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Cite this: DOI: 10.1039/c5cc03207e Received 17th April 2015, Accepted 26th May 2015
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Dual-template docking oriented molecular imprinting: a facile strategy for highly efficient imprinting within mesoporous materials† Yang Chen, Xinglin Li, Danyang Yin, Daojin Li, Zijun Bie and Zhen Liu*
DOI: 10.1039/c5cc03207e www.rsc.org/chemcomm
We present a new strategy, called dual-template docking oriented molecular imprinting (DTD-OMI), for facile and highly efficient imprinting within mesoporous materials. As compared with bulk imprinting, which is a widely used strategy, DTD-OMI did not require additional steps, but provided significantly improved imprinting efficiency and binding properties.
Molecularly imprinted polymers (MIPs) and mesoporous materials are both important advanced materials. MIPs, as synthetic receptors with antibody-like binding properties or enzyme-like catalytic activities, have been used as biomimetic materials in important applications ranging from sensing to separation to catalysis.1 Mesoporous materials, which possess highly ordered mesopores, have also gained enormous attention in catalysis, sensing and separation.2 Clearly, a combination of these two types of advanced materials will be highly desirable for prospective important applications due to the merits from both sides, particularly high specificity, high capacity and size-sieving effect. However, molecular imprinting within mesoporous materials is a challenging task. Although a large variety of imprinting strategies or approaches have been proposed, such as bulk imprinting,3 surface imprinting,4 oriented imprinting,5 epitope imprinting,6 Pickering emulsion imprinting,7 metal coordination,8 hierarchical imprinting,9 nanofabrication,10 and boronate affinity-based molecular imprinting,11 all these methods cannot be directly applied to molecular imprinting within mesoporous materials, because imprint molecules must be imprinted on the surface of mesopores. To fill the gap, three main approaches have been developed so far: (1) grafted surface imprinting,12 in which base mesoporous silica is first prepared and then surface imprinting was carried out to fabricate a thin imprinting layer onto the wall of the mesopores; (2) surface imprint-based dummy imprinting,13 in which an imprint-like surfactant was mixed with the mesopore-forming State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210093, China. E-mail: [email protected]; Fax: +86-25-8368-5639 † Electronic supplementary information (ESI) available. See DOI: 10.1039/c5cc03207e
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micelles so that the imprint was directly imprinted in the wall of mesopores; and (3) covalent bulk imprinting,14 in which a specially synthesized crosslinker that contains an imprint was used to form mesoporous silica and the imprint was removed by heating. However, these methods are associated with some drawbacks. For instance, all these methods required additional steps. More importantly, the efficiency of these methods has not been well investigated yet. Therefore, straightforward and efficient imprinting strategies or approaches are highly desirable. Herein we proposed a facile strategy, called dual-template docking oriented molecular imprinting (DTD-OMI), for highly efficient imprinting within mesoporous materials. The central concept of this strategy relied on two keys: (1) the template– template docking, and (2) oriented imprinting. This strategy is as simple as the procedure for preparing regular mesoporous materials. Meanwhile, it can provide high imprinting efficiency and highly desirable binding properties. Although this strategy is designed for the imprinting of charged targets, MIPs specific to uncharged target molecules can also be prepared using a charged analogue of the target as the imprint (dummy molecular imprinting). In this study, the benefits of DTD-OMI over other imprinting strategies particularly bulk imprinting as well as its feasibility for dummy molecular imprinting were well demonstrated. Feasibility for application to real samples was verified with the specific enrichment of adenosine from human urine by adenosine monophosphate (AMP)-imprinted MSNs. The DTD-OMI strategy can be expanded to other mesopore templates and imprinting templates. Thus, it opened up a new avenue to the facile and efficient synthesis of molecularly imprinted mesoporous materials. As a proof-of-principle, AMP-imprinted MCM-41 mesoporous silica nanoparticles (MSNs) were prepared in this study. The principle and procedure are illustrated in Scheme 1. Cetyltrimethylammonium bromide (CTAB) was used as a mesopore template. Rod-like CTAB micelles, which possess positive charges at the surface, were first formed. AMP, a negatively charged compound, was used as an imprint and added to the solution. Due to electrostatic attraction, the imprint molecules
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Scheme 1
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Schematic diagram of the DTD-OMI strategy.
were docked onto the surface of the CTAB micelles to form dual-template complexes. After that, an appropriate Si source precursor, a mixture containing tetraethoxysilane (TEOS), 3-aminopropyl triethoxysilane (APTES) and 3-aminophenylboronic acid appended 3-glycidyloxypropyl triethoxysilane (APBA-GPTES) in this study, was added to the solution. The precursor APBA-GPTES was produced from the reaction of a 1 : 1 stoichiometric mixture of APBA and GPTES (see more details in the ESI†). The co-condensation occurred around the dual-template complexes. Due to the template–template docking configuration, other functionalities of the template, including the ribose and adenine moieties, can interact with the functional monomers APBA-GPTES and APTES due to boronate affinity and hydrogen bonding, respectively (see Fig. S3, ESI† for details). Therefore, all the imprint molecules were imprinted in the wall of the mesopores with access to the mesopore template. After imprinting, by using Soxhlet extraction with a strong acidic solution, which is a regular template removal procedure for the preparation of MSNs, both the mesopore template and the imprinting template were efficiently removed simultaneously, because the covalent boronate affinity bonding can be disrupted under acidic conditions.15 Thus, the DTD-OMI strategy can provide extremely high imprinting efficiency. The charged head group of the imprinting template functioned only as an anchor to dock the imprinting template onto the mesopore template. If no functional monomer is used for interacting with the head group, the prepared molecularly imprinted mesoporous materials can not only recognize their imprinting template but also their head group-deleted analogues. The affinity and selectivity of MIPs arise not only from the imprinted cavities but also from the cumulative effect of individually interactions between the functional groups and target molecules. Considering this, the molar ratio of APBA-GPTES to TEOS was optimized and evaluated in terms of the imprinting factor (IF). First, in the optimization procedure, the molar ratio of the template molecule to APBA-GPTES was fixed at 1 : 1 and was not optimized, because the binding between the template and APBA-GPTES follows a 1 : 1 stoichiometry. Then, the molar
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ratio of APBA-GPTES to TEOS was investigated. The obtained MIPs exhibited gradually reduced AMP adsorption within the APBA-GPTES/TEOS molar ratio range from 1 : 9 to 0.1 : 9.9, while the NIPs showed gradually reduced AMP adsorption from 1 : 9 to 0.4 : 9.6 but a dramatic drop in AMP adsorption when the ratio exceeded 0.4 : 9.6. The best APBA-GPTES/TEOS molar ratio was found to be 0.2 : 9.8, which gave an IF value of 25.3 (Fig. S4, ESI†). To enhance the functionality complementary to the imprinted cavities toward the imprinting template, we further introduced APTES, which can provide hydrogen binding. When APTES of an equivalent molar ratio to APBA-GPTES was added, the performance of the resulting MIP was effectively improved. Particularly, the IF value dramatically increased to 43.0, which is outstanding in molecular imprinting. Besides, the binding constant was reduced by 2.6-fold (Fig. S5B and S10B, ESI†). Moreover, the cross-reactivity was reduced from 10–72% (Fig. S6, ESI†) to 2–23% (see the following text). Fig. 1 shows the transmission electron microscopic (TEM) image, X-ray diffraction (XRD) pattern, N2 adsorption–desorption isotherms and pore size distribution of AMP-imprinted MSNs. The mesoporous structure was confirmed by the TEM image and the XRD pattern. The pore diameter was measured to be 2.3 nm while the BET surface area was 833 m2 g 1, which obeyed the typical features of mesoporous materials. There were no discernible differences in the pore size of the imprinted and non-imprinted materials (Fig. 1D, Fig. S9D and Table S2, ESI†). The presence of amino and phenylboronic acid groups was confirmed by FT-IR (Fig. S11, ESI†). The peak in the XRD pattern of non-imprinted MSNs was slightly sharper and more intense than that of imprinted MSNs (Fig. 2B and Fig. S8B, ESI†). This is attributed to the larger precursor for imprinting (complexes composed of appended triethoxysilanes and the template) according to the rationalization for similar results in previous reports.14 To investigate the specificity of the imprinted MSNs prepared by DTD-OMI, a series of analogues of AMP and adenosine, including DA, guanosine, cytidine, uridine, GMP, CMP, DAMP and UMP, were used as interferents. As shown in Fig. 2, the AMPimprinted MSNs prepared by the DTD-OMI method exhibited
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Fig. 1 (A) TEM image, (B) XRD pattern, (C) N2 adsorption–desorption isotherms, and (D) pore size distribution for AMP-imprinted MSNs prepared by DTD-OMI.
Fig. 2 Selectivity of (A) AMP-imprinted MSNs by DTD-OMI and (B) adenosine-imprinted MSNs by bulk imprinting toward the template and its analogues. Hollow bar: imprinted MSNs; solid bar: non-imprinted MSNs.
apparently higher affinity toward the template AMP and the dummy template adenosine as compared with the affinity toward all the interferents. The cross-reactivity (Table S1, ESI†) toward the interferents was calculated to be 2–23%, which is well acceptable for the imprinting of small molecules.16 We comprehensively compared the performance of the DTDOMI strategy and bulk imprinting. The bulk imprinting method used herein was otherwise identical to the DTD-OMI approach except that AMP was replaced by adenosine so that no template– template docking was formed and the imprinting occurred in random directions. The adenosine-imprinted MSNs prepared by bulk imprinting exhibited rather poor specificity, with crossreactivity ranging from 10 to 72% (most higher than 60%, see Table S1, ESI† for details). Table 1 compares the performance of DTD-OMI and bulk imprinting. Although the binding constants toward the templates of these two kinds of molecularly imprinted
Table 1
MSNs were basically the same (the dissociation constants were about 10 4 M), a dramatic difference is that DTD-OMI provided much higher imprinting efficiency, template usage efficiency, imprinting factor and binding capacity. The imprinting efficiency was also much higher than the literature values for AMPimprinted MIPs (34.7–40%).17 Imprinting efficiency and template usage efficiency are two important criteria for the evaluation of a molecular imprinting approach. Imprinting efficiency is defined as the ratio of the number of imprinted cavities of the molecularly imprinted MSNs over the total number of template molecules used in the synthetic procedure, while template usage efficiency is the percentage of the amount of recovered template over the amount of template used. The former reflects the portion of well-formed binding cavities among all template molecules used, while the latter indicates the recovery of the template. Clearly, the DTD-OMI strategy is greatly favourable for imprints that are rare or hard to obtain. The feasibility of the imprinted MSNs for real-world applications was demonstrated with the specific enrichment of adenosine from human urine. Urinary ribonucleosides are potential biomarkers for early cancer diagnosis.18 A human urine sample from a healthy individual was extracted with AMP-imprinted MSNs by DTD-OMI and adenosine-imprinted MSNs by bulk imprinting. The extracted compounds were eluted with an acidic solution and the resulting solutions were subject to micellar electrokinetic chromatographic (MEKC) analysis. MEKC of unextracted urine sample was also performed for comparison. As shown in Fig. 3, the extracted sample exhibited a totally different profile as compared with the unextracted sample. When adenosine-imprinted MSNs were used as the sorbent, a small peak for adenosine along with five intense peaks was observed,
Fig. 3 MEKC electropherograms for (a) unextracted urine sample, (b) extracted by adenosine-imprinted MSNs prepared by bulk imprinting, (c) extracted by AMP-imprinted MSNs by DTD-OMI, (d) adenosine standard solution (0.1 mg mL 1), and (e) blank. The system peak was marked with an asterisk.
Comparison of the performance of DTD-OMI and bulk imprinting
Imprinting strategy
Test molecule
Imprinting efficiency (%)
Template usage efficiency (%)
Imprinting factor
Binding capacity (mmol g 1)
Dissociation constant (mM)
DTD-OMI DTD-OMI Bulk imprinting
AMP Adenosine Adenosine
(87.0 2.1)
(93.2 5.3)
(26.5 3.7)
(33.1 1.6)
43.0 6.2 43.6 2.9 7.9 1.2
187.1 7.5 191.7 9.2 72.7 9.9
103.8 6.6 111.3 7.1 135.2 8.1
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which is attributed to the poor specificity of the imprinted MSNs. As a comparison, when AMP-imprinted MSNs were used as the sorbent, a significantly intense peak for adenosine and several minor peaks were observed. The significantly enriched adenosine and the greatly reduced sample matrix are favourable for further quantification and identification of adenosine. In summary, a new molecular imprinting strategy, termed as dual-template docking oriented imprinting, has been established to prepare molecularly imprinted mesoporous materials. As compared with bulk imprinting, DTD-OMI did not require additional steps but provided significantly improved performance and binding properties. It is facile and highly efficient. Moreover, it can be easily extended to other templating and imprinting systems, for not only molecular recognition but also other applications. Thus, this strategy opened up a new avenue for facile and efficient preparation of molecularly imprinted mesoporous materials. We gratefully acknowledge the financial support of the National Science Fund for Distinguished Young Scholars (No. 21425520) and the general grant (No. 21275073) from the National Natural Science Foundation of China to Z.L.
Notes and references 1 (a) G. Wulff and J. Q. Liu, Acc. Chem. Res., 2012, 45, 239–247; (b) S. Martha and D. A. Spivak, J. Am. Chem. Soc., 2004, 126, 7827–7833; (c) Y. Hoshino, H. Koide, T. Urakami, H. Kanazawa, T. Kodama, N. Oku and K. J. Shea, J. Am. Chem. Soc., 2010, 132, 6644–6645; (d) L. Ye and K. Mosbach, Chem. Mater., 2008, 20, 859–868; (e) G. Vlatakis, L. I. Andersson, R. Muller and K. Mosbach, Nature, 1993, 361, 645–647. 2 (a) P. T. Tanev, M. Chibwe and T. J. Pinnavaia, Nature, 1994, 368, 321–323; (b) A. Corma, Chem. Rev., 1997, 97, 2373–2419; (c) Y. Wan and D. Y. Zhao, Chem. Rev., 2007, 107, 2821–2860; (d) Y. W. Xu, Z. X. Wu, L. J. Zhang, H. J. Lu, P. Y. Yang, P. A. Webley and D. Y. Zhao, Anal. Chem., 2009, 81, 503–508; (e) R. J. Tian, H. Zhang, M. L. Ye, X. G. Jiang, L. H. Hu, X. Li, X. H. Bao and H. F. Zou, Angew. Chem., Int. Ed., 2007, 46, 962–965; ( f ) H. Q. Qin, P. Gao, F. J. Wang, L. Zhao, J. Zhu, A. Q. Wang, T. Zhang, R. A. Wu and H. F. Zou, Angew. Chem., Int. Ed., 2011, 50, 12218–12221. 3 (a) A. G. Strikovsky, D. Kasper, M. Grun, B. S. Green, J. Hradil and G. Wulff, J. Am. Chem. Soc., 2000, 122, 6295–6296; (b) A. Katz and M. E. Davis, Nature, 2000, 403, 286–289.
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Cite this: DOI: 10.1039/c5cc03207e Received 17th April 2015, Accepted 26th May 2015
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Dual-template docking oriented molecular imprinting: a facile strategy for highly efficient imprinting within mesoporous materials† Yang Chen, Xinglin Li, Danyang Yin, Daojin Li, Zijun Bie and Zhen Liu*
DOI: 10.1039/c5cc03207e www.rsc.org/chemcomm
We present a new strategy, called dual-template docking oriented molecular imprinting (DTD-OMI), for facile and highly efficient imprinting within mesoporous materials. As compared with bulk imprinting, which is a widely used strategy, DTD-OMI did not require additional steps, but provided significantly improved imprinting efficiency and binding properties.
Molecularly imprinted polymers (MIPs) and mesoporous materials are both important advanced materials. MIPs, as synthetic receptors with antibody-like binding properties or enzyme-like catalytic activities, have been used as biomimetic materials in important applications ranging from sensing to separation to catalysis.1 Mesoporous materials, which possess highly ordered mesopores, have also gained enormous attention in catalysis, sensing and separation.2 Clearly, a combination of these two types of advanced materials will be highly desirable for prospective important applications due to the merits from both sides, particularly high specificity, high capacity and size-sieving effect. However, molecular imprinting within mesoporous materials is a challenging task. Although a large variety of imprinting strategies or approaches have been proposed, such as bulk imprinting,3 surface imprinting,4 oriented imprinting,5 epitope imprinting,6 Pickering emulsion imprinting,7 metal coordination,8 hierarchical imprinting,9 nanofabrication,10 and boronate affinity-based molecular imprinting,11 all these methods cannot be directly applied to molecular imprinting within mesoporous materials, because imprint molecules must be imprinted on the surface of mesopores. To fill the gap, three main approaches have been developed so far: (1) grafted surface imprinting,12 in which base mesoporous silica is first prepared and then surface imprinting was carried out to fabricate a thin imprinting layer onto the wall of the mesopores; (2) surface imprint-based dummy imprinting,13 in which an imprint-like surfactant was mixed with the mesopore-forming State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, 22 Hankou Road, Nanjing 210093, China. E-mail: [email protected]; Fax: +86-25-8368-5639 † Electronic supplementary information (ESI) available. See DOI: 10.1039/c5cc03207e
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micelles so that the imprint was directly imprinted in the wall of mesopores; and (3) covalent bulk imprinting,14 in which a specially synthesized crosslinker that contains an imprint was used to form mesoporous silica and the imprint was removed by heating. However, these methods are associated with some drawbacks. For instance, all these methods required additional steps. More importantly, the efficiency of these methods has not been well investigated yet. Therefore, straightforward and efficient imprinting strategies or approaches are highly desirable. Herein we proposed a facile strategy, called dual-template docking oriented molecular imprinting (DTD-OMI), for highly efficient imprinting within mesoporous materials. The central concept of this strategy relied on two keys: (1) the template– template docking, and (2) oriented imprinting. This strategy is as simple as the procedure for preparing regular mesoporous materials. Meanwhile, it can provide high imprinting efficiency and highly desirable binding properties. Although this strategy is designed for the imprinting of charged targets, MIPs specific to uncharged target molecules can also be prepared using a charged analogue of the target as the imprint (dummy molecular imprinting). In this study, the benefits of DTD-OMI over other imprinting strategies particularly bulk imprinting as well as its feasibility for dummy molecular imprinting were well demonstrated. Feasibility for application to real samples was verified with the specific enrichment of adenosine from human urine by adenosine monophosphate (AMP)-imprinted MSNs. The DTD-OMI strategy can be expanded to other mesopore templates and imprinting templates. Thus, it opened up a new avenue to the facile and efficient synthesis of molecularly imprinted mesoporous materials. As a proof-of-principle, AMP-imprinted MCM-41 mesoporous silica nanoparticles (MSNs) were prepared in this study. The principle and procedure are illustrated in Scheme 1. Cetyltrimethylammonium bromide (CTAB) was used as a mesopore template. Rod-like CTAB micelles, which possess positive charges at the surface, were first formed. AMP, a negatively charged compound, was used as an imprint and added to the solution. Due to electrostatic attraction, the imprint molecules
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Scheme 1
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Schematic diagram of the DTD-OMI strategy.
were docked onto the surface of the CTAB micelles to form dual-template complexes. After that, an appropriate Si source precursor, a mixture containing tetraethoxysilane (TEOS), 3-aminopropyl triethoxysilane (APTES) and 3-aminophenylboronic acid appended 3-glycidyloxypropyl triethoxysilane (APBA-GPTES) in this study, was added to the solution. The precursor APBA-GPTES was produced from the reaction of a 1 : 1 stoichiometric mixture of APBA and GPTES (see more details in the ESI†). The co-condensation occurred around the dual-template complexes. Due to the template–template docking configuration, other functionalities of the template, including the ribose and adenine moieties, can interact with the functional monomers APBA-GPTES and APTES due to boronate affinity and hydrogen bonding, respectively (see Fig. S3, ESI† for details). Therefore, all the imprint molecules were imprinted in the wall of the mesopores with access to the mesopore template. After imprinting, by using Soxhlet extraction with a strong acidic solution, which is a regular template removal procedure for the preparation of MSNs, both the mesopore template and the imprinting template were efficiently removed simultaneously, because the covalent boronate affinity bonding can be disrupted under acidic conditions.15 Thus, the DTD-OMI strategy can provide extremely high imprinting efficiency. The charged head group of the imprinting template functioned only as an anchor to dock the imprinting template onto the mesopore template. If no functional monomer is used for interacting with the head group, the prepared molecularly imprinted mesoporous materials can not only recognize their imprinting template but also their head group-deleted analogues. The affinity and selectivity of MIPs arise not only from the imprinted cavities but also from the cumulative effect of individually interactions between the functional groups and target molecules. Considering this, the molar ratio of APBA-GPTES to TEOS was optimized and evaluated in terms of the imprinting factor (IF). First, in the optimization procedure, the molar ratio of the template molecule to APBA-GPTES was fixed at 1 : 1 and was not optimized, because the binding between the template and APBA-GPTES follows a 1 : 1 stoichiometry. Then, the molar
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ratio of APBA-GPTES to TEOS was investigated. The obtained MIPs exhibited gradually reduced AMP adsorption within the APBA-GPTES/TEOS molar ratio range from 1 : 9 to 0.1 : 9.9, while the NIPs showed gradually reduced AMP adsorption from 1 : 9 to 0.4 : 9.6 but a dramatic drop in AMP adsorption when the ratio exceeded 0.4 : 9.6. The best APBA-GPTES/TEOS molar ratio was found to be 0.2 : 9.8, which gave an IF value of 25.3 (Fig. S4, ESI†). To enhance the functionality complementary to the imprinted cavities toward the imprinting template, we further introduced APTES, which can provide hydrogen binding. When APTES of an equivalent molar ratio to APBA-GPTES was added, the performance of the resulting MIP was effectively improved. Particularly, the IF value dramatically increased to 43.0, which is outstanding in molecular imprinting. Besides, the binding constant was reduced by 2.6-fold (Fig. S5B and S10B, ESI†). Moreover, the cross-reactivity was reduced from 10–72% (Fig. S6, ESI†) to 2–23% (see the following text). Fig. 1 shows the transmission electron microscopic (TEM) image, X-ray diffraction (XRD) pattern, N2 adsorption–desorption isotherms and pore size distribution of AMP-imprinted MSNs. The mesoporous structure was confirmed by the TEM image and the XRD pattern. The pore diameter was measured to be 2.3 nm while the BET surface area was 833 m2 g 1, which obeyed the typical features of mesoporous materials. There were no discernible differences in the pore size of the imprinted and non-imprinted materials (Fig. 1D, Fig. S9D and Table S2, ESI†). The presence of amino and phenylboronic acid groups was confirmed by FT-IR (Fig. S11, ESI†). The peak in the XRD pattern of non-imprinted MSNs was slightly sharper and more intense than that of imprinted MSNs (Fig. 2B and Fig. S8B, ESI†). This is attributed to the larger precursor for imprinting (complexes composed of appended triethoxysilanes and the template) according to the rationalization for similar results in previous reports.14 To investigate the specificity of the imprinted MSNs prepared by DTD-OMI, a series of analogues of AMP and adenosine, including DA, guanosine, cytidine, uridine, GMP, CMP, DAMP and UMP, were used as interferents. As shown in Fig. 2, the AMPimprinted MSNs prepared by the DTD-OMI method exhibited
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Fig. 1 (A) TEM image, (B) XRD pattern, (C) N2 adsorption–desorption isotherms, and (D) pore size distribution for AMP-imprinted MSNs prepared by DTD-OMI.
Fig. 2 Selectivity of (A) AMP-imprinted MSNs by DTD-OMI and (B) adenosine-imprinted MSNs by bulk imprinting toward the template and its analogues. Hollow bar: imprinted MSNs; solid bar: non-imprinted MSNs.
apparently higher affinity toward the template AMP and the dummy template adenosine as compared with the affinity toward all the interferents. The cross-reactivity (Table S1, ESI†) toward the interferents was calculated to be 2–23%, which is well acceptable for the imprinting of small molecules.16 We comprehensively compared the performance of the DTDOMI strategy and bulk imprinting. The bulk imprinting method used herein was otherwise identical to the DTD-OMI approach except that AMP was replaced by adenosine so that no template– template docking was formed and the imprinting occurred in random directions. The adenosine-imprinted MSNs prepared by bulk imprinting exhibited rather poor specificity, with crossreactivity ranging from 10 to 72% (most higher than 60%, see Table S1, ESI† for details). Table 1 compares the performance of DTD-OMI and bulk imprinting. Although the binding constants toward the templates of these two kinds of molecularly imprinted
Table 1
MSNs were basically the same (the dissociation constants were about 10 4 M), a dramatic difference is that DTD-OMI provided much higher imprinting efficiency, template usage efficiency, imprinting factor and binding capacity. The imprinting efficiency was also much higher than the literature values for AMPimprinted MIPs (34.7–40%).17 Imprinting efficiency and template usage efficiency are two important criteria for the evaluation of a molecular imprinting approach. Imprinting efficiency is defined as the ratio of the number of imprinted cavities of the molecularly imprinted MSNs over the total number of template molecules used in the synthetic procedure, while template usage efficiency is the percentage of the amount of recovered template over the amount of template used. The former reflects the portion of well-formed binding cavities among all template molecules used, while the latter indicates the recovery of the template. Clearly, the DTD-OMI strategy is greatly favourable for imprints that are rare or hard to obtain. The feasibility of the imprinted MSNs for real-world applications was demonstrated with the specific enrichment of adenosine from human urine. Urinary ribonucleosides are potential biomarkers for early cancer diagnosis.18 A human urine sample from a healthy individual was extracted with AMP-imprinted MSNs by DTD-OMI and adenosine-imprinted MSNs by bulk imprinting. The extracted compounds were eluted with an acidic solution and the resulting solutions were subject to micellar electrokinetic chromatographic (MEKC) analysis. MEKC of unextracted urine sample was also performed for comparison. As shown in Fig. 3, the extracted sample exhibited a totally different profile as compared with the unextracted sample. When adenosine-imprinted MSNs were used as the sorbent, a small peak for adenosine along with five intense peaks was observed,
Fig. 3 MEKC electropherograms for (a) unextracted urine sample, (b) extracted by adenosine-imprinted MSNs prepared by bulk imprinting, (c) extracted by AMP-imprinted MSNs by DTD-OMI, (d) adenosine standard solution (0.1 mg mL 1), and (e) blank. The system peak was marked with an asterisk.
Comparison of the performance of DTD-OMI and bulk imprinting
Imprinting strategy
Test molecule
Imprinting efficiency (%)
Template usage efficiency (%)
Imprinting factor
Binding capacity (mmol g 1)
Dissociation constant (mM)
DTD-OMI DTD-OMI Bulk imprinting
AMP Adenosine Adenosine
(87.0 2.1)
(93.2 5.3)
(26.5 3.7)
(33.1 1.6)
43.0 6.2 43.6 2.9 7.9 1.2
187.1 7.5 191.7 9.2 72.7 9.9
103.8 6.6 111.3 7.1 135.2 8.1
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which is attributed to the poor specificity of the imprinted MSNs. As a comparison, when AMP-imprinted MSNs were used as the sorbent, a significantly intense peak for adenosine and several minor peaks were observed. The significantly enriched adenosine and the greatly reduced sample matrix are favourable for further quantification and identification of adenosine. In summary, a new molecular imprinting strategy, termed as dual-template docking oriented imprinting, has been established to prepare molecularly imprinted mesoporous materials. As compared with bulk imprinting, DTD-OMI did not require additional steps but provided significantly improved performance and binding properties. It is facile and highly efficient. Moreover, it can be easily extended to other templating and imprinting systems, for not only molecular recognition but also other applications. Thus, this strategy opened up a new avenue for facile and efficient preparation of molecularly imprinted mesoporous materials. We gratefully acknowledge the financial support of the National Science Fund for Distinguished Young Scholars (No. 21425520) and the general grant (No. 21275073) from the National Natural Science Foundation of China to Z.L.
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