Experimental Combinatorial Methods in Molecular Imprinting

  • Börje Sellergren
  • Eric Schillinger
  • Francesca Lanza
Part of the Integrated Analytical Systems book series (ANASYS)


Combinatorial techniques to synthesize and evaluate molecularly imprinted polymer sorbents for various molecular recognition based applications are reviewed. Various techniques to screen for binding and imprinting effects are discussed with reference to the application for which the sorbents are intended. State of the art high throughput synthesis techniques are outlined, and examples of how these have been used to identify suitable polymer building blocks or to optimize prepolymerization compositions to improve the molecular recognition properties in a given matrix are given.


Molecularly Imprint Polymer Itaconic Acid Functional Monomer Imprint Polymer Imprint Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Molecularly imprinted polymers. Man made mimics of antibodies and their applications in analytical chemistry; Sellergren, B., Ed.; Elsevier Science B.V.: Amsterdam, 2001; Vol. 23Google Scholar
  2. 2.
    Alexander, C.; Andersson, H. S.; Andersson, L. I.; Ansell, R. J.; Kirsch, N.; Nicholls, I. A.; O’Mahony, J.; Whitcombe, M. J., Molecular imprinting science and technology: A survey of the literature for the years up to and including 2003, J. Molec. Recogn. 2006, 19, 106–180CrossRefGoogle Scholar
  3. 3.
    Sellergren, B.; Lepistoe, M.; Mosbach, K., Highly enantioselective and substrate-selective polymers obtained by non-covalent interactions. NMR and chromatographic studies on the nature of recognition, J. Am. Chem. Soc. 1988, 110, 5853–5860CrossRefGoogle Scholar
  4. 4.
    Ellwanger, A.; Karlsson, L.; Owens, P. K.; Berggren, C.; Crecenzi, C.; Ensing, K.; Bayoudh, S.; Cormack, P.; Sherrington, D.; Sellergren, B., Evaluation of methods aimed at complete removal of template from molecularly imprinted polymers, Analyst 2001, 126, 784–792CrossRefGoogle Scholar
  5. 5.
    Takeuchi, T.; Fukuma, D.; Matsui, J., Combinatorial molecular imprinting: An approach to synthetic polymer receptors, Anal. Chem. 1999, 71, 285–290CrossRefGoogle Scholar
  6. 6.
    Lanza, F.; Sellergren, B., Method for synthesis and screening of large groups of molecularly imprinted polymers, Anal. Chem. 1999, 71, 2092–2096CrossRefGoogle Scholar
  7. 7.
    Cederfur, J.; Pei, Y.; Meng, Z.; Kempe, M., Synthesis and screening of a molecularly imprinted polymer library targeted for penicillin G, J. Combin. Chem. 2003, 5, 67–72CrossRefGoogle Scholar
  8. 8.
    Takeuchi, T.; Fukuma, D.; Matsui, J.; Mukawa, T., Combinatorial molecular imprinting for formation of atrazine decomposing polymers, Chem. Lett. 2001, 6, 530–531CrossRefGoogle Scholar
  9. 9.
    Davies, M. P.; De Biasi, V.; Perrett, D., Approaches to the rational design of molecularly imprinted polymers, Anal. Chim. Acta 2004, 504, 7–14CrossRefGoogle Scholar
  10. 10.
    Navarro-Villoslada, F.; San Vicente, B.; Moreno-Bondi, M. C., Application of multivariate analysis to the screening of molecularly imprinted polymers for bisphenole, Anal. Chim. Acta 2004, 504, 149–162CrossRefGoogle Scholar
  11. 11.
    Davidson, L.; Blencowe, A.; Drew, M. G. B.; Freebairn, K. W.; Hayes, W., Synthesis and evaluation of a solid supported molecular tweezer type receptor for cholesterol, J. Mater. Chem. 2003, 13, 758–766CrossRefGoogle Scholar
  12. 12.
    Piletsky, S. A.; Karim, K.; Piletska, E. V.; Day, C. J.; Freebairn, D. W.; Legge, C.; Turner, A. P. F., Recognition of ephedrine enantiomers by molecularly imprinted polymers designed using a computational approach, Analyst 2001, 126, 1826–1830CrossRefGoogle Scholar
  13. 13.
    Sellergren, B., Polymer- and template-related factors influencing the efficiency in molecularly imprinted solid-phase extractions, Trends Anal. Chem. 1999, 18, 164–174CrossRefGoogle Scholar
  14. 14.
    Sellergren, B.; Shea, K. J., On the influence of polymer morphology on the ability of imprinted polymers to separate enantiomers, J. Chromatogr. 1993, 635, 31CrossRefGoogle Scholar
  15. 15.
    Quaglia, M.; Chenon, K.; Hall, A. J.; De Lorenzi, E.; Sellergren, B., Target analogue imprinted polymers with affinity for folic acid and related compounds, J. Am. Chem. Soc. 2001, 123, 2146–2154CrossRefGoogle Scholar
  16. 16.
    Dirion, B.; Lanza, F.; Sellergren, B.; Chassaing, C.; Venn, R.; Berggren, C., Selective solid phase extraction of a drug lead compound using molecularly imprinted polymers prepared by the target analogue approach, Chromatographia 2002, 56, 237–241CrossRefGoogle Scholar
  17. 17.
    Andersson, L. I.; Paprica, A.; Arvidsson, T., A highly selective solid-phase extraction sorbent for preconcentration of sameridine made by molecular imprinting, Chromatographia 1997, 46, 57–62CrossRefGoogle Scholar
  18. 18.
    Dzygiel, P.; O’Donnell, E.; Fraier, D.; Chassaing, C.; Cormack, P. A. G., Evaluation of water-compatible molecularly imprinted polymers as solid-phase extraction sorbents for the selective extraction of sildenafil and its desmethyl metabolite from biological samples, J. Chromatogr. B 2007, 853(1–2), 346–353CrossRefGoogle Scholar
  19. 19.
    Köber, R.; Fleischer, C. T.; Lanza, F.; Boos, K.-S.; Sellergren, B.; Barcelo, D., Evaluation of a multidimensional solid phase extraction platform (six-spe) for highly selective on-line clean-up and high throughput lc-ms analysis of triazines in river water samples using molecularly imprinted polymers (mips), Anal. Chem. 2001, 73, 2437–2444CrossRefGoogle Scholar
  20. 20.
    Karlsson, J. G.; Andersson, L. I.; Nicholls, I. A., Probing the molecular basis for ligand-selective recognition in molecularly imprinted polymers selective for the local anesthetic bupivacaine, Anal. Chim. Acta 2001, 435, 57–64CrossRefGoogle Scholar
  21. 21.
    Manesiotis, P.; Hall, A. J.; Courtois, J.; Irgum, K.; Sellergren, B., An artificial riboflavin receptor prepared by a template analogue imprinting strategy, Angewandte Chemie, Intern. Ed. 2005, 44, 3902–3906CrossRefGoogle Scholar
  22. 22.
    Ramström, O.; Andersson, L. I.; Mosbach, K., Recognition sites incorporating both pyridinyl and carboxy functionalities prepared by molecular imprinting, J. Org. Chem. 1993, 58, 7562–7564CrossRefGoogle Scholar
  23. 23.
    Lübke, C.; Lübke, M.; Whitcombe, M. J.; Vulfson, E. N., Imprinted polymers prepared with stoichiometric template–monomer complexes: Efficient binding of ampicillin from aqueous solutions, Macromolecules 2000, 33, 5098–5105CrossRefGoogle Scholar
  24. 24.
    Dirion, B.; Cobb, Z.; Schillinger, E.; Andersson, L. I.; Sellergren, B., Water-compatible molecularly imprinted polymers obtained via high-throughput synthesis and experimental design, J. Amer. Chem. Soc. 2003, 125, 15101–15109CrossRefGoogle Scholar
  25. 25.
    Wulff, G.; Knorr, K., Stoichiometric imprinting, Bioseparation 2002, 10, 257CrossRefGoogle Scholar
  26. 26.
    Hall, A. J.; Manesiotis, P.; Emgenbroich, M.; Quaglia, M.; De Lorenzi, E.; Sellergren, B., Urea host monomers for stoichiometric molecular imprinting of oxyanions, J. Org. Chem. 2005, 70, 1732–1736CrossRefGoogle Scholar
  27. 27.
    Kempe, M.; Mosbach, K., Receptor binding mimetics: A novel molecularly imprinted polymer receptor, Tetrahedron Lett. 1995, 36, 3563–3566CrossRefGoogle Scholar
  28. 28.
    Hart, B. R.; Shea, K. J., Synthetic peptide receptors: Molecularly imprinted polymers for the recognition of peptides using peptide-metal interactions, J. Am. Chem. Soc. 2001, 123, 2072–2073CrossRefGoogle Scholar
  29. 29.
    Lanza, F.; Hall, A. J.; Sellergren, B.; Bereczki, A.; Horvai, G.; S; Cormack, P. A. G.; Sherrington, D. C., Development of a semiautomated procedure for the synthesis and of molecularly imprinted polymers applied to the search for functional monomers for phenytoin and nifedipine, Anal. Chim. Acta 2001, 435, 91–106CrossRefGoogle Scholar
  30. 30.
    Dirion, B.; Schillinger, E.; Sellergren, B., Development of a high throughput synthesis technique for the optimization of mips for 17b-estradiol, Mat. Res. Soc. 787 (Mat. Res. Soc. Fall Meeting) Boston, 53–59 (2003)Google Scholar
  31. 31.
    Hunt, C. E.; Ansell, R. J., Use of fluorescence shift and fluorescence anisotropy to evaluate the re-binding of template to (s)-propranolol imprinted polymers, Analyst 2006, 131, 678–683CrossRefGoogle Scholar
  32. 32.
    Greene, N.; Lee, J.-D.; Hong, J.-I.; Shimizu, K., Employing molecular imprinted polymers for sensor discrimination, Polymer Preprints (Amer. Chem. Soc., Division of Polym. Chemistry) 2005, 46, 139–140Google Scholar
  33. 33.
    Ye, L.; Mosbach, K., Polymers recognizing biomolecules based on a combination of molecular imprinting and proximity scintillation: A new sensor concept, J. Am. Chem. Soc. 2001, 123, 2901–2902CrossRefGoogle Scholar
  34. 34.
    Manesiotis, P.; Hall, A. J.; Emgenbroich, M.; Quaglia, M.; de Lorenzi, E.; Sellergren, B., An enantioselective imprinted receptor for z-glutamate exhibiting a binding induced color change, Chem. Comm. 2004, 2278–2279Google Scholar
  35. 35.
    Perez-Moral, N.; Mayes, A. G., Direct rapid synthesis of mip beads in spe cartridges, Biosens. Bioelectron. 2006, 21, 1798–1803CrossRefGoogle Scholar
  36. 36.
    Ferrer, I.; Lanza, F.; Tolokan, A.; Horvath, V.; Sellergren, B.; Horvai, G.; Barcelo, D., Selective trace enrichment of chlorotriazine pesticides from waters and sediment samples using terbuthylazine, Anal. Chem. 2000, 72, 3934–3941CrossRefGoogle Scholar
  37. 37.
    Rachkov, A.; McNiven, S.; Cheong, S.-H.; El’Skaya, A.; Yano, K.; Karube, I., Molecularly imprinted polymers selective for Beta-estradiol, Supramol. Chem. 1998, 9, 317–323CrossRefGoogle Scholar
  38. 38.
    Haginaka, J.; Sanbe, H., Uniform-sized molecularly imprinted polymers for.Beta.-estradiol, Chem. Lett. 1998, 1089–1090Google Scholar
  39. 39.
    Idziak, I.; Benrebouh, A., A molecularly imprinted polymer for 17.Alpha.-ethynylestradiol evaluated by immunoassay, Analyst 2000, 125, 1415–1417CrossRefGoogle Scholar
  40. 40.
    Ye, L.; Yu, Y.; Mosbach, K., Towards the development of molecularly imprinted artificial receptors for the screening of estrogenic chemicals, Analyst 2001, 126, 760–765CrossRefGoogle Scholar
  41. 41.
    Special issue on molecular imprints and related approaches for solid-phase extraction and sensors in chemical analysis; Barceló, D., Ed.; 1999; Vol. 18Google Scholar
  42. 42.
    Lanza, F.; Sellergren, B., The application of molecular imprinting technology to solid phase extraction, Chromatographia 2001, 53, 599–611CrossRefGoogle Scholar
  43. 43.
    Sellergren, B., Imprinted dispersion polymers: A new class of easily accessible affinity stationary phases, J. Chromatogr. A 1994, 673, 133–141CrossRefGoogle Scholar
  44. 44.
    Eriksson, L.; Johansson, E.; Kettaneh-Wold, N.; Wikström, C.; Wold, S. Design of experiments. Principles and applications; Umetrics AB: Umeå, 2000Google Scholar
  45. 45.
    Andersson, L. I.; Schweitz, L., Solid-phase extraction on molecularly imprinted polymers, Handbook of Analytical Separations 2003, 4, 45–71CrossRefGoogle Scholar
  46. 46.
    Andersson, L. I., Efficient sample pre-concentration of bupivacaine from human plasma solid-phase extraction on molecularly imprinted polymers, Analyst 2000, 125, 1515–1517CrossRefGoogle Scholar
  47. 47.
    Cobb, Z.; Sellergren, B.; Andersson, Water-compatible molecularly imprinted polymers for efficient direct injection on-lin solid phase extraction of ropivacaine and bupivacaine from human plasma. Analyst 2007, 132, 1262–71CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Börje Sellergren
    • 1
  • Eric Schillinger
    • 1
  • Francesca Lanza
    • 1
  1. 1.INFUUniversität DortmundDortmundGermany

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