Preparation of Molecularly Imprinted Microspheres by Precipitation Polymerization

  • Tibor Renkecz
  • Viola Horvath
Part of the Methods in Molecular Biology book series (MIMB, volume 1575)


Molecularly imprinted polymers (MIPs) gained an expansively growing interest in the past few decades. After an initial, explorative period of preparing MIPs exclusively with bulk polymerization, new polymer synthesis routes have been adapted to overcome the drawbacks of the traditional method. Among these the most appealing is precipitation polymerization that results in nano- and microspheres with narrow size distribution and makes the production of MIPs more straightforward. Here, we describe a precipitation polymerization protocol for a common small molecule template, propranolol that is carried out in the conventional way, in dilute monomer solution. Moreover, a modified precipitation polymerization protocol from concentrated monomer solution is presented for a diclofenac imprinted polymer which makes the synthesis even more versatile and circumvents the disadvantages of the dilute solution conditions.

Key words

Molecularly imprinted polymer Polymer microsphere Precipitation polymerization Monodisperse Modified precipitation polymerization Propranolol Diclofenac 



The authors gratefully acknowledge the financial support of the Hungarian Scientific Fund (Grant K104724).


  1. 1.
    van Herk AM, Monteiro M (2002) Heterogeneous systems. In: Matyjaszewski K, Davis TP (eds) Handbook of radical polymerization. John Wiley and Sons, Inc., HobokenGoogle Scholar
  2. 2.
    Flores A, Cunliff D, Whitcombe MJ, Vulfson EN (2000) Imprinted polymers prepared by aqueous suspension polymerization. J Appl Polym Sci 77(8):1841–1850CrossRefGoogle Scholar
  3. 3.
    Kempe H, Kempe M (2004) Novel method for the synthesis of molecularly imprinted polymer bead libraries. Macromol Rapid Commun 25(1):315–320CrossRefGoogle Scholar
  4. 4.
    Mayes AG, Mosbach K (1996) Molecularly imprinted polymer beads: Suspension polymerization using a liquid perfluorocarbon as the dispersing phase. Anal Chem 68(21):3769–3774CrossRefPubMedGoogle Scholar
  5. 5.
    Perez N, Whitcombe MJ, Vulfson EN (2000) Molecularly imprinted nanoparticles prepared by core-shell emulsion polymerization. J Appl Polym Sci 77(8):1851–1859. doi: 10.1002/1097-4628(20000822)77:81851::aid-app23>;2-j
  6. 6.
    Vaihinger D, Landfester K, Krauter I, Brunner H, Tovar GEM (2002) Molecularly imprinted polymer nanospheres as synthetic affinity receptors obtained by miniemulsion polymerisation. Macromol Chem Phys 203(13):1965–1973. doi: 10.1002/1521-3935(200209)203:13<1965::aid-macp1965>;2-c CrossRefGoogle Scholar
  7. 7.
    Hosoya K, Yoshizako K, Tanaka N, Kimata K, Araki T, Haginaka J (1994) Uniform-size macroporous polymer-based stationary-phase for HPLC prepared through molecular imprinting technique. Chem Lett 8:1437–1438CrossRefGoogle Scholar
  8. 8.
    Sellergren B (1994) Imprinted dispersion polymers—a new class of easily accessible affinity stationary phases. J Chromatogr A 673(1):133–141CrossRefGoogle Scholar
  9. 9.
    Ye L, Cormack PAG, Mosbach K (1999) Molecularly imprinted monodisperse microspheres for competitive radioassay. Anal Commun 36(2):35–38CrossRefGoogle Scholar
  10. 10.
    Ye L, Weiss R, Mosbach K (2000) Synthesis and characterization of molecularly imprinted microspheres. Macromolecules 33(22):8239–8245CrossRefGoogle Scholar
  11. 11.
    Li K, Stover HDH (1993) Synthesis of monodisperse poly(divibylbenzene) microspheres. J Polym Sci Part A: Polym Chem 31(13):3257–3263. doi: 10.1002/pola.1993.080311313 CrossRefGoogle Scholar
  12. 12.
    Horvath V, Lorantfy B, Toth B, Bognar J, Laszlo K, Horvai G (2009) Preparation of terbutylazine imprinted polymer microspheres using viscous polymerization solvents. J Sep Sci 32(19):3347–3358. doi: 10.1002/jssc.200900230 CrossRefPubMedGoogle Scholar
  13. 13.
    Renkecz T, Laszlo K, Horvath V (2012) In situ synthesis of molecularly imprinted nanoparticles in porous support membranes using high-viscosity polymerization solvents. J Mol Recognit 25(6):320–329. doi: 10.1002/jmr.2153 CrossRefPubMedGoogle Scholar
  14. 14.
    Renkecz T, László K, Horvath V (2014) Molecularly imprinted microspheres prepared by precipitation polymerization at high monomer concentrations. Mol Imprintig 2:1–17. doi: 10.2478/molim-2014-0001 CrossRefGoogle Scholar
  15. 15.
    Goh ECC, Stover HDH (2002) Cross-linked poly(methacrylic acid-co-poly(ethylene oxide) methyl ether methacrylate) microspheres and microgels prepared by precipitation polymerization: a morphology study. Macromolecules 35(27):9983–9989. doi: 10.1021/ma0211028 CrossRefGoogle Scholar
  16. 16.
    Benito-Pena E, Navarro-Villoslada F, Carrasco S, Jockusch S, Ottaviani MF, Moreno-Bondi MC (2015) Experimental mixture design as a tool for the synthesis of antimicrobial selective molecularly imprinted monodisperse microbeads. ACS Appl Mater Interfaces 7(20):10966–10976. doi: 10.1021/acsami.5b02238 CrossRefPubMedGoogle Scholar
  17. 17.
    Chen LX, Xu SF, Li JH (2011) Recent advances in molecular imprinting technology: current status, challenges and highlighted applications. Chem Soc Rev 40(5):2922–2942. doi: 10.1039/c0cs00084a CrossRefPubMedGoogle Scholar
  18. 18.
    Shim SE, Yang S, Jin MJ, Chang YH, Choe S (2004) Effect of the polymerization parameters on the morphology and spherical particle size of poly(styrene-co-divinylbenzene) prepared by precipitation polymerization. Colloid Polym Sci 283(1):41–48. doi: 10.1007/s00396-004-1086-3 CrossRefGoogle Scholar
  19. 19.
    Wang JF, Cormack PAG, Sherrington DC, Khoshdel E (2007) Synthesis and characterization of micrometer-sized molecularly imprinted spherical polymer particulates prepared via precipitation polymerization. Pure Appl Chem 79(9):1505–1519. doi: 10.1351/pac200779091505 CrossRefGoogle Scholar
  20. 20.
    Yoshimatsu K, Reimhult K, Krozer A, Mosbach K, Sode K, Ye L (2007) Uniform molecularly imprinted microspheres and nanoparticles prepared by precipitation polymerization: The control of particle size suitable for different analytical applications. Anal Chim Acta 584(1):112–121CrossRefPubMedGoogle Scholar
  21. 21.
    Jiang JS, Zhang Y, Guo XZ, Zhang HQ (2011) Narrow or monodisperse, highly cross-linked, and “living” polymer microspheres by atom transfer radical precipitation polymerization. Macromolecules 44(15):5893–5904. doi: 10.1021/ma201038e CrossRefGoogle Scholar
  22. 22.
    Li WH, Stover HDH (1998) Porous monodisperse poly(divinylbenzene) microspheres by precipitation polymerization. J Polym Sci Part A Polym Chem 36(10):1543–1551. doi: 10.1002/(sici)1099-0518(19980730)36:10<1543::aid-pola7>;2-r CrossRefGoogle Scholar
  23. 23.
    Kempe H, Kempe M (2010) Influence of salt ions on binding to molecularly imprinted polymers. Anal Bioanal Chem 396(4):1599–1606. doi: 10.1007/s00216-009-3329-0 CrossRefPubMedGoogle Scholar
  24. 24.
    Zhang YG, Song D, Lanni LM, Shimizu KD (2010) Importance of functional monomer dimerization in the molecular imprinting process. Macromolecules 43(15):6284–6294. doi: 10.1021/ma101013c CrossRefGoogle Scholar
  25. 25.
    Moreno-Bondi MC, Urraca JL, Carrasco S, Navarro-Villoslada F (2013) Preparation of molecularly imprinted polymers. In: Alvarez-Lorenzo C, Concheiro A (eds) Handbook of molecularly imprinted polymers. Smithers Rapra, Shawbury, Shrewsbury, pp 23–86Google Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Department of Inorganic and Analytical ChemistryBudapest University of Technology and EconomicsBudapestHungary

Personalised recommendations