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Molecularly imprinted nanofiber membranes from cellulose acetate aimed for chiral separation
Journal of Membrane Science 357 (2010) 90–97
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Molecularly imprinted nanofiber membranes from cellulose acetate aimed for chiral separation Yuuki Sueyoshi, Chiho Fukushima, Masakazu Yoshikawa ∗ Department of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Kyoyo 606-8585, Japan
a r t i c l e
i n f o
Article history: Received 11 March 2010 Received in revised form 31 March 2010 Accepted 2 April 2010 Available online 10 April 2010 Keywords: Adsorption isotherm Chiral separation Membrane Molecularly imprinted membrane Molecular imprinting Molecular recognition Optical resolution Permselectivity
a b s t r a c t Permselectivity and throughput (flux) are important specificity in membrane separation. It is an ultimate dream for membranologists to simultaneously enhance not only permselectivity but also flux, which generally show a trade-off relationship. A breakthrough in membrane separation would be realized by adopting membranes with higher surface area, which leads to higher molecular recognition site concentration, and higher porosity. Such separation membranes would be obtained by applying an electrospray deposition technique. To this end, in the present paper, molecularly imprinted nanofiber membranes were prepared from cellulose acetate (CA) and a print molecule, a derivative of optically pure glutamic acid, such as N-␣-benzyloxycarbonyl-d-glutamic acid (Z-d-Glu) or N-␣-benzyloxycarbonyl-lglutamic acid (Z-l-Glu). Membrane performance of molecularly imprinted nanofiber membranes and usual molecularly imprinted membranes was compared in terms of adsorption selectivity, affinity constant, permselectivity, and flux. The results obtained in the present study revealed that electrospray deposition would be one of plausible methods to construct separation membranes to simultaneously enhance permselevtivity and flux. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Membrane separation, which can be operated continuously under mild conditions, is regarded as an ultimate energy-saving separation technology [1]. Its selectivity and efficiency (flux) are greatly dependent on a couple of factors [1–3]. One is solubility or partition; the term of solubility is applicable to the case of a dense membrane and that of partition to the case of a porous membrane. In other words, the term of solubility or partition means a kind of affinity between a membrane and a target substrate to be separated. The other is diffusivity of the given substrate in the membrane, in other words, migration of the target substrate from upstream side to the downstream side in the membrane. The diffusivity is mainly governed by dimension and/or shape of the given substrate. From this, the range of diffusivity is thought to be intrinsically limited. Contrary to diffusivity, affinity between the membrane and the substrate, which is so-called molecular recognition, is theoretically ranges from naught to infinity, depending on the chemical nature of the given substrate, and the combination of a target molecule and a membrane material. The introduction of molecular recognition site into a membrane is indispensable so that its permselectivity toward a target molecule can be improved.
∗ Corresponding author. Tel.: +81 75 724 7816; fax: +81 75 724 7800. E-mail address: [email protected] (M. Yoshikawa). 0376-7388/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.memsci.2010.04.005
Among plausible methods, molecular imprinting is a facile way to introduce molecular recognition sites into polymeric materials and membranes. The first application of molecular imprinting to membrane preparation was reported by Michaels and his coworkers in 1962 [4]. In the pioneering study [4], pervaporation membranes for the separation of xylene isomers were prepared from polyethylene, adopting xylene isomer (o-, m-, or p-xylene) as a print molecule. In the last part of the paper, they described that the application of molecular imprinting was not restricted to pervaporation membrane preparation and similar membrane formation process was applicable in other membrane separation area, such as gas or vapor separation and dialysis. Contrary to conventional molecular imprinting, which was studied in the preparation of molecularly imprinted silicas in the early days [5,6] and polymeric materials with specific binding sites toward a given target molecule since 1972 [7,8], Michales’ paper showed possibility that polymeric materials were directly converted into membranes having molecular recognition sites, even though starting raw materials had no specific binding sites toward target substrates. The authors’ research group extended Michales’ study to any polymeric materials, which can construct given structures and retain their forms, such as synthetic polymers [9], oligopeptide derivatives [10], derivative of natural polymers [11], and natural polymers [12]. Those polymeric materials were directly converted into materials or membranes with molecular recognition sites toward the print molecule or the print molecule analogue. Such
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method was named an alternative molecular imprinting [13,14]. The usefulness and potential of the facile method, an alternative molecular imprinting, converting polymeric materials having no specific binding sites into molecular recognition materials has been recognized by researchers and the method has been adopted for the preparation of membranes and other materials with molecular recognition sites [15–22]. As described above, an alternative molecular imprinting is a facile way to obtain membrane with specific binding sites toward a targeted substrate. However neither flux nor permselectivity of those membranes were enough for industrial applications. The enhancement of flux, in other words, throughput was especially indispensable. Molecularly imprinted membranes with a higher surface area and higher porosity are required to give both higher flux and permselectivity. Electrospray deposition is a suitable or the best method to obtain molecularly imprinted membranes with a large surface area. Electrospray deposition is expected to provide membranes consisting of polymeric nanofibers with diameters ranging from a few nanometers to several micrometers through the action of external electric field imposed on a polymeric solution or melt [23–30]. Electrosprayed nanofiber membranes with molecular recognition sites were first studied by applying an alternative molecular imprinting [31], and the mixture of polyallylamine and poly(ethylene terephthalate) was converted into molecular recognition materials to recognize 2,4-dichlorophenoxyacetic acid. Molecularly imprinted nanoparticles were also converted into electrosprayed nanofiber membranes with poly(ethylene terephthalate) [32,33]. Possibility of the enhancement of flux without the depression of permselectivity was proved by molecularly imprinted nanofiber membranes, which were fabricated from carboxylated polysulfone and N-␣-benzyloxycarbonyl-d-glutamic acid (Z-d-Glu) or N-␣-benzyloxycarbonyl-l-glutamic acid (Z-l-Glu) as a print molecule [34]. In membrane separation, flux values and permselectivies often showed a trade-off relationship. It is thought to be hard or impossible to simultaneously increase both flux value and permselectivity. Such a trade-off relationship in membrane separation is an indispensable task to be solved or is thought to be an eternal unsolved problem. However, the previous study [34] revealed that the molecularly imprinted nanofiber membranes have potential to simultaneously enhance a couple of important membrane performance, such as permselectivities and flux values. The form of molecularly imprinted nanofiber membrane is expected to simultaneously give higher flux value and permselectivity. In the present study, a derivative of natural polymer, cellulose acetate, was adopted as a candidate material for molecularly imprinted nanofiber membranes, and their membrane performance was compared with that of usual molecularly imprinted membrane previously reported [11] in terms of adsorption selectivity, affinity constant between a target molecule and molecular recognition site in the membrane, permselectivity, and flux through the membrane. 2. Experimental
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method [35]. Water purified with an ultrapure water system (Simpli Lab, Millipore S.A., Molsheim, France) was used. 2.2. Preparation of molecularly imprinted nanofiber membranes In the present study, the molecular imprinting ratio, which was the mole ratio of print molecule to constitutional repeating unit of cellulose acetate in the membrane preparation process, was fixed to be 0.50 so that the results obtained in the present study can be compared with the previous results [11]. DMF was adopted as a solvent and the polymer concentration was fixed at 30.0 wt.% in the present study. Esprayer ES-2000 (Fuence Co. Ltd., Wako, Japan) was adopted as the electrospray deposition device. Polymer solution containing either one of the print molecules was elctrosprayed at ambient temperature using an applied voltage of 30.0 kV. The syringe used in the present study had a capillary tip of 0.52 mm diameter. The feeding rate was fixed to be 1.0 mm3 min−1 . A grounded aluminum foil used as a counter electrode was placed 10 cm from the tip of the capillary. The thickness of the electrosprayed molecularly imprinted membrane with Z-d-Glu was determined to be 120 m, while that with Z-l-Glu to be 300 m. The print molecule was removed from the resultant nanofiber membranes by methanol until the print molecule could be hardly detected in methanol by UV analysis. The preparation of control nanofiber membrane was prepared from 40.0 wt.% DMF solution at the feeding rate of 0.50 mm3 min−1 . Other electrospray deposition conditions were same as those for the preparation of molecularly imprinted nanofiber membranes. The thickness of electrosprayed control membrane was determined to be 90 m. The morphology, diameter, and thickness of the electrosprayed molecularly imprinted nanofiber membranes were determined with a Hitachi S-3000 scanning electron microscope (SEM). A small section of the membrane was placed on the SEM sample holder. 2.3. Adsorption selectivity The membrane samples were immersed in a racemic Glu solution, which was the same racemic mixture studied in the membrane transport (i.e., a 50 vol. % aqueous ethanol solution of racemic Glu, with concentrations of 2.50 × 10−4 , 5.00 × 10−4 , or 1.00 × 10−3 mol dm−3 ) and the mixture was allowed to be equilibrated at 40 ◦ C. Quantitative measurements of aliquots of the solution at the initial stage and after equilibrium had been reached were made using HPLC employing a Chiralpak MA(+) column (50 mm × 4.6 mm (i.d.)) (Daicel Chemical Ind. Ltd.). The amount of Glu in the supernatant subtracted from the amount initially in the solution gave the amount of Glu adsorbed in the membrane. The adsorption selectivity SA(i/j) is defined as
SA(i/j) =
(i-Glu)/(j-Glu) [i-Glu]/[j-Glu]
(1)
where (i-Glu) and [i-Glu] are the amount of i-Glu adsorbed in the membrane and concentration in the solution after equilibrium had been reached, respectively.
2.1. Materials 2.4. Adsorption isotherms of d-Glu and l-Glu Cellulose acetate (CA), of which acetyl content was 40%, was purchased from Wako Pure Chemical Industries, Ltd. and used without purification. N-␣-Benzyloxycarbonyl-d-glutamic acid (Z-d-Glu) or N-␣-benzyloxycarbonyl-l-glutamic acid (Z-l-Glu), purchased from Watanabe Chemical Industries, Ltd. (Hiroshima, Japan), was used as a print molecule without further purification. d-Glutamic acid (dGlu), l-glutamic acid (l-Glu), sodium azide, copper sulfate, ethanol were obtained from commercial sources and used as received. N,N-Dimethylformamide (DMF) was purified by the conventional
The membrane samples were immersed in various concentrations of pure d-Glu or l-Glu solution and allowed to equilibrate at 40 ◦ C. The quantitative analyses were done as described above. The concentration of Glu in the membrane [i-Glu]M or [j-Glu]M (i = D, j = L or i = L, j = D) was determined adopting the amount of Glu adsorbed in the membrane and the volume of membrane phase, including that of membrane and that of the solution in the membrane.
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2.5. Enantioselective membrane transport A membrane with an area of 3.0 cm2 was tightly secured with Parafilm between two chambers of a permeation cell. The volume of each chamber was 40.0 cm3 . A racemic Glu solution was placed in the left-hand side chamber (L-side) and aqueous ethanol solution in the right-hand side (R-side). Each concentration of racemic Glu was 2.50 × 10−4 , 5.00 × 10−4 , or 1.00 × 10−3 mol dm−3 . Permeation experiments were carried out at 40 ◦ C with stirring. An aliquot was drawn from the permeate side at each sampling time. The amounts of d- and l-Glu transported through the membrane were determined by HPLC as described above. The flux, J (mol cm cm−2 h−1 ), is defined as J=
Qı At
(2)
where Q [mol] is the amount of transported Glu, ı [cm] the membrane thickness, A [cm2 ] the effective membrane area, and t [h] means the time. The permselectivity ˛i/j is defined as the flux ratio, Ji /Jj , divided by the concentration ratio [i-Glu]/[j-Glu] ˛i/j =
(Ji /Jj ) ([i-Glu]/[j-Glu])
(3)
3. Results and discussion 3.1. Morphology of molecularly imprinted nanofiber membranes The SEM photographs of the electrosprayed nanofiber membranes and the control nanofiber membrane are shown in Fig. 1. The nanofiber membrane shown in Fig. 1(a) was electrosprayed in the presence of Z-d-Glu as a print molecule. That shown in Fig. 1(b) was fabricated adopting Z-l-Glu as a print molecule. Fig. 1(c) shows the SEM image of the control nanofiber membrane, which was electrosprayed without a print molecule. As reported, the morphology and the diameter of the electrosprayed nanofiber membranes would be widely controlled [26–28]. A strict optimization of electrospray condition has not been conducted in the present study. The diameters of molecularly imprinted nanofiber membranes were determined to be 200–500 nm and that of the control membrane to be 300–800 nm. 3.2. Adsorption selectivity of racemic Glu The dependence of adsorption of racemic Glu on substrate concentrations is summarized in Fig. 2. The results for Z-d-Glu imprinted nanofiber membrane is shown in Fig. 2(a) and those for Z-l-Glu imprinted one in Fig. 2(e), respectively. That for the control nanofiber membrane is shown in Fig. 2(c). In Fig. 2(a), (c), and (e), each amount of Glu adsorbed by the membrane is given as a relative value (relative to that of the constitutional repeating unit of CA). Two types of molecularly imprinted nanofiber membrane showed adsorption selectivity, in other words, chiral recognition ability, while the control nanofiber membrane hardly showed adsorption selectivity. The nanofiber membrane imprinted by Z-d-Glu recognized the d-isomer in preference to the corresponding l-isomer and vice versa, as observed in molecularly imprinted CA membranes [11]. The dependence of adsorption selectivity on the substrate concentration is shown in Fig. 2(b) and (f). The adsorption selectivities for both nanofiber membranes (SA(i/j) ) increased with the decrease in the substrate concentrations from 1.00 × 10−3 mol dm−3 to 2.50 × 10−4 mol dm−3 , implying that there can be found molecular recognition sites, which were constructed by the presence of the print molecule, Z-d-Glu or Z-l-Glu, during the electrospray deposition process, in the electrosprayed
Fig. 1. SEM images of surface of Z-d-Glu imprinted nanofiber membrane (a), Z-l-Glu imprinted nanofiber membrane (b), and control nanofiber membrane (c).
nanofiber membranes. Contrary to this, the adsorption selectivity for the control nanofiber membrane was hardly dependent on the substrate concentration as shown in Fig. 2(d). 3.3. Adsorption isotherms of d-Glu and l-Glu Parameters for adsorption of Glu in the molecularly imprinted nanofiber membranes could be determined by using the experimental data obtained in the adsorption selectivity study summarized in Fig. 2. Because the molecular recognition site, which was formed by the presence of the print molecule, incorporated the isomer, of which absolute configuration was same as that of the print molecule. Contrary to this, the antipode was not adsorbed in the formed molecular recognition site. Non-specific adsorption of each enantiomer of Glu, which was an adsorption without any specific interaction, was occurred without the interference of nonspecific adsorption of antipode. In the present study, adsorption isotherms of pure d-Glu and pure l-Glu in molecularly imprinted nanofiber membranes were investigated since the authors judged that parameters for adsorption determined by using adsorption isotherms were more exact than those by using the adsorption selectivity data. The adsorption isotherms for the molecularly imprinted nanofiber membranes are shown in Fig. 3. The adsorption isotherm
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Fig. 2. Effect of the substrate concentrations on Glu adsorption (a, c, and e) and adsorption selectivity (b, d, and f) for Z-d-Glu imprinted membrane (a and b), control one (c and d), and Z-l-Glu imprinted one (e and f). (The two data of Glu adsorption in (c) are superimposed and not distinguishable.).
for l-Glu in Fig. 3(a) and that for d-Glu in Fig. 3(b) are straight lines passing through the origin, implying that the l-isomer in the disomer-selective adsorption nanofiber membrane (Fig. 3(a)) and the d-isomer in the l-isomer-selective adsorption one (Fig. 3(b)) were adsorbed without any specific interaction with the membrane. This can be anticipated from the results that the Z-d-Glu imprinted nanofiber membrane showed d-isomer adsorption selectivity, while the Z-l-Glu imprinted one recognized the lisomer in preference to the corresponding d-Glu as shown in Fig. 2. The isotherm of Glu adsorbed non-specifically in the nanofiber membrane can be represented by the following equation: [j-Glu]M = kA [j-Glu]
(4)
where j means the enantiomer of Glu adsorbed non-specifically in the nanofiber membrane, [j-Glu]M is the concentration of j-isomer of Glu adsorbed non-specifically in the membrane, kA denotes the adsorption constant, and [j-Glu] is the concentration for j-isomer of Glu in the solution equilibrated with the nanofiber membrane. On the other hand, the adsorption isotherm of d-Glu in Fig. 3(a) and that of l-Glu in Fig. 3(b) gave complicated profiles. Those target molecules were preferentially incorporated into each nanofiber
membrane. The straight lines over the substrate concentration of 5.0 × 10−4 mol dm−3 are almost parallel to those of enantiomers non-specifically adsorbed in each membrane. And the extension of those straight lines does not pass through the origin, and has positive intercept. Those adsorption isotherms exhibit dual adsorption isotherms, which consist of non-specific adsorption and adsorption on specific recognition sites toward d-isomer (Fig. 3(a)) or l-isomer (Fig. 3(b)). The isotherm of Glu adsorbed specifically in the membrane can be represented by the following equation: [i-Glu]M = kA [i-Glu] +
KS [Site]0 [i-Glu] 1 + KS [i-Glu]
(5)
where [i-Glu]M means the concentration of i-isomer of Glu adsorbed preferentially in the molecularly imprinted nanofiber membrane, KS is the affinity constant between the i-isomer and the molecular (chiral) recognition site, [Site]0 is the concentration of molecular recognition site in the membrane, and [i-Glu] denotes the concentration of i-isomer of Glu in the solution equilibrated with the nanofiber membrane. Two parameters in those adsorption equations (Eqs. (4) and (5)), which were determined
Fig. 3. Adsorption isotherms of d-Glu and l-Glu in the nanofiber membrane imprinted by Z-d-Glu (a) and the nanofiber membrane imprinted by Z-l-Glu (b). The mole ratio of print molecule to CA in the electrospray deposition process was fixed to be 0.50: kA = 1.5 × 10; [Site]0 = 7.0 × 10−3 mol dm−3 ; KS = 1.6 × 104 mol−1 dm3 for (a) and kA = 1.8 × 10; [Site]0 = 8.0 × 10−3 mol dm−3 ; KS = 1.7 × 104 mol−1 dm3 for (b).
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Y. Sueyoshi et al. / Journal of Membrane Science 357 (2010) 90–97 Table 1 Parameters for adsorption isotherms. Z-d-Glu imprinted mem. a
KA [Site]0 /mol dm−3 Ks /(mol−1 dm3 ) a b
Z-l-Glu imprinted mem. b
MIPM
MINFM
MIPMa
MINFMb
1.9 × 103 3.4 3.1 × 103
1.5 × 10 7.0 × 10−3 1.6 × 104
2.0 × 103 3.4 3.1 × 103
1.8 × 10 8.0 × 10−3 1.7 × 104
Molecularly imprinted membrane; the data were cited from the previous results [11]. Molecularly imprinted nanofiber membrane.
Fig. 4. Tentative scheme of electrospray deposition in the present study, where CA and Z-Glu (print molecule) were simultaneously electrosprayed.
to fit each adsorption isotherm in Fig. 3 best, are summarized in Table 1 together with those for previous molecularly imprinted membranes [11]. The concentration of molecular recognition sites, which were constructed by the presence of the print molecule during the electrospray deposition process, for Z-d-Glu imprinted nanofiber membrane was determined to be 7.0 × 10−3 mol dm−3 and that
for Z-l-Glu imprinted one to be 8.0 × 10−3 mol dm −3 , respectively. On the other hand, the concentrations of the previous molecularly imprinted CA membranes were determined to be ca. 3.4 mol dm−3 [11]. Against our expectation, the amounts of molecular recognition site in the molecularly imprinted nanofiber membranes were lower than that for the previous molecularly imprinted CA membrane, even though the surface area of the present nanofiber membrane was higher than that for the previous dense membrane. This can lead to the conclusion that the amount of Z-d-Glu or Z-l-Glu, which worked as a print molecule in electrospray deposition process, was less than that in the previous study [11]. This can be explained as follows: as shown in Fig. 4, in the electrospray deposition process of CA and Z-d-Glu or Z-l-Glu, most print molecule Z-Glu was solely sprayed toward the counter electrode of grounded aluminum foil accompanying with no CA molecule. As a result, small amount of the print molecule was electrosprayed together with CA molecule toward the collector. In other words, the molecular imprinting ratio, which is defined as the mole ratio of the print molecule to the constitutional repeating unit of CA, for the preparation of the molecularly imprinted nanofiber membrane was lower than that for the previous molecularly imprinted membrane. The above speculation can be supported by the affinity constants for two types of molecularly imprinted membrane, such as a molecularly imprinted nanofiber membrane and a usual molecularly imprinted membrane. The affinity constant KS for the present nanofiber membranes were determined to be 1.6 × 104 mol−1 dm3 for Z-d-Glu imprinted nanofiber membrane and 1.7 × 104 mol−1 dm3 for Z-l-Glu imprinted one, respectively. Those for the previous molecularly imprinted CA membranes were determined to be 3.1 × 103 mol−1 dm3 [11], which were less than
Fig. 5. Schematic image of the relationship between molecular imprinting ratio and interaction mode (affinity constant).
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Fig. 6. Time-transport curves of racemic Glu through the molecularly imprinted and control nanofiber membranes. (The molecular imprinting ratio, (Z-Glu)/(CA), was fixed to be 0.50; [d-Glu]L,0 = [l-Glu]L,0 = 2.50 × 10−4 mol dm−3 .)
20% of those for the present molecularly imprinted nanofiber membranes. As schematically shown in Fig. 5, the affinity constant for the molecular recognition site constructed by the print molecule and the target molecule would depend on the molecular imprinting condition (molecular imprinting ratio) and KS was increased with the decrease in the imprinting ratio (Z-Glu)/(CA) [39]. At the low molecular imprinting ratio, more functional groups interacted with one print molecule, resulting in a higher affinity constant. As a result, the affinity constant gave higher values with the decrease in the molecular imprinting ratio. This means that the amount of the print molecule effectively worked during the electrospray deposition was lower than that during previous molecular imprinting process. 3.4. Enantioselective transport of racemic Glu From the results of enantioselective adsorption studied in the previous section, those two types of molecularly imprinted nanofiber membrane were expected to show enantioselective transport ability. To this end, enantioselective transport of racemic Glu through the two types of molecularly imprinted nanofiber membrane and the control nanofiber membrane were investigated. As examples of time-transport curves for those membranes, those for the initial feed concentration of 2.50 × 10−4 mol dm−3 are shown in Fig. 6. As expected from previous results [11] and adsorp-
tion phenomena shown in Figs. 2 and 3, d-Glu was transported through the Z-d-Glu molecularly imprinted nanofiber membrane in preference to the corresponding l-isomer of Glu and vice versa. The permselectivity toward the d-Glu for the Z-d-Glu molecularly imprinted nanofiber membrane was determined to be 1.45, while that for Z-l-Glu molecularly imprinted one to be 1.44. Contrary to this, the control nanofiber membrane, which was electrosprayed without a print molecule, hardly showed permselectivity toward racemic Glu mixture. The dependence of permselectivity on the initial concentration in the feed side will give the insight into the transport mechanism; in other words, the permselectivity would be expected to increase with the decrease in feed concentration in the case that the molecular recognition sites in the nanofiber membrane, which were constructed during electrospraying process, contributed as specific recognition sites in the membrane transport. Fig. 7 shows relationship between permselectivity and flux dependence on feed concentration. As can be seen in the figure, permselectivity of molecularly imprinted nanofiber membranes was increased with the decrease in feed concentration, implying that the molecular recognition sites in the molecularly imprinted nanofiber membrane contributed to enantioselective transport in the present study. The permselectivity for the control nanofiber membrane was hardly dependent on the substrate concentration and gave unity at any initial feed concentrations. The dependence of flux on ini-
Fig. 7. Effect of substrate concentrations on the transport of racemic Glu through Z-d-Glu imprinted nanofiber membrane (a), control nanofiber membrane (b), and Z-l-Glu imprinted nanofiber membrane (c).
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Table 2 Results of chiral separation with molecularly imprinted nanofiber membranes (MINFM’s)a . 103 Cb
Z-d-Glu imprinted MINFM
Control NFM
mol dm
˛D/L
u
˛D/L
u
˛L/D
uc
0.25 0.50 1.00 Ed
1.45 1.27 1.11 2.30
1.96 × 10−9 (290) 1.04 × 10−9 (154) 5.49 × 10−10 (81.2) 6.76 × 10−12 (1)
∼1 ∼1 ∼1
1.98 × 10−9 (293) 2.04 × 10−9 (302) 1.70 × 10−9 (251)
1.44 1.34 1.07 2.30
3.81 × 10−9 (564) 2.49 × 10−9 (368) 1.32 × 10−9 (195) 6.76 × 10−12 (1)
3
a b c d
c
Z-l-Glu imprinted MINFM c
Figures in parentheses are the relative values; the u value for E being set as unity. A concentration gradient was applied as a driving force for membrane transport. u = (−J/c)/(d/dx) [{(mol cm cm−2 h−1 )/(mol cm−3 )}/(J mol−1 cm−1 ) = mol cm cm2 J−1 h−1 ]. A potential difference was applied as a driving force for membrane transport; cited from the previous results [11].
tial feed concentration also supported the transport mechanism mentioned above; in other words, the flux through the molecularly imprinted nanofiber membranes showed nonlinear relationship to the substrate concentration. The slope of the flux dependence on substrate concentration decreased with the increase in the feed concentration and reached asymptotically to a certain value. Contrary to this, the flux through the control nanofiber membrane was linearly increased with the substrate concentration and the relationship passed through the origin. In membrane separation, not only permselectivity but also flux is an important membrane performance as described before. In a sense, development of membrane with high flux value is more important than that with high permselectivity. Table 2 summarizes membrane performance studied in the present study and that previously reported [11]. In the present study, membrane transport was studied adopting concentration gradient as a driving force for membrane transport, while potential difference was adopted as a driving force for membrane transport in the previous study [11]. In order to compare flux values for those membranes each other, the molar mobility, u (mol cm cm2 J−1 h−1 ), of Glu for each membrane was determined by the following equation [40]: u=
(−J/c) (d/dx)
(6)
where J means the sum of d-Glu and l-Glu fluxes, c is the concentration of each Glu in the upstream side, and d/dx is the potential gradient at that point. The molar mobility u is defined as the mobility and is simply the flux per unit force, per unit concentration, and per unit membrane thickness. In the parentheses in Table 2, the relative molar mobility for each membrane, which is relative to that of previous results [11], is also given for convenience. In the calculation of the electrochemical potential difference due to the concentration gradient, the concentration of permeant (Glu) in the downstream side was determined to be 1.0 × 10−8 mol dm−3 . Because the lowest limit of the detection of Glu in the present study was the concentration of around 1.0 × 10−8 mol dm−3 . As can be seen in Table 2, flux values for the molecularly imprinted nanofiber membranes were one to two orders of magnitude higher than the previous results for molecularly imprinted membranes [11]. In membrane separation, the flux value and the corresponding permselectivity often showed a trade-off relationship. Against this, the present molecularly imprinted nanofiber membranes still gave permselectivity as observed in chiral separation with molecularly imprinted nanofiber membranes from carboxylated polysulfone [34]. As described in the previous Section 3.3, against expectation, the amount of molecular recognition sites constructed by the print molecule was very low in the present study. There might be three plausible methods to further enhance both permselectivity and flux of molecularly imprinted nanofiber membrane; (1) narrowing diameter of molecularly imprinted nanofiber membrane, which will lead to the increase in surface area (surface-to-volume ratio) and narrowing mesh size between nanofibers, (2) localization of molecular recognition sites on the
surface of nanofiber, which could be achieved by applying coaxial, two-capillary spinneret [27,28,36–38], or (3) applying a higher molecular imprinting ratio. In the present paper, the authors reported the potential of molecularly imprinted nanofiber membranes, which would give both higher permselectivity and throughput (flux), in other words, a breakthrough of membrane performance, trade-off relationship in membrane separation, would be realized by applying molecularly imprinted nanofiber membranes as separation membranes. 4. Conclusions Molecularly imprinted nanofiber membranes, which are expected to open a door to novel separation membrane forms, were prepared from cellulose acetate (CA) and a derivative of optically pure glutamic acid, such as Z-d-Glu or Z-l-Glu, as a print molecule by simultaneously applying an alternative molecular imprinting and an electrospray deposition. The results obtained in the present study suggested that molecularly imprinted nanofiber membranes enhance both permselectivity and flux, which are generally perceived to show a trade-off relationship. The flux values for the present molecularly imprinted nanofiber membranes were about two orders of magnitude higher than the usual molecularly imprinted membranes. However, the molecularly imprinted nanofiber membranes gave permselectivity. The present study revealed that molecularly imprinted nanofiber membranes have potential that both permselectivity and flux can be simultaneously enhanced. References [1] W.S.W. Ho, K.K. Sirkar, Membrane Handbook, Chapman & Hall, New York, 1992. [2] M. Mulder, Basic Principles of Membrane Technology, 2nd ed., Kluwer Academic Publishers, Dordrecht, 1996. [3] R.W. Baker, Membrane Technology and Applications, 2nd ed., John Wiley & Sons, 2004. [4] A.S. Michaels, R.F. Baddour, H.J. Bixler, C.Y. Choo, Conditioned polyethylene as a permselective membrane, Ind. Eng. Chem. Process Des. Dev. 1 (1962) 14–25. [5] M.V. Polyakov, Adsorption properties of silica gel and its structure, Zhur. Fiz. Khim. 2 (1931) 799–805. [6] F.H. Dickey, The preparation of specific adsorbents, Proc. Natl. Acad. Sci. USA 35 (1949) 227–229. [7] G. Wulff, A. Sarhan, The use of polymers with enzyme-analogous structures for the resolution of racemates, Angew. Chem. Internat. Edit. 11 (1972) 341 [Angew. Chem. 84 (1972) 364]. [8] R. Arshady, K. Mosbach, Synthesis of substrate-selective polymers by host–guest polymerization, Makromol. Chem. 182 (1981) 687–692. [9] M. Yoshikawa, J. Izumi, T. Ooi, T. Kitao, M.D. Guiver, G.P. Robertson, Carboxylated polysulfone membranes having a chiral recognition site induced by ban alternative molecular imprinting technique, Polym. Bull. 40 (1998) 517–524. [10] M. Yoshikawa, J. Izumi, Chiral recognition sites converted from tetrapeptide derivatives adopting racemates as print molecules, Macromol. Biosci. 3 (2003) 487–498. [11] M. Yoshikawa, T. Ooi, J. Izumi, Alternative molecularly imprinted membranes from a derivative of natural polymer, cellulose acetate, J. Appl. Polym. Sci. 72 (1999) 493–499. [12] M. Yoshikawa, K. Kawamura, A. Ejima, T. Aoki, S. Sakurai, K. Hayashi, K. Watanabe, Green polymers from Geobacillus thermodinitrificans DSM465–Candidates for molecularly imprinted materials, Macromol. Biosci. 6 (2006) 210–215.
Y. Sueyoshi et al. / Journal of Membrane Science 357 (2010) 90–97 [13] M. Yoshikawa, Molecularly imprinted polymeric membranes for optical resolution, in: R.A. Bartsch, M. Maeda (Eds.), Molecular and Ionic Recognition with Imprinted Polymers, ACS-Symp. Ser., vol. 703, ACS, Washington, DC, 1998, p. 170. [14] M. Yoshikawa, Molecularly imprinted polymeric membranes, Bioseparation 10 (2002) 277–286. [15] F. Trotta, E. Drioli, C. Baggiani, D. Lacopo, Molecular imprinted polymeric membrane for naringin recognition, J. Membr. Sci. 201 (2002) 77–84. [16] Y. Kanekiyo, R. Naganawa, H. Tao, Molecular imprinting of bisphenol A and alkylphenols using amylose as a host matrix, Chem. Commun. (2002) 2698–2699. [17] M. Ramamoorthy, M. Ulbricht, Molecular imprinting of cellulose acetatesulfonated polysulfone blend membranes for Rhodamine B by phase inversion technique, J. Membr. Sci. 217 (2003) 207–214. [18] C. Cristallini, G. Ciardelli, N. Barbani, P. Giusti, Acrylonitrile-acrylic acid copolymer membrane imprinted with uric acid for clinical uses, Macromol. Biosci. 4 (2004) 31–38. [19] F. Trotta, C. Baggiani, M.P. Luda, E. Drioli, T. Massari, A molecular imprinted membrane for molecular discrimination of tetracycline hydrochloride, J. Membr. Sci. 254 (2005) 13–19. [20] K. Takeda, T. Kobayashi, Hybrid molecularly imprinted membranes for targeted bisphenol derivatives, J. Membr. Sci. 275 (2006) 61–69. [21] Z. Jiang, Y. Yu, H. Wu, Preparation of CS/GPTMS hybrid molecularly imprinted membrane for efficient chiral resolution of phenylalanine isomers, J. Membr. Sci. 280 (2006) 876–882. [22] C.K.M. Faizal, Y. Hoshina, T. Kobayashi, Scaffold membranes for selective adsorption of ␣-tocopherol by phase inversion covalently imprinting technique, J. Membr. Sci. 322 (2008) 503–511. [23] G.M.H. Meesrers, P.H.W. Vercoulen, J.C.M. Marijnissen, B. Scarlett, Generation of micron-sized droplets from the taylor cone, J. Aerosol Sci. 23 (1992) 37–49. [24] J. Doshi, D.H. Reneker, Electrospinning process and application of electrospun fibers, J. Electrost. 35 (1995) 151–160. [25] D.H. Reneker, I. Chun, Nanometer diameter fibers of polymer, produced by electrospinning, Nanotechnology 7 (1996) 216–223. [26] V.N Morozov, T.Y. Morozova, Electrospray deposition as a method to fabricate functionally active protein films, Anal. Chem. 71 (1999) 1415–1420.
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[27] S. Ramakrishna, K. Fujihara, W.-E. Teo, T.-C. Lim, Z. Ma, An Introduction to Electrospinning and Nanofibers, World Scientific, Singapore, 2005. [28] A. Greiner, J.H. Wendorff, Electrospinning: a fascinating method for the preparation of ultrathin fibers, Angew. Chem. Int. Ed. 46 (2007) 5670–5703. [29] K. Yoon, B.S. Hsiao, B. Chu, Functional nanofibers for environmental applications, J. Mater. Chem. 18 (2008) 5326–5334. [30] B. Chu, B.H. Hsiao, The role of polymers on breakthrough technologies for water purification, J. Polym. Sci.: Part B: Polym. Phys. 47 (2009) 2431–2435. [31] I.S. Chronakis, B. Milosevic, A. Frenot, L. Ye, Generation of molecular recognition sites in electrospun polymer nanofibers via molecular imprinting, Macromolecules 39 (2006) 357–361. [32] I.S. Chronakis, A. Jakob, B. Hagström, L. Ye, Encapsulation and selective recognition of molecularly imprinted theophylline and 17-estradiol nanoparticles within electrospun polymer nanofibers, Langmuir 22 (2006) 8960–8965. [33] K. Yoshimatsu, L. Ye, J. Lindberg, I.S. Chronakis, Selective molecular adsorption using electrospun nanofiber affinity membranes, Biosens. Bioelectron. 23 (2008) 1208–1215. [34] M. Yoshikawa, K. Nakai, H. Matsumoto, A. Tanioka, M.D. Guiver, G.P. Robertson, Molecularly imprinted nanofiber membranes from carboxylated polysulfone by electrospray deposition, Macromol. Rapid Commun. 28 (2007) 2100–2105. [35] J.A. Riddick, W.B. Bunger, T.K. Sakano, Organic Solvents, 4th ed., John Wiley & Sons, New York, 1986. [36] Z. Sun, E. Zussman, A.L. Yarin, J.H. Wendorff, A. Greiner, Compound core–shell polymer nanofibers by co-electrospinning, Adv. Mater. 15 (2003) 1929–1932. [37] D. Li, Y. Xia, Direct fabrication of composite and ceramic hollow nanofibers by electrospinning, Nano Lett. 4 (2004) 933–938. [38] D. Li, J. McCann, Y. Xia, Use of electrospinning to directly fabricate hollow nanofibers with functionalized inner and outer surfaces, Small 1 (2005) 83–86. [39] K. Taniwaki, A. Hyakutake, T. Aoki, M. Yoshikawa, M.D. Guiver, G.P. Robertson, Evaluation of the recognition ability of molecularly imprinted materials by surface plasmon resonance (SPR) spectroscopy, Anal. Chim. Acta 489 (2003) 191–198. [40] S.G. Schultz, Basic Principles of Membrane Transport, Cambridge University Press, Cambridge, 1980.
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Journal of Membrane Science journal homepage: www.elsevier.com/locate/memsci
Molecularly imprinted nanofiber membranes from cellulose acetate aimed for chiral separation Yuuki Sueyoshi, Chiho Fukushima, Masakazu Yoshikawa ∗ Department of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Kyoyo 606-8585, Japan
a r t i c l e
i n f o
Article history: Received 11 March 2010 Received in revised form 31 March 2010 Accepted 2 April 2010 Available online 10 April 2010 Keywords: Adsorption isotherm Chiral separation Membrane Molecularly imprinted membrane Molecular imprinting Molecular recognition Optical resolution Permselectivity
a b s t r a c t Permselectivity and throughput (flux) are important specificity in membrane separation. It is an ultimate dream for membranologists to simultaneously enhance not only permselectivity but also flux, which generally show a trade-off relationship. A breakthrough in membrane separation would be realized by adopting membranes with higher surface area, which leads to higher molecular recognition site concentration, and higher porosity. Such separation membranes would be obtained by applying an electrospray deposition technique. To this end, in the present paper, molecularly imprinted nanofiber membranes were prepared from cellulose acetate (CA) and a print molecule, a derivative of optically pure glutamic acid, such as N-␣-benzyloxycarbonyl-d-glutamic acid (Z-d-Glu) or N-␣-benzyloxycarbonyl-lglutamic acid (Z-l-Glu). Membrane performance of molecularly imprinted nanofiber membranes and usual molecularly imprinted membranes was compared in terms of adsorption selectivity, affinity constant, permselectivity, and flux. The results obtained in the present study revealed that electrospray deposition would be one of plausible methods to construct separation membranes to simultaneously enhance permselevtivity and flux. © 2010 Elsevier B.V. All rights reserved.
1. Introduction Membrane separation, which can be operated continuously under mild conditions, is regarded as an ultimate energy-saving separation technology [1]. Its selectivity and efficiency (flux) are greatly dependent on a couple of factors [1–3]. One is solubility or partition; the term of solubility is applicable to the case of a dense membrane and that of partition to the case of a porous membrane. In other words, the term of solubility or partition means a kind of affinity between a membrane and a target substrate to be separated. The other is diffusivity of the given substrate in the membrane, in other words, migration of the target substrate from upstream side to the downstream side in the membrane. The diffusivity is mainly governed by dimension and/or shape of the given substrate. From this, the range of diffusivity is thought to be intrinsically limited. Contrary to diffusivity, affinity between the membrane and the substrate, which is so-called molecular recognition, is theoretically ranges from naught to infinity, depending on the chemical nature of the given substrate, and the combination of a target molecule and a membrane material. The introduction of molecular recognition site into a membrane is indispensable so that its permselectivity toward a target molecule can be improved.
∗ Corresponding author. Tel.: +81 75 724 7816; fax: +81 75 724 7800. E-mail address: [email protected] (M. Yoshikawa). 0376-7388/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.memsci.2010.04.005
Among plausible methods, molecular imprinting is a facile way to introduce molecular recognition sites into polymeric materials and membranes. The first application of molecular imprinting to membrane preparation was reported by Michaels and his coworkers in 1962 [4]. In the pioneering study [4], pervaporation membranes for the separation of xylene isomers were prepared from polyethylene, adopting xylene isomer (o-, m-, or p-xylene) as a print molecule. In the last part of the paper, they described that the application of molecular imprinting was not restricted to pervaporation membrane preparation and similar membrane formation process was applicable in other membrane separation area, such as gas or vapor separation and dialysis. Contrary to conventional molecular imprinting, which was studied in the preparation of molecularly imprinted silicas in the early days [5,6] and polymeric materials with specific binding sites toward a given target molecule since 1972 [7,8], Michales’ paper showed possibility that polymeric materials were directly converted into membranes having molecular recognition sites, even though starting raw materials had no specific binding sites toward target substrates. The authors’ research group extended Michales’ study to any polymeric materials, which can construct given structures and retain their forms, such as synthetic polymers [9], oligopeptide derivatives [10], derivative of natural polymers [11], and natural polymers [12]. Those polymeric materials were directly converted into materials or membranes with molecular recognition sites toward the print molecule or the print molecule analogue. Such
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method was named an alternative molecular imprinting [13,14]. The usefulness and potential of the facile method, an alternative molecular imprinting, converting polymeric materials having no specific binding sites into molecular recognition materials has been recognized by researchers and the method has been adopted for the preparation of membranes and other materials with molecular recognition sites [15–22]. As described above, an alternative molecular imprinting is a facile way to obtain membrane with specific binding sites toward a targeted substrate. However neither flux nor permselectivity of those membranes were enough for industrial applications. The enhancement of flux, in other words, throughput was especially indispensable. Molecularly imprinted membranes with a higher surface area and higher porosity are required to give both higher flux and permselectivity. Electrospray deposition is a suitable or the best method to obtain molecularly imprinted membranes with a large surface area. Electrospray deposition is expected to provide membranes consisting of polymeric nanofibers with diameters ranging from a few nanometers to several micrometers through the action of external electric field imposed on a polymeric solution or melt [23–30]. Electrosprayed nanofiber membranes with molecular recognition sites were first studied by applying an alternative molecular imprinting [31], and the mixture of polyallylamine and poly(ethylene terephthalate) was converted into molecular recognition materials to recognize 2,4-dichlorophenoxyacetic acid. Molecularly imprinted nanoparticles were also converted into electrosprayed nanofiber membranes with poly(ethylene terephthalate) [32,33]. Possibility of the enhancement of flux without the depression of permselectivity was proved by molecularly imprinted nanofiber membranes, which were fabricated from carboxylated polysulfone and N-␣-benzyloxycarbonyl-d-glutamic acid (Z-d-Glu) or N-␣-benzyloxycarbonyl-l-glutamic acid (Z-l-Glu) as a print molecule [34]. In membrane separation, flux values and permselectivies often showed a trade-off relationship. It is thought to be hard or impossible to simultaneously increase both flux value and permselectivity. Such a trade-off relationship in membrane separation is an indispensable task to be solved or is thought to be an eternal unsolved problem. However, the previous study [34] revealed that the molecularly imprinted nanofiber membranes have potential to simultaneously enhance a couple of important membrane performance, such as permselectivities and flux values. The form of molecularly imprinted nanofiber membrane is expected to simultaneously give higher flux value and permselectivity. In the present study, a derivative of natural polymer, cellulose acetate, was adopted as a candidate material for molecularly imprinted nanofiber membranes, and their membrane performance was compared with that of usual molecularly imprinted membrane previously reported [11] in terms of adsorption selectivity, affinity constant between a target molecule and molecular recognition site in the membrane, permselectivity, and flux through the membrane. 2. Experimental
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method [35]. Water purified with an ultrapure water system (Simpli Lab, Millipore S.A., Molsheim, France) was used. 2.2. Preparation of molecularly imprinted nanofiber membranes In the present study, the molecular imprinting ratio, which was the mole ratio of print molecule to constitutional repeating unit of cellulose acetate in the membrane preparation process, was fixed to be 0.50 so that the results obtained in the present study can be compared with the previous results [11]. DMF was adopted as a solvent and the polymer concentration was fixed at 30.0 wt.% in the present study. Esprayer ES-2000 (Fuence Co. Ltd., Wako, Japan) was adopted as the electrospray deposition device. Polymer solution containing either one of the print molecules was elctrosprayed at ambient temperature using an applied voltage of 30.0 kV. The syringe used in the present study had a capillary tip of 0.52 mm diameter. The feeding rate was fixed to be 1.0 mm3 min−1 . A grounded aluminum foil used as a counter electrode was placed 10 cm from the tip of the capillary. The thickness of the electrosprayed molecularly imprinted membrane with Z-d-Glu was determined to be 120 m, while that with Z-l-Glu to be 300 m. The print molecule was removed from the resultant nanofiber membranes by methanol until the print molecule could be hardly detected in methanol by UV analysis. The preparation of control nanofiber membrane was prepared from 40.0 wt.% DMF solution at the feeding rate of 0.50 mm3 min−1 . Other electrospray deposition conditions were same as those for the preparation of molecularly imprinted nanofiber membranes. The thickness of electrosprayed control membrane was determined to be 90 m. The morphology, diameter, and thickness of the electrosprayed molecularly imprinted nanofiber membranes were determined with a Hitachi S-3000 scanning electron microscope (SEM). A small section of the membrane was placed on the SEM sample holder. 2.3. Adsorption selectivity The membrane samples were immersed in a racemic Glu solution, which was the same racemic mixture studied in the membrane transport (i.e., a 50 vol. % aqueous ethanol solution of racemic Glu, with concentrations of 2.50 × 10−4 , 5.00 × 10−4 , or 1.00 × 10−3 mol dm−3 ) and the mixture was allowed to be equilibrated at 40 ◦ C. Quantitative measurements of aliquots of the solution at the initial stage and after equilibrium had been reached were made using HPLC employing a Chiralpak MA(+) column (50 mm × 4.6 mm (i.d.)) (Daicel Chemical Ind. Ltd.). The amount of Glu in the supernatant subtracted from the amount initially in the solution gave the amount of Glu adsorbed in the membrane. The adsorption selectivity SA(i/j) is defined as
SA(i/j) =
(i-Glu)/(j-Glu) [i-Glu]/[j-Glu]
(1)
where (i-Glu) and [i-Glu] are the amount of i-Glu adsorbed in the membrane and concentration in the solution after equilibrium had been reached, respectively.
2.1. Materials 2.4. Adsorption isotherms of d-Glu and l-Glu Cellulose acetate (CA), of which acetyl content was 40%, was purchased from Wako Pure Chemical Industries, Ltd. and used without purification. N-␣-Benzyloxycarbonyl-d-glutamic acid (Z-d-Glu) or N-␣-benzyloxycarbonyl-l-glutamic acid (Z-l-Glu), purchased from Watanabe Chemical Industries, Ltd. (Hiroshima, Japan), was used as a print molecule without further purification. d-Glutamic acid (dGlu), l-glutamic acid (l-Glu), sodium azide, copper sulfate, ethanol were obtained from commercial sources and used as received. N,N-Dimethylformamide (DMF) was purified by the conventional
The membrane samples were immersed in various concentrations of pure d-Glu or l-Glu solution and allowed to equilibrate at 40 ◦ C. The quantitative analyses were done as described above. The concentration of Glu in the membrane [i-Glu]M or [j-Glu]M (i = D, j = L or i = L, j = D) was determined adopting the amount of Glu adsorbed in the membrane and the volume of membrane phase, including that of membrane and that of the solution in the membrane.
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2.5. Enantioselective membrane transport A membrane with an area of 3.0 cm2 was tightly secured with Parafilm between two chambers of a permeation cell. The volume of each chamber was 40.0 cm3 . A racemic Glu solution was placed in the left-hand side chamber (L-side) and aqueous ethanol solution in the right-hand side (R-side). Each concentration of racemic Glu was 2.50 × 10−4 , 5.00 × 10−4 , or 1.00 × 10−3 mol dm−3 . Permeation experiments were carried out at 40 ◦ C with stirring. An aliquot was drawn from the permeate side at each sampling time. The amounts of d- and l-Glu transported through the membrane were determined by HPLC as described above. The flux, J (mol cm cm−2 h−1 ), is defined as J=
Qı At
(2)
where Q [mol] is the amount of transported Glu, ı [cm] the membrane thickness, A [cm2 ] the effective membrane area, and t [h] means the time. The permselectivity ˛i/j is defined as the flux ratio, Ji /Jj , divided by the concentration ratio [i-Glu]/[j-Glu] ˛i/j =
(Ji /Jj ) ([i-Glu]/[j-Glu])
(3)
3. Results and discussion 3.1. Morphology of molecularly imprinted nanofiber membranes The SEM photographs of the electrosprayed nanofiber membranes and the control nanofiber membrane are shown in Fig. 1. The nanofiber membrane shown in Fig. 1(a) was electrosprayed in the presence of Z-d-Glu as a print molecule. That shown in Fig. 1(b) was fabricated adopting Z-l-Glu as a print molecule. Fig. 1(c) shows the SEM image of the control nanofiber membrane, which was electrosprayed without a print molecule. As reported, the morphology and the diameter of the electrosprayed nanofiber membranes would be widely controlled [26–28]. A strict optimization of electrospray condition has not been conducted in the present study. The diameters of molecularly imprinted nanofiber membranes were determined to be 200–500 nm and that of the control membrane to be 300–800 nm. 3.2. Adsorption selectivity of racemic Glu The dependence of adsorption of racemic Glu on substrate concentrations is summarized in Fig. 2. The results for Z-d-Glu imprinted nanofiber membrane is shown in Fig. 2(a) and those for Z-l-Glu imprinted one in Fig. 2(e), respectively. That for the control nanofiber membrane is shown in Fig. 2(c). In Fig. 2(a), (c), and (e), each amount of Glu adsorbed by the membrane is given as a relative value (relative to that of the constitutional repeating unit of CA). Two types of molecularly imprinted nanofiber membrane showed adsorption selectivity, in other words, chiral recognition ability, while the control nanofiber membrane hardly showed adsorption selectivity. The nanofiber membrane imprinted by Z-d-Glu recognized the d-isomer in preference to the corresponding l-isomer and vice versa, as observed in molecularly imprinted CA membranes [11]. The dependence of adsorption selectivity on the substrate concentration is shown in Fig. 2(b) and (f). The adsorption selectivities for both nanofiber membranes (SA(i/j) ) increased with the decrease in the substrate concentrations from 1.00 × 10−3 mol dm−3 to 2.50 × 10−4 mol dm−3 , implying that there can be found molecular recognition sites, which were constructed by the presence of the print molecule, Z-d-Glu or Z-l-Glu, during the electrospray deposition process, in the electrosprayed
Fig. 1. SEM images of surface of Z-d-Glu imprinted nanofiber membrane (a), Z-l-Glu imprinted nanofiber membrane (b), and control nanofiber membrane (c).
nanofiber membranes. Contrary to this, the adsorption selectivity for the control nanofiber membrane was hardly dependent on the substrate concentration as shown in Fig. 2(d). 3.3. Adsorption isotherms of d-Glu and l-Glu Parameters for adsorption of Glu in the molecularly imprinted nanofiber membranes could be determined by using the experimental data obtained in the adsorption selectivity study summarized in Fig. 2. Because the molecular recognition site, which was formed by the presence of the print molecule, incorporated the isomer, of which absolute configuration was same as that of the print molecule. Contrary to this, the antipode was not adsorbed in the formed molecular recognition site. Non-specific adsorption of each enantiomer of Glu, which was an adsorption without any specific interaction, was occurred without the interference of nonspecific adsorption of antipode. In the present study, adsorption isotherms of pure d-Glu and pure l-Glu in molecularly imprinted nanofiber membranes were investigated since the authors judged that parameters for adsorption determined by using adsorption isotherms were more exact than those by using the adsorption selectivity data. The adsorption isotherms for the molecularly imprinted nanofiber membranes are shown in Fig. 3. The adsorption isotherm
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Fig. 2. Effect of the substrate concentrations on Glu adsorption (a, c, and e) and adsorption selectivity (b, d, and f) for Z-d-Glu imprinted membrane (a and b), control one (c and d), and Z-l-Glu imprinted one (e and f). (The two data of Glu adsorption in (c) are superimposed and not distinguishable.).
for l-Glu in Fig. 3(a) and that for d-Glu in Fig. 3(b) are straight lines passing through the origin, implying that the l-isomer in the disomer-selective adsorption nanofiber membrane (Fig. 3(a)) and the d-isomer in the l-isomer-selective adsorption one (Fig. 3(b)) were adsorbed without any specific interaction with the membrane. This can be anticipated from the results that the Z-d-Glu imprinted nanofiber membrane showed d-isomer adsorption selectivity, while the Z-l-Glu imprinted one recognized the lisomer in preference to the corresponding d-Glu as shown in Fig. 2. The isotherm of Glu adsorbed non-specifically in the nanofiber membrane can be represented by the following equation: [j-Glu]M = kA [j-Glu]
(4)
where j means the enantiomer of Glu adsorbed non-specifically in the nanofiber membrane, [j-Glu]M is the concentration of j-isomer of Glu adsorbed non-specifically in the membrane, kA denotes the adsorption constant, and [j-Glu] is the concentration for j-isomer of Glu in the solution equilibrated with the nanofiber membrane. On the other hand, the adsorption isotherm of d-Glu in Fig. 3(a) and that of l-Glu in Fig. 3(b) gave complicated profiles. Those target molecules were preferentially incorporated into each nanofiber
membrane. The straight lines over the substrate concentration of 5.0 × 10−4 mol dm−3 are almost parallel to those of enantiomers non-specifically adsorbed in each membrane. And the extension of those straight lines does not pass through the origin, and has positive intercept. Those adsorption isotherms exhibit dual adsorption isotherms, which consist of non-specific adsorption and adsorption on specific recognition sites toward d-isomer (Fig. 3(a)) or l-isomer (Fig. 3(b)). The isotherm of Glu adsorbed specifically in the membrane can be represented by the following equation: [i-Glu]M = kA [i-Glu] +
KS [Site]0 [i-Glu] 1 + KS [i-Glu]
(5)
where [i-Glu]M means the concentration of i-isomer of Glu adsorbed preferentially in the molecularly imprinted nanofiber membrane, KS is the affinity constant between the i-isomer and the molecular (chiral) recognition site, [Site]0 is the concentration of molecular recognition site in the membrane, and [i-Glu] denotes the concentration of i-isomer of Glu in the solution equilibrated with the nanofiber membrane. Two parameters in those adsorption equations (Eqs. (4) and (5)), which were determined
Fig. 3. Adsorption isotherms of d-Glu and l-Glu in the nanofiber membrane imprinted by Z-d-Glu (a) and the nanofiber membrane imprinted by Z-l-Glu (b). The mole ratio of print molecule to CA in the electrospray deposition process was fixed to be 0.50: kA = 1.5 × 10; [Site]0 = 7.0 × 10−3 mol dm−3 ; KS = 1.6 × 104 mol−1 dm3 for (a) and kA = 1.8 × 10; [Site]0 = 8.0 × 10−3 mol dm−3 ; KS = 1.7 × 104 mol−1 dm3 for (b).
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Y. Sueyoshi et al. / Journal of Membrane Science 357 (2010) 90–97 Table 1 Parameters for adsorption isotherms. Z-d-Glu imprinted mem. a
KA [Site]0 /mol dm−3 Ks /(mol−1 dm3 ) a b
Z-l-Glu imprinted mem. b
MIPM
MINFM
MIPMa
MINFMb
1.9 × 103 3.4 3.1 × 103
1.5 × 10 7.0 × 10−3 1.6 × 104
2.0 × 103 3.4 3.1 × 103
1.8 × 10 8.0 × 10−3 1.7 × 104
Molecularly imprinted membrane; the data were cited from the previous results [11]. Molecularly imprinted nanofiber membrane.
Fig. 4. Tentative scheme of electrospray deposition in the present study, where CA and Z-Glu (print molecule) were simultaneously electrosprayed.
to fit each adsorption isotherm in Fig. 3 best, are summarized in Table 1 together with those for previous molecularly imprinted membranes [11]. The concentration of molecular recognition sites, which were constructed by the presence of the print molecule during the electrospray deposition process, for Z-d-Glu imprinted nanofiber membrane was determined to be 7.0 × 10−3 mol dm−3 and that
for Z-l-Glu imprinted one to be 8.0 × 10−3 mol dm −3 , respectively. On the other hand, the concentrations of the previous molecularly imprinted CA membranes were determined to be ca. 3.4 mol dm−3 [11]. Against our expectation, the amounts of molecular recognition site in the molecularly imprinted nanofiber membranes were lower than that for the previous molecularly imprinted CA membrane, even though the surface area of the present nanofiber membrane was higher than that for the previous dense membrane. This can lead to the conclusion that the amount of Z-d-Glu or Z-l-Glu, which worked as a print molecule in electrospray deposition process, was less than that in the previous study [11]. This can be explained as follows: as shown in Fig. 4, in the electrospray deposition process of CA and Z-d-Glu or Z-l-Glu, most print molecule Z-Glu was solely sprayed toward the counter electrode of grounded aluminum foil accompanying with no CA molecule. As a result, small amount of the print molecule was electrosprayed together with CA molecule toward the collector. In other words, the molecular imprinting ratio, which is defined as the mole ratio of the print molecule to the constitutional repeating unit of CA, for the preparation of the molecularly imprinted nanofiber membrane was lower than that for the previous molecularly imprinted membrane. The above speculation can be supported by the affinity constants for two types of molecularly imprinted membrane, such as a molecularly imprinted nanofiber membrane and a usual molecularly imprinted membrane. The affinity constant KS for the present nanofiber membranes were determined to be 1.6 × 104 mol−1 dm3 for Z-d-Glu imprinted nanofiber membrane and 1.7 × 104 mol−1 dm3 for Z-l-Glu imprinted one, respectively. Those for the previous molecularly imprinted CA membranes were determined to be 3.1 × 103 mol−1 dm3 [11], which were less than
Fig. 5. Schematic image of the relationship between molecular imprinting ratio and interaction mode (affinity constant).
Y. Sueyoshi et al. / Journal of Membrane Science 357 (2010) 90–97
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Fig. 6. Time-transport curves of racemic Glu through the molecularly imprinted and control nanofiber membranes. (The molecular imprinting ratio, (Z-Glu)/(CA), was fixed to be 0.50; [d-Glu]L,0 = [l-Glu]L,0 = 2.50 × 10−4 mol dm−3 .)
20% of those for the present molecularly imprinted nanofiber membranes. As schematically shown in Fig. 5, the affinity constant for the molecular recognition site constructed by the print molecule and the target molecule would depend on the molecular imprinting condition (molecular imprinting ratio) and KS was increased with the decrease in the imprinting ratio (Z-Glu)/(CA) [39]. At the low molecular imprinting ratio, more functional groups interacted with one print molecule, resulting in a higher affinity constant. As a result, the affinity constant gave higher values with the decrease in the molecular imprinting ratio. This means that the amount of the print molecule effectively worked during the electrospray deposition was lower than that during previous molecular imprinting process. 3.4. Enantioselective transport of racemic Glu From the results of enantioselective adsorption studied in the previous section, those two types of molecularly imprinted nanofiber membrane were expected to show enantioselective transport ability. To this end, enantioselective transport of racemic Glu through the two types of molecularly imprinted nanofiber membrane and the control nanofiber membrane were investigated. As examples of time-transport curves for those membranes, those for the initial feed concentration of 2.50 × 10−4 mol dm−3 are shown in Fig. 6. As expected from previous results [11] and adsorp-
tion phenomena shown in Figs. 2 and 3, d-Glu was transported through the Z-d-Glu molecularly imprinted nanofiber membrane in preference to the corresponding l-isomer of Glu and vice versa. The permselectivity toward the d-Glu for the Z-d-Glu molecularly imprinted nanofiber membrane was determined to be 1.45, while that for Z-l-Glu molecularly imprinted one to be 1.44. Contrary to this, the control nanofiber membrane, which was electrosprayed without a print molecule, hardly showed permselectivity toward racemic Glu mixture. The dependence of permselectivity on the initial concentration in the feed side will give the insight into the transport mechanism; in other words, the permselectivity would be expected to increase with the decrease in feed concentration in the case that the molecular recognition sites in the nanofiber membrane, which were constructed during electrospraying process, contributed as specific recognition sites in the membrane transport. Fig. 7 shows relationship between permselectivity and flux dependence on feed concentration. As can be seen in the figure, permselectivity of molecularly imprinted nanofiber membranes was increased with the decrease in feed concentration, implying that the molecular recognition sites in the molecularly imprinted nanofiber membrane contributed to enantioselective transport in the present study. The permselectivity for the control nanofiber membrane was hardly dependent on the substrate concentration and gave unity at any initial feed concentrations. The dependence of flux on ini-
Fig. 7. Effect of substrate concentrations on the transport of racemic Glu through Z-d-Glu imprinted nanofiber membrane (a), control nanofiber membrane (b), and Z-l-Glu imprinted nanofiber membrane (c).
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Y. Sueyoshi et al. / Journal of Membrane Science 357 (2010) 90–97
Table 2 Results of chiral separation with molecularly imprinted nanofiber membranes (MINFM’s)a . 103 Cb
Z-d-Glu imprinted MINFM
Control NFM
mol dm
˛D/L
u
˛D/L
u
˛L/D
uc
0.25 0.50 1.00 Ed
1.45 1.27 1.11 2.30
1.96 × 10−9 (290) 1.04 × 10−9 (154) 5.49 × 10−10 (81.2) 6.76 × 10−12 (1)
∼1 ∼1 ∼1
1.98 × 10−9 (293) 2.04 × 10−9 (302) 1.70 × 10−9 (251)
1.44 1.34 1.07 2.30
3.81 × 10−9 (564) 2.49 × 10−9 (368) 1.32 × 10−9 (195) 6.76 × 10−12 (1)
3
a b c d
c
Z-l-Glu imprinted MINFM c
Figures in parentheses are the relative values; the u value for E being set as unity. A concentration gradient was applied as a driving force for membrane transport. u = (−J/c)/(d/dx) [{(mol cm cm−2 h−1 )/(mol cm−3 )}/(J mol−1 cm−1 ) = mol cm cm2 J−1 h−1 ]. A potential difference was applied as a driving force for membrane transport; cited from the previous results [11].
tial feed concentration also supported the transport mechanism mentioned above; in other words, the flux through the molecularly imprinted nanofiber membranes showed nonlinear relationship to the substrate concentration. The slope of the flux dependence on substrate concentration decreased with the increase in the feed concentration and reached asymptotically to a certain value. Contrary to this, the flux through the control nanofiber membrane was linearly increased with the substrate concentration and the relationship passed through the origin. In membrane separation, not only permselectivity but also flux is an important membrane performance as described before. In a sense, development of membrane with high flux value is more important than that with high permselectivity. Table 2 summarizes membrane performance studied in the present study and that previously reported [11]. In the present study, membrane transport was studied adopting concentration gradient as a driving force for membrane transport, while potential difference was adopted as a driving force for membrane transport in the previous study [11]. In order to compare flux values for those membranes each other, the molar mobility, u (mol cm cm2 J−1 h−1 ), of Glu for each membrane was determined by the following equation [40]: u=
(−J/c) (d/dx)
(6)
where J means the sum of d-Glu and l-Glu fluxes, c is the concentration of each Glu in the upstream side, and d/dx is the potential gradient at that point. The molar mobility u is defined as the mobility and is simply the flux per unit force, per unit concentration, and per unit membrane thickness. In the parentheses in Table 2, the relative molar mobility for each membrane, which is relative to that of previous results [11], is also given for convenience. In the calculation of the electrochemical potential difference due to the concentration gradient, the concentration of permeant (Glu) in the downstream side was determined to be 1.0 × 10−8 mol dm−3 . Because the lowest limit of the detection of Glu in the present study was the concentration of around 1.0 × 10−8 mol dm−3 . As can be seen in Table 2, flux values for the molecularly imprinted nanofiber membranes were one to two orders of magnitude higher than the previous results for molecularly imprinted membranes [11]. In membrane separation, the flux value and the corresponding permselectivity often showed a trade-off relationship. Against this, the present molecularly imprinted nanofiber membranes still gave permselectivity as observed in chiral separation with molecularly imprinted nanofiber membranes from carboxylated polysulfone [34]. As described in the previous Section 3.3, against expectation, the amount of molecular recognition sites constructed by the print molecule was very low in the present study. There might be three plausible methods to further enhance both permselectivity and flux of molecularly imprinted nanofiber membrane; (1) narrowing diameter of molecularly imprinted nanofiber membrane, which will lead to the increase in surface area (surface-to-volume ratio) and narrowing mesh size between nanofibers, (2) localization of molecular recognition sites on the
surface of nanofiber, which could be achieved by applying coaxial, two-capillary spinneret [27,28,36–38], or (3) applying a higher molecular imprinting ratio. In the present paper, the authors reported the potential of molecularly imprinted nanofiber membranes, which would give both higher permselectivity and throughput (flux), in other words, a breakthrough of membrane performance, trade-off relationship in membrane separation, would be realized by applying molecularly imprinted nanofiber membranes as separation membranes. 4. Conclusions Molecularly imprinted nanofiber membranes, which are expected to open a door to novel separation membrane forms, were prepared from cellulose acetate (CA) and a derivative of optically pure glutamic acid, such as Z-d-Glu or Z-l-Glu, as a print molecule by simultaneously applying an alternative molecular imprinting and an electrospray deposition. The results obtained in the present study suggested that molecularly imprinted nanofiber membranes enhance both permselectivity and flux, which are generally perceived to show a trade-off relationship. The flux values for the present molecularly imprinted nanofiber membranes were about two orders of magnitude higher than the usual molecularly imprinted membranes. However, the molecularly imprinted nanofiber membranes gave permselectivity. The present study revealed that molecularly imprinted nanofiber membranes have potential that both permselectivity and flux can be simultaneously enhanced. References [1] W.S.W. Ho, K.K. Sirkar, Membrane Handbook, Chapman & Hall, New York, 1992. [2] M. Mulder, Basic Principles of Membrane Technology, 2nd ed., Kluwer Academic Publishers, Dordrecht, 1996. [3] R.W. Baker, Membrane Technology and Applications, 2nd ed., John Wiley & Sons, 2004. [4] A.S. Michaels, R.F. Baddour, H.J. Bixler, C.Y. Choo, Conditioned polyethylene as a permselective membrane, Ind. Eng. Chem. Process Des. Dev. 1 (1962) 14–25. [5] M.V. Polyakov, Adsorption properties of silica gel and its structure, Zhur. Fiz. Khim. 2 (1931) 799–805. [6] F.H. Dickey, The preparation of specific adsorbents, Proc. Natl. Acad. Sci. USA 35 (1949) 227–229. [7] G. Wulff, A. Sarhan, The use of polymers with enzyme-analogous structures for the resolution of racemates, Angew. Chem. Internat. Edit. 11 (1972) 341 [Angew. Chem. 84 (1972) 364]. [8] R. Arshady, K. Mosbach, Synthesis of substrate-selective polymers by host–guest polymerization, Makromol. Chem. 182 (1981) 687–692. [9] M. Yoshikawa, J. Izumi, T. Ooi, T. Kitao, M.D. Guiver, G.P. Robertson, Carboxylated polysulfone membranes having a chiral recognition site induced by ban alternative molecular imprinting technique, Polym. Bull. 40 (1998) 517–524. [10] M. Yoshikawa, J. Izumi, Chiral recognition sites converted from tetrapeptide derivatives adopting racemates as print molecules, Macromol. Biosci. 3 (2003) 487–498. [11] M. Yoshikawa, T. Ooi, J. Izumi, Alternative molecularly imprinted membranes from a derivative of natural polymer, cellulose acetate, J. Appl. Polym. Sci. 72 (1999) 493–499. [12] M. Yoshikawa, K. Kawamura, A. Ejima, T. Aoki, S. Sakurai, K. Hayashi, K. Watanabe, Green polymers from Geobacillus thermodinitrificans DSM465–Candidates for molecularly imprinted materials, Macromol. Biosci. 6 (2006) 210–215.
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