Molecular Imprinting: A Versatile Tool for Separation, Sensors and Catalysis

  • Wuke Li
  • Songjun LiEmail author
Part of the Advances in Polymer Science book series (POLYMER, volume 206)


Molecular imprinting is a promising technique for the preparation of polymers with predeterminedselectivity and high affinity. Normally, based on the self-assembly of functional monomers and templates(i.e., imprint molecules), the imprinted polymers are produced by crosslinking polymerizations. The templatesare subsequently removed from the polymer, leaving behind binding sites complementary to the imprint speciesin terms of the shape and the position of functional groups. Recognition of the polymer constitutes aninduced molecular memory, which makes the binding sites capable of selectively recognizing the imprint species.This article presents a limited review on molecular self-assembly and the uses of these imprinted polymersin separation, sensors, and catalysis. Other aspects including related backgrounds are also discussed.

Catalysis Molecular imprinting Self-assembly Sensor Separation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



The authors want to thank NSFC for presenting financial support to conduct this work (Granted No. 20603010). Thank also Professor Guangfu Yang for providing constructive suggestions in the revision process, which play an important role on improving this article.


  1. 1.
    Meng ZH, Sode K (2005) The molecular reaction vessels for a transesterification process created by molecular imprinting technique. J Mol Recogn 18(3):262–266 CrossRefGoogle Scholar
  2. 2.
    Takeuchi T, Mukawa T, Shinmori H (2005) Signaling molecularly imprinted polymers: molecular recognition-based sensing materials. Chem Record 5(5):263–275 CrossRefGoogle Scholar
  3. 3.
    Dickey FH (1949) The preparation of specific adsorbents. Proc Natl Acad Sci 35(5):227–229 CrossRefGoogle Scholar
  4. 4.
    Wulff G (1995) Molecular imprinting in cross-linking materials with the aid of molecular templates: a way towards artificial antibodies. Angew Chem Int Ed 34(17):1812–1832 CrossRefGoogle Scholar
  5. 5.
    Mosbach K, Ramstrom O (1996) The emerging technique of molecular imprinting and its future impact on biotechnology. Biotechnol 14(2):163–170 CrossRefGoogle Scholar
  6. 6.
    Pauling L, Campbell D (1942) The manufacture of antibodies in vitro. J Experimtl Med 76(2):211–220 CrossRefGoogle Scholar
  7. 7.
    Mosbach K (2001) Toward the next generation of molecular imprinting with emphasis on the formation, by direct molding, of compounds with biological activity (biomimetics). Anal Chim Act 435(1):3–8 CrossRefGoogle Scholar
  8. 8.
    Mosbach K, Yu Y, Andersch J, Ye L (2001) Generation of new enzyme inhibitors using imprinted binding sites: the anti-idiotypic approach, a step toward the next generation of molecular imprinting. J Am Chem Soc 123(49):12420–12421 CrossRefGoogle Scholar
  9. 9.
    Ye L, Mosbach K (2001) Molecularly imprinted microspheres as antibody binding mimics. React Funct Polym 48(2):149–157 CrossRefGoogle Scholar
  10. 10.
    El-ghayoury A, Hofmeier H, de Ruiter B, Schubert US (2003) Combining covalent and noncovalent cross-linking: a novel terpolymer for two-step curing applications. Macromolecules 36(11):3955–3959 CrossRefGoogle Scholar
  11. 11.
    Whitcombe MJ (2006) MIP catalysts – from theory to practice. In: Piletsky S, Turner A (eds) Molecular imprinting of polymers. Landes Bioscience 83–108 Google Scholar
  12. 12.
    Shiomi T, Matsui M, Mizukami F, Sakaguchi K (2005) A method for the molecular imprinting of hemoglobin on silica surfaces using silanes. Biomaterials 26(27):5564–5571 CrossRefGoogle Scholar
  13. 13.
    Klein JU, Whitcombe MJ, Mulholland F, Vulfson EN (1999) Template-mediated synthesis of a polymeric receptor specific to amino acid sequences. Angew Chem Int Ed 38(13):2057–2060 CrossRefGoogle Scholar
  14. 14.
    Fish WP, Ferreira J, Sheardy RD, Snow NH, O'Brien TP (2005) Rational design of an imprinted polymer: maximizing selectivity by optimizing the monomer-template ratio for a cinchonidine MIP, prior to polymerization, using microcalorimetry. J Liquid Chromatogr. Related Technol 28(1):1–15 CrossRefGoogle Scholar
  15. 15.
    Svenson J, Ning Z, Fohrman U, Nicholls IA (2005) The role of functional monomer-template complexation on the performance of atrazine molecularly imprinted polymers. Anal Lett 38(1):57–69 CrossRefGoogle Scholar
  16. 16.
    Svenson J, Andersson HS, Piletsky SA, Nicholls IA (1998) Spectroscopic studies of the molecular imprinting self assembly process. J Mol Recogn 11(1):83–86 CrossRefGoogle Scholar
  17. 17.
    Andersson HS, Nicholls IA (1997) Spectroscopic evaluation of molecular imprinting polymerization systems. Bioorg Chem 25(3):203–211 CrossRefGoogle Scholar
  18. 18.
    Li Z, Day M, Ding J, Faid K (2005) Synthesis and characterization of functional methacrylate copolymers and their application in molecular imprinting. Macromolecules 38(7):2620–2625 CrossRefGoogle Scholar
  19. 19.
    Kim TH, Ki CD, Cho H, Chang T, Chang JY (2005) Facile preparation of core-shell type molecularly imprinted particles: molecular imprinting into aromatic polyimide coated on silica spheres. Macromolecules 38(15):6423–6428 CrossRefGoogle Scholar
  20. 20.
    Ou JJ, Tang SW, Zou HF (2005) Chiral separation of 1,1′-bi-2-naphthol and its analogue on molecular imprinting monolithic columns by HPLC. J Separat Sci 28(17):2282–2287 CrossRefGoogle Scholar
  21. 21.
    Turiel E, Martin-Esteban A (2005) Molecular imprinting technology in capillary electrochromatography. J Separat Sci 28(8):719–728 CrossRefGoogle Scholar
  22. 22.
    Kim H, Guiochon G (2005) Thermodynamic studies on the solvent effects in chromatography on molecularly imprinted polymers. 1. Nature of the organic modifier. Anal Chem 77(6):1708–1717 CrossRefGoogle Scholar
  23. 23.
    Sellergren B (2001) Imprinted chiral stationary phases in high-performance liquid chromatography. J Chromatogr A 906(1):227–252 CrossRefGoogle Scholar
  24. 24.
    Sellergren B, Lepistoe M, Mosbach K (1988) Highly enantioselective and substrate-selective polymers obtained by molecular imprinting utilizing noncovalent interactions. NMR and chromatographic studies on the nature of recognition. J Am Chem Soc 110(17):5853–5860 CrossRefGoogle Scholar
  25. 25.
    Sellergren B (1989) Molecular imprinting by noncovalent interactions: tailor-made chiral stationary phases of high selectivity and sample load capacity. Chirality 1(1):63–68 CrossRefGoogle Scholar
  26. 26.
    Sellergren B (1997) Noncovalent molecular imprinting: antibody-like molecular recognition in polymeric network materials. Trends Anal Chem 16(6):310–320 CrossRefGoogle Scholar
  27. 27.
    Huang X, Kong L, Li X, Zheng C, Zou H (2003) Molecular imprinting of nitrophenol and hydroxybenzoic acid isomers: effect of molecular structure and acidity on imprinting. J Mol Recogn 16(6):406–411 CrossRefGoogle Scholar
  28. 28.
    Allender CJ, Brain KR, Heard CM (1997) Binding cross-reactivity of Boc-phenylalanine enantiomers on molecularly imprinted polymers. Chirality 9(3):233–237 CrossRefGoogle Scholar
  29. 29.
    Fischer L, Mueller R, Ekberg B, Mosbach K (1991) Direct enantioseparation of beta-adrenergic blockers using a chiral stationary phase prepared by molecular imprinting. J Am Chem Soc 113(24):9358–9360 CrossRefGoogle Scholar
  30. 30.
    Andersson HS, Koch-Schmidt AC, Ohlson S, Mosbach K (1996) Study of the nature of recognition in molecularly imprinted polymers. J Mol Recogn 9(6):675–682 CrossRefGoogle Scholar
  31. 31.
    Lin JM, Nakagama T, Uchiyama K, Hobo T (1998) Temperature effect on chiral recognition of some amino acids with molecularly imprinted polymer filled capillary electrochromatography. Biomed Chromatogr 11(5):298–302 CrossRefGoogle Scholar
  32. 32.
    Li ZW, Yang GL, Wang DX, Zhou SL, Liu ED, Chen Y (2003) Separation of aminoantipyrine and its close analogues by molecular imprinting stationary phase. Chem J Internet 5(6):46 Google Scholar
  33. 33.
    Gavioli E, Maier NM, Haupt K, Mosbach K, Lindner W (2005) Analyte templating: enhancing the enantioselectivity of chiral selectors upon incorporation into organic polymer environments. Anal Chem 77(15):5009–5018 CrossRefGoogle Scholar
  34. 34.
    Ramstrom O, Nicholls IA, Mosbach K (1994) Synthetic peptide receptor mimics: highly stereoselective recognition in nonconvalent molecularly imprinted polymers. Tetrahedron: Assymetry 5(4):649–656 CrossRefGoogle Scholar
  35. 35.
    Mayes AG, Andersson L, Mosbach K (1994) Sugar binding polymers showing high anomeric and epimeric discrimination by noncovalent molecular imprinting. Anal Biochem 222(2):483–488 CrossRefGoogle Scholar
  36. 36.
    Li P, Rong F, Xie YB, Hu V, Yuan CW (2004) Study on the binding characteristic of S-naproxen imprinted polymer and the interactions between templates and monomers. J Anal Chem 59(10):939–944 CrossRefGoogle Scholar
  37. 37.
    Donato L, Figoli A, Drioli E (2005) Novel composite poly (4-vinylpyridine)/polypropylene membranes with recognition properties for (S)-naproxen. J Pharm Biomed Anal 37(5):1003–1008 CrossRefGoogle Scholar
  38. 38.
    Kempe M, Mosbach K (1994) Direct resolution of naproxen on a non-covalently molecularly imprinted chiral stationary phase. J Chromatogr A 664(2):276–279 CrossRefGoogle Scholar
  39. 39.
    Arnold FH, Plunkett SD, Vidyasankar S (1994) Template polymerization using metal ion coordination: metal replacement to optimize templating and substrate re-binding. Polym Preprints 35(9):996–997 Google Scholar
  40. 40.
    Uezu K, Yoshida M, Goto M, Furusaki S (1999) Molecular recognition using surface template polymerization. Chemtech 29(4):12–18 Google Scholar
  41. 41.
    Gong SL, Yu ZJ, Meng LZ, Hu L, He YB (2004) Dye-molecular-imprinted polysiloxanes. II. Preparation, characterization, and recognition behavior. J Appl Polym Sci 93(2):637–643 CrossRefGoogle Scholar
  42. 42.
    Dobashi A, Nishida S, Kurata K, Hamada M (2002) Chiral separation of enantiomeric 1,2-diamines using molecular imprinting method and selectivity enhancement by addition of achiral primary amines into eluents. Anal Sci 18(1):32–35 CrossRefGoogle Scholar
  43. 43.
    Chen ZD, Nagaoka T (2000) Recognition of vitamin K1 with a molecularly imprinted self-assembled monolayer film. Bunsekikagaku, 49(7):543–546 Google Scholar
  44. 44.
    Bitz GG, Schmid MG (2001) Chiral separation by chromatographic and electromigration techniques. Biopharm Drug Dispos 22(7):291–336 CrossRefGoogle Scholar
  45. 45.
    Cai LS, Wu CY, Mei SR, Zeng ZR (2004) Molecularly imprinted polymer theophylline retention and molecular recognition properties in capillary electrochromatography. Wuhan Univ J Natl Sci 9(3):359–365 CrossRefGoogle Scholar
  46. 46.
    Alvarez-Lorenzo C, Concheiro A (2003) Effects of surfactants on gel behavior: design implications for drug delivery systems. Am J Drug Deliv 1(2):77–101 CrossRefGoogle Scholar
  47. 47.
    Sellergren B, Buchel G (2005) Porous, molecularly imprinted polymer and a process for the preparation thereof. US Patent 6,881,804 (B1), Apr. 19, Pages 11 Google Scholar
  48. 48.
    Vallano PT, Remcho VT (2000) Highly selective separations by capillary electrochromatography: molecular imprint polymer sorbents. J Chromatogr A 887(2):125–135 CrossRefGoogle Scholar
  49. 49.
    Sellergren B (1994) Imprinted dispersion polymers: a new class of easily accessible affinity stationary phases. J Chromatogr A 673(1):133–141 CrossRefGoogle Scholar
  50. 50.
    Kim K, Kim D (2005) High-performance liquid chromatography separation characteristics of molecular-imprinted poly(methacrylic acid) microparticles prepared by suspension polymerization. J Appl Polym Sci 96(1):200–212 CrossRefGoogle Scholar
  51. 51.
    Ho KC, Yeh WM, Tung TS, Liao JY (2005) Amperometric detection of morphine based on poly(3,4-ethylene dioxythiophene) immobilized molecularly imprinted polymer particles prepared by precipitation polymerization. Anal Chim Act 542(1):90–96 CrossRefGoogle Scholar
  52. 52.
    Say R, Erdem M, Ersoz A, Turk H, Denizli A (2005) Biomimetic catalysis of an organophosphate by molecularly surface imprinted polymers. Appl Catal A 286(2):221–225 CrossRefGoogle Scholar
  53. 53.
    Piscopo L, Prandi C, Coppa M, Sparnacci K, Laus M, Lagana A, Curini R, D'Ascenzo G (2002) Uniformly sized molecularly imprinted polymers (MIPs) for 17β-estradiol. Macromol Chem Phys 203(10):1532–1538 CrossRefGoogle Scholar
  54. 54.
    Schweitz L, Spegel P, Nilsson S (2001) Approaches to molecular imprinting based selectivity in capillary electrochromatography. Electrophoresis 22(19):4053–4063 CrossRefGoogle Scholar
  55. 55.
    Dickert FL, Lieberzeit P, Tortschanoff M (2000) Molecular imprints as artificial antibodies – a new generation of chemical sensors. Sensors Actuators B 65(2):186–189 CrossRefGoogle Scholar
  56. 56.
    Gao SH, Wang W, Wang BH (2001) Building fluorescent sensors for carbohydrates using template-directed polymerizations. Bioorg Chem 29(5):308–320 CrossRefGoogle Scholar
  57. 57.
    Liang CD, Peng H, Zhou AH, Nie LH, Yao SZ (2000) Molecular imprinting polymer coated BAW bio-mimic sensor for direct determination of epinephrine. Anal Chim Act 415(2):135–141 CrossRefGoogle Scholar
  58. 58.
    Piletsky SA, Panasyuk TL, Piletskaya EV, El'skaya AV, Levi R, Karube I, Wulff G (1998) Imprinted membranes for sensor technology: opposite behavior of covalently and noncovalently imprinted membranes. Macromolecules 31(7):2137–2140 CrossRefGoogle Scholar
  59. 59.
    Piletsky SA, Butovich IA, Kukhar VP (1992) Design of molecular sensors on the basis of substrate-selective polymer membranes. Zh Anal Khim 47(9):1681–1684 Google Scholar
  60. 60.
    Zhou YX, Yu B, Levon K (2003) Potentiometric sensing of chiral amino acids. Chem Mater 15(14):2774–2779 CrossRefGoogle Scholar
  61. 61.
    Shoji R, Takeuchi T, Kubo I (2003) Atrazine sensor based on molecularly imprinted polymer-modified gold electrode. Anal Chem 75(18):4882–4886 CrossRefGoogle Scholar
  62. 62.
    Ye L, Mosbach K (2001) Polymers recognizing biomolecules based on a combination of molecular imprinting and proximity scintillation: a new sensor concept. J Am Chem Soc 123(12):2901–2902 CrossRefGoogle Scholar
  63. 63.
    Chou LCS, Liu CC (2005) Development of a molecular imprinting thick film electrochemical sensor for cholesterol detection. Sensors Actuators B 110(2):204–208 CrossRefGoogle Scholar
  64. 64.
    Mosbach K, Haupt K (1998) Some new developments and challenges in non-covalent molecular imprinting technology. J Mol Recogn 11(1):62–68 CrossRefGoogle Scholar
  65. 65.
    Levi R, McNiven S, Piletsky SA, Rachkov A, Cheong SH, Yano K, Karube I (1997) Optical detection of chloramphenicol using molecularly imprinted polymers. Anal Chem 69(11):2017–2021 CrossRefGoogle Scholar
  66. 66.
    McNiven S, Kato M, Yano K, Karube I (1998) Chloramphenicol sensor based on an in situ imprinted polymer. Anal Chim Act 365(6):69–74 CrossRefGoogle Scholar
  67. 67.
    Piletsky SA, Piletskaya EV, Elgersma AV, Yano K, Parhometz YP, El'skaya AV, Karube I (1995) Atrazine sensing by molecularly imprinted membranes. Biosens Bioelectr 10(10):959–964 CrossRefGoogle Scholar
  68. 68.
    Yano K, Karube I (1999) Molecularly imprinted polymers for biosensor applications. Trends Anal Chem 18(3):1999–2004 CrossRefGoogle Scholar
  69. 69.
    Marx KA (2003) Quartz crystal microbalance: a useful tool for studying thin polymer films and complex biomolecular systems at the solution-surface interface. Biomacromolecules 4(5):1099–1120 CrossRefGoogle Scholar
  70. 70.
    Piletsky SA, Turner APF (2002) Electrochemical sensors based on molecularly imprinted polymers. Electroanalysis 14(5):317–323 CrossRefGoogle Scholar
  71. 71.
    Zeng YN, Zheng N, Osborne PG, Li YZ, Chang WB, Wen MJ (2002) Cyclic voltammetry characterization of metal complex imprinted polymer. J Mol Recogn 15(4):204–208 CrossRefGoogle Scholar
  72. 72.
    Zhou Y, Yu B, Shiu E, Levon K (2004) Potentiometric sensing of chemical warfare agents: surface imprinted polymer integrated with an indium tin oxide electrode. Anal Chem 76(10):2689–2693 CrossRefGoogle Scholar
  73. 73.
    Rich RL, Myszka DG (2005) Survey of the year 2004 commercial optical biosensor literature. J Mol Recogn 18(6):431–478 CrossRefGoogle Scholar
  74. 74.
    Liu JQ, Wulff G (2004) Functional mimicry of the active site of carboxypeptidase A by a molecular imprinting strategy: cooperativity of an amidinium and a copper ion in a transition-state imprinted cavity giving rise to high catalytic activity. J Am Chem Soc 126(24):7452–7453 CrossRefGoogle Scholar
  75. 75.
    Becker JJ, Gagne MR (2004) Exploiting the synergy between coordination chemistry and molecular imprinting in the quest for new catalysts. Acc Chem Res 37(10):798–804 CrossRefGoogle Scholar
  76. 76.
    Zimmerman SC, Zharov I, Wendland MS, Rakow NA, Suslick KS (2003) Molecular imprinting inside dendrimers. J Am Chem Soc 125(44):13504–13518 CrossRefGoogle Scholar
  77. 77.
    Slade CJ, Vulfson EN (1998) Induction of catalytic activity in proteins by lyophilization in the presence of a transition state analogue. Biotechnol Bioeng 57(2):211–215 CrossRefGoogle Scholar
  78. 78.
    Meng ZH, Yamazaki T, Sode K (2003) Enhancement of the catalytic activity of an artificial phosphotriesterase using a molecular imprinting technique. Biotechnol Lett 25(13):1075–1080 CrossRefGoogle Scholar
  79. 79.
    Beach IV, Shea KJ (1994) Designed catalysts. A synthetic network polymer that catalyzes the dehydrofluorhration of 4-fluoro-4-(p-nitrophenyl) butan-2-one. J Am Chem Soc 116(1):379–380 CrossRefGoogle Scholar
  80. 80.
    Muller R, Andersson LI, Mosbach K (1993) Molecularly imprinted polymers facilitating a beta-elimination reaction. Makromol. Chem Rapid Commun 14(10):637–641 CrossRefGoogle Scholar
  81. 81.
    Biffis A, Wulff G (2001) Molecular design of novel transition state analogues for molecular imprinting. New J Chem 25(12):1537–1542 CrossRefGoogle Scholar
  82. 82.
    Burri E, Ohm M, Daguenet C, Severin K (2005) Site-isolated porphyrin catalysts in imprinted polymers. Chem-A Euro J 11(17):5055–5061 CrossRefGoogle Scholar
  83. 83.
    Fireman-Shoresh S, Avnir D, Marx S (2003) General method for chiral imprinting of sol-gel thin films exhibiting enantioselectivity. Chem Mater 15(19):3607–3613 CrossRefGoogle Scholar
  84. 84.
    Visnjevski E, Yilmaz E, Bruggemanna O (2004) Catalyzing a cycloaddition with molecularly imprinted polymers obtained via immobilized templates. Appl Catal A 260(2):169–174 CrossRefGoogle Scholar
  85. 85.
    Yilmaz E, Haupt K, Mosbach K (2000) The use of immobilized templates – a new approach in molecular imprinting. Angew Chem Int Ed 39(12):2115–2118 CrossRefGoogle Scholar
  86. 86.
    Titirici MM, Hall AJ, Sellergren B (2002) Hierarchically imprinted stationary phases: mesoporous polymer beads containing surface-confined binding sites for adenine. Chem Mater 14(1):21–23 CrossRefGoogle Scholar
  87. 87.
    Nicholls IA, Rosengren JP (2002) Molecule selective surfaces. Bioseparat 10(3):301–305 Google Scholar
  88. 88.
    Sode K, Ohta S, Yanai Y, Yamazaki T (2003) Construction of a molecular imprinting catalyst using target analogue template and its application for an amperometric fructosylamine sensor. Biosens Bioelectr 18(12):1485–1490 CrossRefGoogle Scholar
  89. 89.
    Sode K, Ishimura Tsugawa FW (2001) Screening and characterization of fructosyl-valine utilizing marine microorganisms. Marine Biotechnol 3(2):126–132 CrossRefGoogle Scholar
  90. 90.
    Bruggemann O (2001) Chemical reaction engineering using molecularly imprinted polymeric catalysts. Anal Chim Act 435(11):197–207 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  1. 1.Key Laboratory of Pesticide & Chemical Biology of Ministry of EducationCollege of Chemistry, Central China Normal UniversityWuhanP.R. China

Personalised recommendations