %),9,10 and selective extraction of Ars is quite challengeable. Solvent extraction by treating the dried Artemisia annua L. with organic solvents is the most commonly applied technology in industry for Ars production, and petroleum ether is reported to be the most suitable solvent for Ars extraction.11 Besides, several kinds of new solvents (such as hydrofluorocarbons, monoethers, supercritical CO2, ionic liquids)12−17 and some

INTRODUCTION

Artemisinin (Ars), with the molecular structure shown in Figure 1, is a kind of natural product mainly obtained from the Chinese medicine herb Artemisia annua L., which exhibits a very fast and efficient action against malaria.1 Artemisinin is a sesquiterpene lactone, incorporating an endoperoxide group that can be activated through reacting with haem and iron(II) oxide, resulting in the generation of free radicals that in turn damage susceptible proteins, further leading to death of the

Received: September 26, 2018 Revised: November 13, 2018 Published: December 27, 2018

Figure 1. Molecular structures of artemisinin, artemether, and artesunate. © XXXX American Chemical Society

A

DOI: 10.1021/acssuschemeng.8b04908 ACS Sustainable Chem. Eng. XXXX, XXX, XXX−XXX

Research Article

ACS Sustainable Chemistry & Engineering techniques for process intensification (including ultrasonic and microwave)14,18−20 have been proposed to enhance Ars production. After extraction of Ars from the leaves, purification steps are needed to obtain Ars with high purity as wax oil with complex compositions could be coextracted from the leaves by the solvents.21 Traditionally, Ars is purified by recrystallization with methanol, column chromatography, etc. However, purification by recrystallization always needs multisteps to get Ars with high purity, and the chromatographic method is time-consuming and energy-sensitive as the packing material needs to be calcined at temperatures around 800 °C for regeneration.22,23 Under the requirement of sustainable development, it is necessary to develop an efficient technique with low energy consumption for Ars purification. Molecular imprinting is just like a lock that is only compatible with the correct key and is also similar to some biological systems, such as antibodies and antigens, enzymes and substrates, and hormones and receptors. Molecularly imprinted polymers (MIPs) can be easily fabricated by crosslinking the corresponding monomers and the template molecule (i.e., the molecule that needs to be purified) with hydrogen bonds, electrostatic forces, van der Waals forces, and hydrophobic interactions.24 After the template is washed out, many recognition sites could be left in the polymers. This kind of material provides an alternative technology for artemisinin purification. Usually, many of the templates are actually embedded into the inner of the polymerized networks and cannot be washed out, limiting the rebinding capacity and recognition site accessibility to the template molecules.25 Therefore, improving the adsorption and recognition capacities of MIPs is still challenging. Membrane separation technique (MST) is a comparatively ideal method which is widely used in many fields, such as solid−liquid extraction, drug purification, water treatment, oil refinement, and gas separation.26−31 Atom transfer radical polymerization (ATRP) is one of the most versatile and robust techniques to synthesize well-defined polymers.32 Compared with traditional polymerization process, ATRP offers some advantages, including that the initiator is anchored on the membrane surface in advance, so the polymerization process can only occur on the surface, avoiding embedding of the template molecules. In addition, the initiators at the end of the polymerization chains are still alive after being grafted so that further polymerization becomes possible.33,34 In order to obtain more recognition sites on the surface of molecularly imprinted membranes (MIMs), we proposed to utilize the ATRP method to give a MIP layer to increase the recognition sites. The common catalysts for ATRP (such as Cu(I) complex) are generally sensitive to air and moisture, which require anaerobic conditions and therefore are not suitable for sustainable processes. Reports have offered a new catalytic system for initiating ATRP by active metal catalysts, where the activator is generated by electron transfer (AGET).35−37 For instance, the active Cu(I) could be produced in situ from oxidatively stable Cu(II) via a reduction reaction by benign reducing agents such as citric acid or ascorbic acid (vitamin C) aqueous solution. A typical AGET−ATRP process is shown in Figure 2. In this work, molecularly imprinted membranes were fabricated through an AGEFT−ARTP process by employing artemisinin as the template and porous chitosan membrane with antibacterial ability as the substrate. Ag nanoparticles were decorated on the surface of MIMs to prevent materials from

Figure 2. Typical reactions of an AGET−ATRP process.

bacterial pollution and destruction. Physicochemical properties of the as-prepared MIMs were characterized by SEM, XPS, EDS, AFM, ATR-FTIR, etc. Adsorption ability and dynamics for Ars, permeation property, and kinetics of separation of Ars from its analogues were investigated in detail. Interactions between the drugs and MIMs were studied using molecular simulation to reveal the mechanism of adsorption and permeation properties of the prepared materials. This work will be helpful to understand the selective separation phenomena and improve the recognition ability of MIPs. Additionally, this kind of MIM has the potential to be applied in drug purification, chiral resolution, natural product separation, and many other related fields.

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EXPERIMENT

Materials. Chitosan powder (BR, the degree of deacetylation is 85−95%; Sinopharm Chemical Reagent, Beijing, China), dibutyl phthalate (DBP, Sinopharm Chemical Reagent, Beijing, China), dopamine hydrochloride (DPA, 98%, Aladdin), tris(hydroxymethyl)aminomethane (Tris-HCl, 99%, Aladdin), artemisinin (98%, Aladdin), artemether (Are, 98%, Aladdin), artesunate (Aru, 98%, Aladdin), tetraethyl orthosilicate (TEOS, 98%, Sinopharm Chemical Reagent, Beijing, China), ethylene glycol dimethacrylate (EGDMA, 98%, Aladdin), acrylamide (AM, 99%, Aladdin), copper(II) bromide (CuBr2, 99%, Aladdin), ascorbic acid (99%, Aladdin), hexadecane (99%, Sinopharm Chemical Reagent, Beijing, China), 2,2′-bipyridine (98%, Aladdin), 2-bromoisobutyryl bromide (2-BIBB, 99%, Aladdin), silver nitrate (AgNO3, 99%, Aladdin), and petroleum ether with a boiling point range of 30−60 °C (Sinopharm Chemical Reagent, Beijing, China) were used as received. All solvents used in the synthetic process were at least analytical grade. Membrane Synthesis. Synthesis of Porous Chitosan Membrane (PCM) and Nano-SiO2 Modified Membrane (SiO2@PCM). To prepare the porous chitosan membrane, 2.5 g of chitosan powder was dissolved in 100 mL of 2.0 wt % acetic acid solution with vigorous stirring to give a 2.5 wt % homogeneous liquid mixture. After that, 1 mL of DBP, used as the porogen, was dropped into 20 g of the above solution to achieve a milky mixture under stirring (1000 rpm, 2 h). The as-prepared mixture was cast on a glass plate using a scraper, which was then put in the dryer under 50 °C for 12 h. Upon complete drying, the membrane was neutralized with 100 mL of 2.5 wt % sodium hydroxide solution and then washed with deionized water. Then acetone was used to rinse the membrane to remove the porogen, and the formative porous chitosan membranes were finally obtained. The nano-SiO2 modified membrane (SiO2@PCM) was prepared on the as-prepared PCM through direct hydrolysis of tetraethyl orthosilicate (TEOS) according to a modified Stöber method.38 Typically, five pieces of PCM with a total mass of 2.35 g (each piece of the prepared membrane was cut into similar rectangles (around 15 × 8 mm) with scissors, with the total mass of five pieces higher than 2.35 g (based on our experience). When they were used for B


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ACS Sustainable Chemistry & Engineering experiments, the excessed amount was carefully cut to control the weight to 2.35 g) were immersed in solution A (mixture of 3.5 mL TEOS and 60 mL ethanol), and then solution B (mixture of 6.8 mL aqueous ammonia solution with a concentration of 28 wt % and 30 mL of deionized water) was quickly added to solution A containing PCM in a 250 mL flask with a stirring speed of 650 rpm, and the obtained solution was stirred for 1 h to accomplish the hydrolysis. The nano-SiO2 modified membrane was finally rinsed with ultraclean water to remove any SiO2 particles that were not adhered to the membrane. Synthesis of Polydopamine-Modified SiO2@PCM (PDA@SiO2@ PCM, PSP) and Ag Particles Composite PSP (Ag@PDA@SiO2@PCM, APSP). The typical self-polymerization and adhesion processes were used to give a bioinspired synthetic layer. Dopamine solution (4 mmol/L) was prepared by dissolving dopamine hydrochloride into Tris-HCl aqueous solution (pH = 8.5). The SiO2@PCMs were then dipped into the dopamine aqueous solution, and the reaction system was kept stirring for 12 h at room temperature. After the reaction, the polydopamine layer was directly formed on the SiO2@PCM surface, and the unreacted dopamine as well as the redundant PDA particles were washed out with deionized water. Subsequently, in order to get antibacterial membranes, a nanosliver particle layer was prepared on the PDA@SiO2@PCM. Briefly, the PDA@SiO2@PCM was first soaked with ascorbic acid aqueous solution (0.25 mmol/L) for 1 h, which was then dropped into silver nitrate aqueous solution (0.1 mol/L). The solution was then left to react for 5 min to allow assembly of Ag nanosheets on the PDA@ SiO2@PCM surface. Surfaces of the Ag-based membranes (Ag@ PDA@SiO2@PCM, APSP) were then carefully washed with deionized water to terminate the reaction, and the membranes were dried in a vacuum oven at 50 °C for 12 h. Synthesis of BIBB-Modified APSP (Br−Ag@PDA@SiO2@PCM, BAPSP) and Molecularly Imprinted Nanocomposite Membrane (MIPs@Ag@PDA@SiO2@PCM, MAPSP). For the immobilization of AGET−ATRP initiator, 2 mL of bromoisobutyryl bromide (BIBB) was slowly dropped into a 100 mL flask containing one piece of APSP and 60 mL of ethanol in an ice−water bath, and then 1.5 mL of triethylamine was added to the above mixture as the acid-binding agent to start the reaction. After 2 h, the system was taken out from the ice−water bath and allowed to react for 18 h at room temperature, and the whole process was kept under nitrogen atmosphere. The Br− Ag@PDA@SiO2@PCM (BAPSP) was finally obtained by being thoroughly washed with ethanol and then deionized water. The final step was to synthesize the molecularly imprinted polymer layer on the surface of BAPSP to get MIP@Ag@PDA@SiO2@PCM (MAPSP). First, the Cu(II) complex initiator system AGET−ATRP was prepared as follows: copper(II) bromide (0.1 mmol), 2,2′bipyridine (0.1 mmol), and hexadecane (0.2 g) were dissolved in 5.0 mL of ethanol in a flask and heated at 60 °C, and then the resulting mixture was cooled to 4 °C in a refrigerator. Five pieces of BAPSP with a total mass of 2.35 g, artemisinin (0.2 mmol), acrylamide (0.6 mmol), and ethylene glycol dimethacrylate (4.0 mmol) were put in a 100 mL flask with 40 mL of ethanol, and the mixture was sonicated for 30 min and then was left to stand for 24 h to give a stable system. After that, the Cu(II) complex initiator mentioned above was dropped into the flask, which was then degassed by nitrogen for 1 h. An ascorbic acid aqueous solution (0.012 mmol/L, 5 mL) was ejected into the system to trigger the polymerization reaction. The whole reaction process was maintained at 50 °C for 16 h under nitrogen atmosphere. The MAPSPs were finally obtained by being extracted with petroleum ether to remove the template (i.e., Ars) and any unreacted monomers in a Soxhlet extractor, followed by drying in a vacuum oven at 50 °C for 12 h. For comparison, the nonimprinted Ag@PDA@SiO2@PCMs (NAPSP) were synthesized by the same procedure with the absence of Ars. Characterizations. The morphology of the membranes was observed by scanning electron microscope (SEM, SU8000 HITACH, Japan). The roughness of the membrane surface was investigated by atomic force microscope (AFM, Bruker MultiMode 8, Germany). Attenuated total reflectance Fourier transform infrared (ATR-FTIR)

spectra for various membranes were collected on an FTIR Nicolet560 (Nicol, USA) with a Smart iTR. ZnSe was used as the crystal plate, and all spectra were recorded over the wavenumber range from 4000 to 650 cm−1. The chemical compositions of the membrane surface were obtained by X-ray photoelectron spectroscopy (XPS, Thermo Fisher Scientific ESCALAB 250Xi, USA) and energy dispersive spectroscopy (EDS, Oxford Aztec, U.K.). High-performance liquid chromatography (HPLC, Shimadzu LC-20A, Japan) was used to determine the concentrations of Ars, Are, and Aru in the left solutions in different rebinding experiments with the calibration curve of each standard sample under the wavelength of 213 nm (see Figures S1 and S2 in Supporting Information for details of chromatographic conditions and calibration curves). Rebinding Experiments. Rebinding abilities of the as-prepared membranes to absorb Ars were analyzed by a static adsorption system. For the adsorption isotherm experiments, one piece of MAPSP or NAPSP was dipped into 20 mL of Ars/ethanol solutions with different concentrations of 0.20, 0.40, 0.60, 0.80, and 1.00 mg/mL, and the membrane was immersed in the solution for 1 h under room temperature. For the adsorption kinetics studies, one piece of MAPSP or NAPSP was immersed into 20 mL of Ars/ethanol solution with a concentration of 0.4 mg/mL. The concentrations of Ars in the solutions were determined with HPLC at different time intervals of 10, 20, 30, 40, 50, 80, 100, 150, 200, and 300 min, and the binding capacities of MAPSP and NAPSP were calculated according to the formula as follows:

Bt =

(C0 − Ct )V m

(1)

Be =

(C0 − Ce)V m

(2)

where Bt (mg/g) and Be (mg/g) represent the artemisinin adsorption amount per gram of the membrane when the processes were at time t and equilibrium time, respectively; Ct and Ce are the concentrations (mg/mL) at time t and equilibrium time, respectively; C0 is the initial Ars concentration; V is the volume (mL) of the solution; and m is the mass (g) of MAPSP or NAPSP. To verify the abilities of MAPSP or NAPSP to selectively adsorb Ars, a mixture containing Ars and its structural analogues, i.e., artemether (Are) and artesunate (Aru; Figure 1), was prepared, with the initial concentration of each drug being set at 1.5 mmol/mL. Then one piece of MAPSP or NAPSP was dropped into the above solution for 3.0 h. The selectivity factor (α) was determined as

α=

BM BN

(3)

where BM and BN represent the adsorption amount per gram of MAPSP and NAPSP, respectively. Permeation Experiments. Permeation experiments were carried out to reveal the selective adsorption mechanism of MAPSP toward Ars. In this work, the analogue competitive permeation and timedependent permeation experiments were evaluated using a feeding solution consisting of Ars, Are, and Aru (concentration of each drug was 2.0 mg/mL). The whole process was performed on U-shaped device (Figure S3, Supporting Information), which consists of two Lshape tubes, with one side containing the feeding solution of Ars, Are, and Aru dissolved in ethanol and the other side containing the receiving solution with ethanol only. The two L-shaped tubes were separated by sealing device containing MAPSP in the middle. The permeation flux J (mg·cm−2·h−1), permeation coefficient P (cm2·h−1), and permselectivity factor (β) were calculated according to the following formulas: Ji = Pi = C

ΔCi·V Δt ·A

(i = Ars, Are, Aru)

Ji ·d (Cfi − Cri)

(i = Ars, Are, Aru)

(4)

(5)


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ACS Sustainable Chemistry & Engineering Scheme 1. Schematic Illustration of the Synthesis of MAPSPa

a

The last two pictures show the interaction sites on the membranes and Ars: the blue and white balls stand for the N and H atoms of amino groups on the membrane; the red balls stand for oxygen and the grey balls stand for carbon in Ars; and the dashed lines stand for the interaction forces.

Figure 3. SEM images of different membranes: (a) PCM, (b) SiO2@PCM, (c) PSP, (d) APSP, and (e) MAPSP. Bottom right: ATR-FTIR spectra of the above membranes.

βm , n =

Pi , m Pi , n

A series of molecular dynamics simulations were performed with GROMACS 5.1.1. The parameters for bonds, angles, dihedrals, and Lennard-Jones interactions for all the components were taken directly from GAFF, while the partial charges were obtained using the restrained electrostatic potential (RESP) method at the B3LYP/631+G(d,p) level of theory. Periodic boundary conditions were applied with particle mesh Ewald summation of the hydrogen bonds of the system. The equations of motion were integrated using a leapfrog integration algorithm with a time step of 2.0 fs. A cutoff radius of 1.1 nm was set for short-range van der Waals interactions and real-space hydrogen bonds. The particle mesh Ewald summation method with an interpolation order of 4 and Fourier grid spacing of 0.11 nm was employed to handle long-range hydrogen bonds in reciprocal space. The temperature and pressure were controlled by a V-rescale thermostat and Parrinello−Rahman, with update frequencies of 0.1 and 1.0 ps, respectively, to control the temperature at 30 °C and pressure at 1 atm. The simulation trajectories were recorded at an interval of 100 fs for further structural and dynamics analysis.

(i = Ars, Are, Aru; m = MAPSP; n = NAPSP) (6)

where V, A, and d represent the volume of the feeding (or receiving) solution (mL), effective membrane area (cm2), and membrane thickness (obtained by SEM), respectively; ΔCi/Δt represents the concentration changes of the receiving solution with time; and (Cfi − Cri) is the concentration difference between the feeding and receiving solutions. Molecular Simulation. The recognition sites on MAPSP were modeled by polyacrylamide rings, which were optimized to adapt to the Ars molecule.39 The fabrication process of this ring is the same as the formation of recognition sites, so this polymerized ring can be regarded as the outer recognition groups on the recognition sites, which could be further used to investigate the interactions. Restraints were applied to avoid drastic rearrangement of the ring. For NAPSP, there was no templet molecule, and restraints in the ring and intramolecular hydrogen bonds can be formed after optimization. Simulations for all the systems were started from solutions containing Ars, Are, Aru, ethanol, and polyacrylamide rings, and the initial configurations were generated by Packmol 13.112. D


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ACS Sustainable Chemistry & Engineering

Figure 4. XPS wide scans of different membranes (a) and narrow scans for Si 2p (b), Br 3d (c), Ag 3d (d), and C 1s (e) peaks.

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RESULTS AND DISCUSSION Fabrication of MAPSPs. The process of MAPSPs fabrication is illustrated in Scheme 1. Chitosan was chosen as the membrane raw material because of its wide availability, promising antimicrobial activity, biocompatibility, and bioactivity.40−42 After successful fabrication of porous chitosan membranes (PCMs) following the procedure described in the Experiment section, the nano-SiO2 modified layers were obtained by hydrolysis of TEOS to make the PCMs rougher for large surface area as indicated in AFM results shown later. Then self-polymerization of dopamine was performed to form a layer covering the surface of SiO2@PCM, and this layer can provide amino groups as the active sites for the subsequent reactions. The high adhesiveness of PDA@SiO2@PCM (PSP) and enhanced specific surface area should lead to excellent adsorption capacities of PSP. Then an in situ coating of sliver was carried out on the PDA-based layer. PDA has the ability to bind ions of Ag+, and ascorbic acid can reduce Ag+ to form metal silver,43 which offers an opportunity to decorate PDA@ SiO2@PCM with silver nanosheets. These silver-modified chitosan membranes should display a good antibacterial capacity for keeping the membranes away from bacterial pollution and destruction as indicated in literature,44−46 especially when it was exposed to moisture or wax, organic components in botanical cells after being used. This conclusion was confirmed by antimicrobial assay (Figure S4, Supporting Information), which indicated that compared with the control experiment, the one with MAPSP showed excellent antibacterial ability, implying the obvious bacterial inhibition zone. The BIBB-modified membrane (Br−Ag@PDA@SiO2@PCM) was then synthesized to make the initiators anchored on the surface, and an AGET−ARTP process was carried out to construct MIPs layer on the top. Finally, after removal of the template molecules (i.e., Ars), the MAPSPs were obtained and used for further study. The photographs of the materials obtained in each step are shown in Figure S5, Supporting Informaton. Characterizations of the Materials. Physicochemical properties of the as-prepared membranes were characterized using various techniques. The microstructures of the membranes in each step were observed by SEM. As can be seen from Figure 3, there are many microchannels distributed on the surface and inner of PCM, which can provide better swelling ability to help improve adsorption capacity of the

membrane and make the graft with other functional groups possible. Figure 3b shows the morphology of PCM modified by nano-SiO2, and it can be clearly seen that the surfaces of PCM were covered by SiO2 particles indicated by the white dots in the picture. Comparison of the ATR-FTIR spectrum of SiO2@PCM with that of PCM (Figure 3) also showed that the peak around 3300 cm−1 for the stretch of −OH and −NH2 disappeared, which indicated successful cover of the membrane with SiO2. After polydopamine was covered on the surface of SiO2@PCM, a rough layer can be seen on the surface of the membrane (Figure 3c), and the ATR-FTIR peak around 3300 cm−1 for amino group emerged, demonstrating the cover of polydopamine layer. Then after introduction of Ag onto the membrane, many silver particles can be seen from Figure 3d, which shows decoration of Ag particles on the surface of PDA@SiO2@PCM. The finally prepared membrane exhibited a comparatively rougher layer covering the surfaces of SiO2 particles and porous membrane with Ag nanosheets (Figure 3e), indicating that a molecularly imprinted polymer layer was modified on Br−Ag@PDA@SiO2@PCM. Also, in the ATRFTIR spectrum of MAPSP, the peak around 1620 cm−1 represents the bending vibrations of CC in PDA, and that at 1506 cm−1 could be attributed to the presence of N−H group in PDA as well as polyacrylamide, implying successful introduction of the designed layers to MAPSP. Furthermore, XPS wide scans and narrow scans were collected to analyze the surface chemical compositions of the various membranes prepared in each step, as shown in Figure 4. Compared with the XPS spectrum of PCM, that of SiO2@ PCM showed a signal of Si 2s peak, which indicated the formation of SiO2 layer and was further confirmed by the Si 2p narrow scan in Figure 4b. After the membrane was modified with PDA, a clear N 1s peak showed up, demonstrating the formation of assembled PDA layer. In the spectrum of APSP (i.e., Ag-modified PDA@SiO2@PCM), a Ag 3d peak appeared. Combined with the Ag 3d narrow scan, it suggested the decoration of Ag nanosheets on the surface. Meanwhile, the wide and narrow scans of Br 3d peaks of MAPSP were ascribed to the successful anchoring of Br on the surface of APSP. In addition, the curve-fitting XPS spectra of C 1s were studied in detail to further reveal the surface structure of MAPSP, as illustrated in Figure 4e. The two typical peaks of C−C and C− N corresponded to the groups in MIPs (i.e., polyacrylamide) and PDA layers, respectively. The peaks of CO, CO, O E


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ACS Sustainable Chemistry & Engineering CO, and OCO were also detected, demonstrating the successful coating of MIPs layer. Moreover, composition analysis using energy dispersive spectrum (EDS) mapping in Figure S6 (Supporting Information) also indicates the successful coatings of C, O, N, Si, Ag, and Br on the MAPSPs surface, in good accordance with the XPS results. EDS and XPS analysis obviously illustrated the formation of the bioinspired multilayer nanocomposite structure. In order to get more information on the MAPSP surface, an area of 23 μm2 of the surface was further investigated by atomic force microscope (AFM); the corresponding mapping image is shown in Figure S7, and the detailed results of each term are listed in Table S1 (Supporting Information). The results indicate that the average roughness of MAPSP reached 115 nm, which could contribute to a comparatively large specific surface area. Selective Binding and Kinetic Study. The adsorption ability of MAPSP or NAPSP was analyzed using a static adsorption system, where the membrane was immersed in an artemisinin/ethanol solution. The adsorption isotherms of MAPSP and NAPSP were established, and the Langmuir model was used to fit the data to obtain a deeper understanding of the imprinted effect. As can be seen from Figure 5, the binding amounts of MAPSP and NAPSP for Ars

Figure 6. Adsorption kinetic curves of MAPSP and NAPSP in pseudo-second order.

increasing, the adsorption amount slowly increased and did not change too much after 200 min. As a contrast, the adsorption rate and equilibrium amount of NAPSP were much lower than those of MAPSP. The fast adsorption rate of MAPSP can be ascribed to the large specific area of the nanocomposite multilayer structure of this material. Moreover, the pseudo-second-order equation was used to fit the kinetic data, and this adsorption process can be well-fitted using this model (Table S4), which indicated that the adsorption of MAPAP was a chemisorption dominating process, attributed to the strong interactions between Ars and the specific recognition sites on the surface of MAPSP. The selective adsorption capacity of MAPSP was also investigated by evaluating its ability to adsorb Ars toward its analogues. Aru and Are (Figure 1), which have similar but different molecular structures and dimensions from Ars (see Figure S9 for dimensions), were chosen as the analogues for comparison. The results in Figure 7 indicate that the asprepared MAPSP showed a much higher adsorption ability toward Ars and was comparatively insensitive to Aru or Are. The Ars selective factor (α) of MAPSP toward NAPSP reached 6.70, while those for Aru and Are were less than 1.40. Importantly, compared with other molecularly imprinted materials for Ars (Table S5), the as-prepared MAPSP

Figure 5. Fitting of Ars adsorption data using the Langmuir model.

showed an increasing trend with the increase of drug concentration. The MAPSP showed a higher rebinding ability for Ars than NAPSP, attributed to the recognition sites on the surface of MAPSP that can grasp Ars. For instance, when the initial Ars concentration was set at 1.0 mg/mL, MAPSP showed a rebinding amount of 14.85 mg/g in 1 h, which was much higher than that of NAPSP (4.42 mg/g). In addition, the Freundlich model was also used to fit the experimental data, but the degree of fitting for the Freundlich model (R2 = 0.9528) was lower than that for Langmuir model (R2 = 0.9908; Tables S2, S3 and Figure S8, Supporting Information). Therefore, the Langmuir model is considered to be more suitable to fit the data for artemisinin adsorption. The adsorption kinetics of MAPSP and NAPSP in specific time intervals were investigated to reveal the rate-determining step and adsorption mechanism of MAPSP. As can be seen from Figure 6, the adsorption rate was high within the first 60 min, when the adsorption amount can reach 12.29 mg/g (71% of the maximum value). With adsorption time further

Figure 7. Selective adsorption abilities of MAPSP and NAPSP (the bars stand for the adsorption amount of the materials, and the square points stand for the selectivity factor). F


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templet molecule as well as the relationship between selective permeation capacity and its recognition sites. The isothermal permeation study was carried out to reveal selective separation mechanism, and the results are given in Figure 9. When the concentration of Ars increased from 0.2 to

possesses comparable or higher adsorption ability for artemisinin, and it exhibited the highest imprinting factor α. The results suggested that MAPSP has an excellent selective adsorption capacity toward the target molecule Ars, whereas NAPSP has no such selective adsorption ability as indicated by the similar adsorption capabilities toward the three drugs. Therefore, there are a large number of imprinted cavities with a remarkable capacity for Ars recognition on the surface of MAPSP, but not on the NAPSP surface. The regeneration ability is also an important index to evaluate the performance of MAPSP. In this study, the asprepared MAPSP was used to adsorb Ars from ethanol solution. After detection of adsorption amount by HPLC, the material was separated from the solution and washed with petroleum ether until no Ars was detected. Afterward, it was used to adsorb Ars again. The above procedures were repeated until the adsorption−desorption cycles were carried out eight times. Results in Figure 8 show hat MAPSP exhibited excellent

Figure 9. Isothermal permeation of Ars through MAPSP and NAPSP.

1.0 mg/mL, the permeation fluxes (J values) of Ars through MAPSP and NAPSP both enhanced, but the flux through MAPSP was much lower than that for NAPSP as indicated by the relatively lower J values of MAPSP compared with NAPSP. Meanwhile, the permselectity factor βNAPSP/MAPSP increased with Ars concentration and reached a maximum of 8.23 at the concentration of 0.6 mg/mL, and then it decreased with the concentration of Ars further increasing. These results further indicated that the recognition sites on the surface of MAPSP can adsorb lots of Ars molecules, which led to a decrease of permeation flux of this drug through MAPSP. The transport fluxes and coefficients of different molecules through the membranes were studied, which could provide an important reference for the potential application of our asprepared MAPSP. The time-dependent permeation results of MAPSP and NAPSP are shown in Figures 10a and 10b, respectively. It is clear that with increasing time, the concentration of Ars in the receiving phase increased, and then it seemed to remain constant after 200 min as the recognition sites were saturated at this time and an equilibrium was reached. Because some artemisinin molecules interacted with the recognition sites on the MAPSP, artemisinin concentration in the receiving solution was lower than that of artemeter or artesunate. In contrast, the concentrations of the three analogues had no obvious difference on NAPSP because there were no such recognition sites on this kind of membrane. The permeation fluxes, permeation coefficients, and selectivity factors of the permeation experiments were also calculated and are summarized in Table 1. The permeation factors β of MAPSP were 2.03 (βAru/Ars) and 2.15 (βAre/Ars), clearly indicating the excellent imprinted effect of our asprepared MAPSP and the successful formation of the specific recognition sites toward Ars. Molecular Simulation. In order to achieve a better understanding of the selective adsorption mechanism of the membranes, we established a theoretical system for modeling MIMs, and the interaction forces and average distances between the molecules and the polymer ring were calculated. The interaction sites of Ars were first determined, which indicated that artemisinin tended to interact with the sites

Figure 8. Adsorption−desorption cycles of MAPSP for Ars adsorption.

adsorption capability in all the eight cycles, especially in the first six runs, where the ability for Ars adsorption was maintained at a high level. For instance, after being recycled and reused six times, the adsorption amount for Ars could still reach 18.13 mg/g, compared with 18.89 mg/g for the first cycle. Temperature is an important factor to affect the elution rate of artemisinin from the membrane. To explore if the artemisinin elution rate would affect the reproducibility of the materials, removal of artemisinin from the membrane was also performed at different temperatures from 40 to 60 °C. Recycling and reuse of the membranes obtained under different elution temperatures for artemisinin adsorption were performed, and the results are shown in Figure S10, which indicated that changing the temperature of Soxhlet extraction process for target compound removal had no obvious effect on reusability of the membrane. Permselectivity. On the surface of MAPSP, there are lots of specific recognition sites, which were created in the fixation of the linking groups of polyacrylamide during the AGET− ATRP process and were predetermined by the functional group position, molecular shape, and size of Ars. Selective permeation study of the molecularly imprinted membranes was further investigated to provide incisive comprehension about the selective permeation capacity of MAPSP toward the G


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indicated that Ars has stronger interactions with the recognition sites of MAPSP compared with NAPSP as indicated by the lower van der Waals interaction energy (−34.6035 vs −9.5623 kJ·mol−1), hydrogen bond interaction energy (−73.4465 vs −6.9678 kJ·mol−1), and shorter distance (0.8090 vs 1.1294 nm). The hydrogen bonds between Ars and MAPSP are stronger than van der Waals interactions. The strong interactions between Ars and MAPSP led to firm grasp toward the templet molecule, so the Ars can be stably adsorbed by MAPAP but not NAPSP as the latter has no recognition sites. Meanwhile, Ars has stronger interaction forces with the recognition sites than its analogues as implied by the lower energy (−34.6035 kJ·mol−1 (Ars) vs −13.8327 kJ·mol−1 (Are) and −35.3205 kJ·mol−1 (Aru) for van der Waals interactions; −73.4465 kJ·mol−1 (Ars) vs −10.766 kJ·mol−1 (Are) and −10.2943 kJ·mol−1 (Aru) for hydrogen bonds). The stronger interaction forces and smaller distances between Ars and MAPSP contributed to a large adsorption amount and high selective factor of MAPSP for Ars. Mechanism. Research has indicated that the template binding to recognition sites in a MIP could enable a highly selective separation.25 This phenomenon can be explained by transportation and hindrance of the template molecule (the detailed illustration can be seen in Figure S12). In the case that the transportation is driven by concentration gradient (case A), permeation is facilitated via adsorption/desorption to neighbored MIPs sites, while the nontemplet molecules are hindered by the microporous structure of the membrane. On the other hand, transportation of the template molecule could be hindered (case B) by adsorption/desorption to MIPs sites on the surface of trans-membrane pores, while the others which have no specific interactions with the membrane surface will transport through the membrane by diffusion or convection. In case A, facilitated permeation driven by preferential sorption of the template was attributed to affinity binding−slower transport of other solutes. In case B, hindered permeation was ascribed to affinity binding−faster transport of other solutes, until saturation of the MIP sites with the template is reached. In our work, the permeation results showed a slower transport rate (lower permeation value) of Ars (Figure 10a), which clearly demonstrated that the hindered permeation (case B) mechanism played the main role in selective permeation of Ars through MAPSP. The mechanism of selective adsorption for Ars is proposed and shown in Scheme 2. Ars molecules were hindered by adsorption to the recognition sites on the surface of MAPSP, and meanwhile other analogues (Are and Aru), which have no specific interaction with these recognition sites, will transport directly through the MAPSP with less barrier effect, leading to lower permeation rate of Ars through the membrane and thus separation of Ars from its analogues.

Figure 10. Time-dependent permeation of MAPSP (a) and NAPSP (b).

Table 1. Permeation Fluxes, Coefficients, and Permselectivity Factors of the Membranes for Ars, Aru, and Are at 200 min materials MAPSP

NAPSP

molecules

J (mg cm−2 h−1)

P (cm−2 h−1)

Ars Aru Are Ars Aru Are

8.92 15.70 16.10 13.99 14.26 15.33

12.47 25.39 26.89 22.43 23.78 25.55

βAru/Ars

βAre/Ars

2.03

2.15

1.06

1.14

through hydrogen bonds between the oxygen atoms of artemisinin and the amino groups of the membrane, as shown in Figure S11 and Table S6, Supporting Information. The interactions between different molecules and MIMs are shown in Table 2 and Figure 11. The simulation results

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Table 2. Interaction Forces and Average Distances of Different Molecules with MAPSP and NAPSP

materials MAPSP

NAPSP

molecules

van der Waals interactions (kJ·mol−1)

hydrogen bond interactions (kJ·mol−1)

avg distances (nm)

Ars Are Aru Ars Are Aru

−34.6035 −13.8327 −35.3205 −9.5623 −13.0037 −13.8909

−73.4465 −10.7066 −10.2943 −6.9678 −7.7770 −13.1780

0.8090 1.0956 0.9593 1.1294 1.1304 1.0433

CONCLUSIONS In this study, we have developed multilayer nanocomposite molecularly imprinted membranes through the AGET−ATRP process. Physicochemical properties of the materials were characterized by various spectroscopic techniques, which confirmed the successful preparation of the designed membranes. Study on the adsorption capability and permeation selectivity indicated that the prepared MAPSP showed excellent selective adsorption and separation performance for Ars. Due to the nanocomposite structure with comparatively H


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Figure 11. Configurations of different molecules with MAPSP and NAPSP (A: Ars and MAPSP, B: Are and MAPSP, C: Aru and MAPSP, D: Ars and NAPSP, E: Are and NAPSP, F: Aru and NAPSP).

Scheme 2. Selective Separation Mechanism of Ars through MAPSP

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large specific area, sliver decoration layer for antibacterial effect, and molecularly imprinted layer for recognition of the target molecule, both the adsorption amount and permselectivity were high, with Be reaching 18.89 mg/g and β as high as 2.15. Interactions between Ars, Aru, Are, and MAPSP were simulated to reveal the mechanism of the high adsorption capability. This kind of molecularly imprinted membranes can provide a simple, efficient, and environmentally benign process for selective separation and purification of natural products.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Xin Tan: 0000-0002-1312-4235 Hui Wang: 0000-0003-4322-6862 Notes

The authors declare no competing financial interest.

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ASSOCIATED CONTENT

ACKNOWLEDGMENTS This work was financially supported by National Key R&D Program of China (No. 2017YFB0603401-03), CAS Pioneer Hundred Talents Program, CAS/SAFEA International Partnership Program for Creative Research Teams (No. 20140491518), and the Fund of State Key Laboratory of Multiphase Complex Systems, IPE, CAS (No. MPCS-2015-A05).

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssuschemeng.8b04908. HPLC chromatograms of Ars, Aru, and Are; calibration curves, permeation apparatus, antimicrobial assay, photographs of the as-prepared materials; EDS and AFM images of MAPSP; adsorption isotherm and kinetics, molecular structures and dimensions of Ars, Are, and Aru; reusability of MAPSP obtained under different elution temperatures; comparison of different molecularly imprinted materials; molecular modeling of MAPSP; permselectivity mechanism models of MAPSP (PDF)

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REFERENCES

(1) Wright, C. W.; Linley, P. A.; Brun, R.; Wittlin, S.; Hsu, E. Ancient Chinese Methods Are Remarkably Effective for the Preparation of Artemisinin-Rich Extracts of Qing Hao with Potent Antimalarial Activity. Molecules 2010, 15 (2), 804−812. (2) Winzeler, E. A.; Manary, M. J. Drug resistance genomics of the antimalarial drug artemisinin. Genome Biol. 2014, 15 (11), 12. I


Research Article

ACS Sustainable Chemistry & Engineering (3) Cravo, P.; Napolitano, H.; Culleton, R. How genomics is contributing to the fight against artemisinin-resistant malaria parasites. Acta Trop. 2015, 148, 1−7. (4) Roll Back Malaria. World Malaria Report 2005, 2005; p 1102. (5) Kopetzki, D.; Lévesque, F.; Seeberger, P. H. A Continuous-Flow Process for the Synthesis of Artemisinin. Chem. - Eur. J. 2013, 19 (17), 5450−5456. (6) Suberu, J. O.; Yamin, P.; Leonhard, K.; Song, L. J.; Chemat, S.; Sullivan, N.; Barker, G.; Lapkin, A. A. The effect of O-methylated flayonoids and other co-metabolites on the crystallization and purification of artemisinin. J. Biotechnol. 2014, 171, 25−33. (7) Xing, H.; Su, B.; Ren, Q.; Yang, Y. Adsorption equilibria of artemisinin from supercritical carbon dioxide on silica gel. J. Supercrit. Fluids 2009, 49 (2), 189−195. (8) Tian, N.; Li, J.; Liu, S. Q.; Huang, J. A.; Li, X.; Liu, Z. H. Simultaneous isolation of artemisinin and its precursors from Artemisia annua L. by preparative RP-HPLC. Biomed. Chromatogr. 2012, 26 (6), 708−713. (9) Kumar, S.; Gupta, S. K.; Singh, P.; Bajpai, P.; Gupta, M. M.; Singh, D.; Gupta, A. K.; Ram, G.; Shasany, A. K.; Sharma, S. High yields of artemisinin by multi-harvest of Artemisia annua crops. Ind. Crops Prod. 2004, 19 (1), 77−90. (10) Nair, P.; Misra, A.; Singh, A.; Shukla, A. K.; Gupta, M. M.; Gupta, A. K.; Gupta, V.; Khanuja, S. P. S.; Shasany, A. K. Differentially Expressed Genes during Contrasting Growth Stages of Artemisia annua for Artemisinin Content. PLoS One 2013, 8 (4), e60375. (11) Lapkin, A. A.; Peters, M.; Greiner, L.; Chemat, S.; Leonhard, K.; Liauw, M. A.; Leitner, W. Screening of new solvents for artemisinin extraction process using ab initio methodology. Green Chem. 2010, 12 (2), 241−251. (12) Suberu, J.; Yamin, P.; Cornell, R.; Sam, A.; Lapkin, A. Feasibility of Using 2,3,3,3-Tetrafluoropropene (R1234yf) as a Solvent for Solid-Liquid Extraction of Biopharmaceuticals. ACS Sustainable Chem. Eng. 2016, 4 (5), 2559−2568. (13) Kohler, M.; Haerdi, W.; Christen, P.; Veuthey, J. L. Extraction of artemisinin and artemisinic acid from Artemisia annua L. using supercritical carbon dioxide. J. Chromatogr. A 1997, 785 (1−2), 353− 360. (14) Zhang, Y.; Prawang, P.; Li, C.; Meng, X.; Zhao, Y.; Wang, H.; Zhang, S. Ultrasonic assisted extraction of artemisinin from Artemisia Annua L. using monoether-based solvents. Green Chem. 2018, 20 (3), 713−723. (15) Extraction of Artemisinin Using Ionic Liquids; Bioniqs. Ltd: York, U.K., 2006. (16) Xia, Y.; Zeng, J.; Zhao, B. Extraction of Artemisinin from Artemisia annual L. with 1-Ethyl-3-methylimidazolium Bromide Enhanced by Ultrasonic Wave. Chin. J. Process Eng. 2008, 8 (4), 774−778. (17) Zhang, S.; He, H.; Huo, F.; Lu, Y.; Zhang, X.; Dong, K.; Wang, Y. A new era of precise liquid regulation: Quasi-liquid. Green Energy & Environ. 2017, 2 (4), 329−330. (18) Zhang, H.; Zhang, L.; Hu, X.; Zhou, Y.; Ding, C.; Yang, R.; Wang, X.; Li, D. Optimization of Ultrasound-Assisted Extraction of Artemisinin from Artemisia annua L. by Response Surface Methodology. Sep. Sci. Technol. 2014, 49 (5), 673−681. (19) Hao, J.; Han, W.; Huang, S.; Xue, B.; Deng, X. Microwaveassisted extraction of artemisinin from Artemisia annua L. Sep. Purif. Technol. 2002, 28 (3), 191−196. (20) Bilia, A.; Gabriele, C.; Bergonzi, M.; Melillo de Malgalhaes, P.; Vincieri, F. Variation in artemisinin and flavonoid content in different extracts of Artemisia annua L. Nat. Prod. Commun. 2006, 1 (12), 1111−1115. (21) Liu, N.; Schuehly, W.; von Freyhold, M.; van der Kooy, F. A novel purification method of artemisinin from Artemisia annua. Ind. Crops Prod. 2011, 34 (1), 1084−1088. (22) Malwade, C. R.; Buchholz, H.; Rong, B. G.; Qu, H. Y.; Christensen, L. P.; Lorenz, H.; Seidel-Morgenstern, A. Crystallization

of Artemisinin from Chromatography Fractions of Artemisia annua Extract. Org. Process Res. Dev. 2016, 20 (3), 646−652. (23) Qu, H.; Christensen, K.; Frette, X.; Tian; Rantanen, J.; Christensen, L. Chromatography-Crystallization Hybrid Process for Artemisinin Purification from Artemisia annua. Chem. Eng. Technol. 2010, 33 (5), 791−796. (24) He, C.; Long, Y.; Pan, J.; Li, K.; Liu, F. A method for coating colloidal particles with molecularly imprinted silica films. J. Mater. Chem. 2008, 18 (24), 2849−2854. (25) Ulbricht, M. Membrane separations using molecularly imprinted polymers. J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. 2004, 804 (1), 113−125. (26) Boyadzhiev, L.; Dimitrov, K.; Metcheva, D. Integration of solvent extraction and liquid membrane separation: An efficient tool for recovery of bio-active substances from botanicals. Chem. Eng. Sci. 2006, 61 (12), 4126−4128. (27) Wen, E.; Cinelli, L. D.; Murray, D.; Lander, R. J.; Sagar, S. L.; Lee, A. L. Purification of a polysaccharide conjugate vaccine using microfiltration membranes in back-ulsing mode. J. Membr. Sci. 2005, 258 (1−2), 23−34. (28) Gu, J.; Gu, H.; Zhang, Q.; Zhao, Y.; Li, N.; Xiong, J. Sandwichstructured composite fibrous membranes with tunable porous structure for waterproof, breathable, and oil-water separation applications. J. Colloid Interface Sci. 2018, 514, 386−395. (29) Marcelo, G.; Ferreira, I. C.; Viveiros, R.; Casimiro, T. Development of itaconic acid-based molecular imprinted polymers using supercritical fluid technology for pH-triggered drug delivery. Int. J. Pharm. 2018, 542 (1−2), 125−131. (30) Liu, J.; Wang, N.; Yu, L.-J.; Karton, A.; Li, W.; Zhang, W.; Guo, F.; Hou, L.; Cheng, Q.; Jiang, L.; Weitz, D. A.; Zhao, Y. Bioinspired graphene membrane with temperature tunable channels for water gating and molecular separation. Nat. Commun. 2017, 8. DOI: 10.1038/s41467-017-02198-5. (31) Yang, J.; Gong, D.; Li, G.; Zeng, G.; Wang, Q.; Zhang, Y.; Liu, G.; Wu, P.; Vovk, E.; Peng, Z.; Zhou, X.; Yang, Y.; Liu, Z.; Sun, Y. Self-Assembly of Thiourea-Crosslinked Graphene Oxide Framework Membranes toward Separation of Small Molecules. Adv. Mater. 2018, 30, 1705775. (32) Matyjaszewski, K.; Xia, J. H. Atom transfer radical polymerization. Chem. Rev. 2001, 101 (9), 2921−2990. (33) Li, C.; Wang, W.; Xu, F.; Zhang, L.; Yang, W. Preparation of pH-sensitive membranes via dopamine-initiated atom transfer radical polymerization. J. Membr. Sci. 2011, 367 (1−2), 7−13. (34) Matyjaszewski, K.; Ziegler, M. J.; Arehart, S. V.; Greszta, D.; Pakula, T. Gradient copolymers by atom transfer radical copolymerization. J. Phys. Org. Chem. 2000, 13 (12), 775−786. (35) Min, K.; Gao, H.; Matyjaszewski, K. Preparation of homopolymers and block copolymers in miniemulsion by ATRP using activators generated by electron transfer (AGET). J. Am. Chem. Soc. 2005, 127 (11), 3825−3830. (36) Wang, Y.; Li, X.; Du, F.; Yu, H.; Jin, B.; Bai, R. Use of alcohols as reducing agents for synthesis of well-defined polymers by AGETATRP. Chem. Commun. 2012, 48 (22), 2800−2802. (37) Zhang, L.; Cheng, Z.; Shi, S.; Li, Q.; Zhu, X. AGET ATRP of methyl methacrylate catalyzed by FeCl3/iminodiacetic acid in the presence of air. Polymer 2008, 49 (13−14), 3054−3059. (38) Stö ber, W.; Fink, A.; Bohn, E. Controlled Growth of Monodisperse Silica Spheres in Micron Size Range. J. Colloid Interface Sci. 1968, 26 (1), 62. (39) Zink, S.; Moura, F.; Autreto, P.; Galvão, D.; Mizaikoff, B. Virtually imprinted polymers (VIPs): understanding molecularly templated materials via molecular dynamics simulations. Phys. Chem. Chem. Phys. 2018, 20, 13145. (40) Kononova, S. V.; Kruchinina, E. V.; Petrova, V. A.; Baklagina, Y. G.; Romashkova, K. A.; Orekhov, A. S.; Klechkovskaya, V. V.; Skorik, Y. A. Two-Ply Composite Membranes with Separation Layers from Chitosan and Sulfoethylcellulose on a Microporous Support Based on Poly(diphenylsulfone-N-phenylphthalimide). Molecules 2017, 22 (12), 2227. J


Research Article

ACS Sustainable Chemistry & Engineering (41) Cruz-Romero, M. C.; Murphy, T.; Morris, M.; Cummins, E.; Kerry, J. P. Antimicrobial activity of chitosan, organic acids and nanosized solubilisates for potential use in smart antimicrobially-active packaging for potential food applications. Food Control 2013, 34 (2), 393−397. (42) Choi, C.; Nam, J. P.; Nah, J. W. Application of chitosan and chitosan derivatives as biomaterials. J. Ind. Eng. Chem. 2016, 33, 1−10. (43) Song, Y.; Jiang, H.; Wang, B.; Kong, Y.; Chen, J. SilverIncorporated Mussel-Inspired Polydopamine Coatings on Mesoporous Silica as an Efficient Nanocatalyst and Antimicrobial Agent. ACS Appl. Mater. Interfaces 2018, 10 (2), 1792−1801. (44) Chen, K.; Ray, D.; Peng, Y.; Hsu, Y. Preparation of Cu-Ag coreshell particles with their anti-oxidation and antibacterial properties. Curr. Appl. Phys. 2013, 13 (7), 1496−1501. (45) Li, M.; Huang, L.; Wang, X.; Song, Z.; Zhao, W.; Wang, Y.; Liu, J. Direct generation of Ag nanoclusters on reduced graphene oxide nanosheets for efficient catalysis, antibacteria and photothermal anticancer applications. J. Colloid Interface Sci. 2018, 529, 444−451. (46) Wu, Y.; Yan, M.; Cui, J.; Yan, Y.; Li, C. A Multiple-Functional Ag/SiO2/Organic Based Biomimetic Nanocomposite Membrane for High-Stability Protein Recognition and Cell Adhesion/Detachment. Adv. Funct. Mater. 2015, 25 (36), 5823−5832.

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Fabrication of Multilayered Molecularly Imprinted Membrane for

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