Rational design of biomimetic molecularly imprinted materials: theoretical and computational strategies for guiding nanoscale structured polymer development

  • Ian A. NichollsEmail author
  • Håkan S. Andersson
  • Kerstin Golker
  • Henning Henschel
  • Björn C. G. Karlsson
  • Gustaf D. Olsson
  • Annika M. Rosengren
  • Siamak Shoravi
  • Subramanian Suriyanarayanan
  • Jesper G. Wiklander
  • Susanne Wikman


In principle, molecularly imprinted polymer science and technology provides a means for ready access to nano-structured polymeric materials of predetermined selectivity. The versatility of the technique has brought it to the attention of many working with the development of nanomaterials with biological or biomimetic properties for use as therapeutics or in medical devices. Nonetheless, the further evolution of the field necessitates the development of robust predictive tools capable of handling the complexity of molecular imprinting systems. The rapid growth in computer power and software over the past decade has opened new possibilities for simulating aspects of the complex molecular imprinting process. We present here a survey of the current status of the use of in silico-based approaches to aspects of molecular imprinting. Finally, we highlight areas where ongoing and future efforts should yield information critical to our understanding of the underlying mechanisms sufficient to permit the rational design of molecularly imprinted polymers.


Ab initio Biomaterials Biomimetic Chemometrics Molecularly imprinted polymer Molecular dynamics Semi-empirical 



The financial support provided by the Swedish Research Council (VR), the Crafoord Foundation, the Swedish Knowledge Foundation (KKS), and the Linnaeus University is most gratefully acknowledged.


  1. 1.
    Galaev IY, Mattiasson B (1999) ‘Smart’ polymers and what they could do in biotechnology and medicine. Trends Biotechnol 17:335–340Google Scholar
  2. 2.
    Alexander C, Andersson HS, Andersson LI, Ansell RJ, Kirsch N, Nicholls IA, O’Mahony J, Whitcombe MJ (2006) Molecular imprinting science and technology: a survey of the literature for the years up to and including 2003. J Mol Recognit 19:106–180Google Scholar
  3. 3.
    Wulff G (2002) Enzyme-like catalysis by molecularly imprinted polymers. Chem Rev 102:1–27Google Scholar
  4. 4.
    Haupt K, Mosbach K (2000) Molecularly imprinted polymers and their use in biomimetic sensors. Chem Rev 100:2495–2504Google Scholar
  5. 5.
    Svenson J, Nicholls IA (2001) On the thermal and chemical stability of molecularly imprinted polymers. Anal Chim Acta 435:19–24Google Scholar
  6. 6.
    Vlatakis G, Andersson LI, Muller R, Mosbach K (1993) Drug assay using antibody mimics made by molecular imprinting. Nature 361:645–647Google Scholar
  7. 7.
    Andersson LI, Müller R, Vlatakis G, Mosbach K (1995) Mimics of the binding sites of opioid receptors obtained by molecular imprinting of enkephalin and morphine. Proc Natl Acad Sci U S A 92:4788–4792Google Scholar
  8. 8.
    Berglund J, Nicholls IA, Lindbladh C, Mosbach K (1996) Recognition in molecularly imprinted polymer alpha(2)-adrenoreceptor mimics. Bioorg Med Chem Lett 6:2237–2242Google Scholar
  9. 9.
    Berglund J, Lindbladh C, Nicholls IA, Mosbach K (1998) Selection of phage display combinatorial library peptides with affinity for a yohimbine imprinted methacrylate polymer. Anal Commun 35:3–7Google Scholar
  10. 10.
    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 126:7452–7453Google Scholar
  11. 11.
    Liu JQ, Wulff G (2004) Molecularly imprinted polymers with strong carboxypeptidase A-like activity: combination of an amidinium function with a zinc-ion binding site in transition-state imprinted cavities. Angew Chem Int Ed 43:1287–1290Google Scholar
  12. 12.
    Svenson J, Zheng N, Nicholls IA (2004) A molecularly imprinted polymer-based synthetic transaminase. J Am Chem Soc 126:8554–8560Google Scholar
  13. 13.
    Thomas NR (1994) Hapten design for the generation of catalytic antibodies. Appl Biochem Biotechnol 47:345–372Google Scholar
  14. 14.
    Norell MC, Andersson HS, Nicholls IA (1998) Theophylline molecularly imprinted polymer dissociation kinetics: a novel sustained release drug dosage mechanism. J Mol Recognit 11:98–102Google Scholar
  15. 15.
    Sellergren B, Allender CJ (2005) Molecularly imprinted polymers: a bridge to advanced drug delivery. Adv Drug Deliv Rev 57:1733–1741Google Scholar
  16. 16.
    Ciardelli G, Montevecchi FM, Giusti P, Silvestri D, Morelli I, Cristallini C, Vozzi G (2006) Molecular imprinted nanostructures in biomedical applications. Proc ASME Des Eng Tech Conf 2006:561–567Google Scholar
  17. 17.
    Silvestri D, Cristallini C, Borrelli C, Barbani N, Giusti P, Ciardelli G (2007) Composite membranes modified with recognition-able nanobeads as potential adsorbers for purification of biological fluids. J Appl Biomater Biomech 5:166–175Google Scholar
  18. 18.
    White CJ, Byrne ME (2010) Molecularly imprinted therapeutic contact lenses. Expert Opin Drug Deliv 7:765–780Google Scholar
  19. 19.
    Ali M, Byrne ME (2009) Controlled release of high molecular weight hyaluronic acid from molecularly imprinted hydrogel contact lenses. Pharm Res 26:714–726Google Scholar
  20. 20.
    Hiratani H, Mizutani Y, Alvarez-Lorenzo C (2005) Controlling drug release from imprinted hydrogels by modifying the characteristics of the imprinted cavities. Macromol Biosci 5:728–733Google Scholar
  21. 21.
    Hiratani H, Fujiwara A, Tamiya Y, Mizutani Y, Alvarez-Lorenzo C (2005) Ocular release of timolol from molecularly imprinted soft contact lenses. Biomaterials 26:1293–1298Google Scholar
  22. 22.
    Hiratani H, Alvarez-Lorenzo C (2004) The nature of backbone monomers determines the performance of imprinted soft contact lenses as timolol drug delivery systems. Biomaterials 25:1105–1113Google Scholar
  23. 23.
    Hiratani H, Alvarez-Lorenzo C (2002) Timolol uptake and release by imprinted soft contact lenses made of N,N-diethylacrylamide and methacrylic acid. J Control Release 83:223–230Google Scholar
  24. 24.
    Nicholls IA, Nilsson-Ekdahl K (2009) Molecular imprints. Swedish patent application 0901541–3Google Scholar
  25. 25.
    Hoshino Y, Koide H, Urakami T, Kanazawa H, Kodama T, Oku N, Shea KJ (2010) Recognition, neutralization, and clearance of target peptides in the bloodstream of living mice by molecularly imprinted polymer nanoparticles: a plastic antibody. J Am Chem Soc 132:6644–6645Google Scholar
  26. 26.
    Batra D, Shea KJ (2003) Combinatorial methods in molecular imprinting. Curr Opin Chem Biol 7:434–442Google Scholar
  27. 27.
    Sellergren B (ed) (2001) Molecularly imprinted polymers: man-made mimics of antibodies and their applications in analytical chemistry. Elsevier, AmsterdamGoogle Scholar
  28. 28.
    Komiyama M, Takeuchi T, Mukawa T, Asanuma H (2002) Molecular imprinting: from fundamentals to applications. Wiley-VCH, WeinheimGoogle Scholar
  29. 29.
    Yan M, Ramström O (eds) (2005) Molecularly imprinted materials: science and technology. Marcel Dekker, New YorkGoogle Scholar
  30. 30.
    Piletsky SA, Turner APF (eds) (2006) Molecular imprinting of polymers. Landes Bioscience, GeorgetownGoogle Scholar
  31. 31.
    Nicholls IA (1995) Thermodynamic considerations for the design of and ligand recognition by molecularly imprinted polymers. Chem Lett 24:1035–1036Google Scholar
  32. 32.
    Nicholls IA, Adbo K, Andersson HS, Andersson PO, Ankarloo J, Hedin-Dahlström J, Jokela P, Karlsson JG, Olofsson L, Rosengren J, Shoravi S, Svenson J, Wikman S (2001) Can we rationally design molecularly imprinted polymers? Anal Chim Acta 435:9–18Google Scholar
  33. 33.
    Pande VS, Grosberg AY, Tanaka T (1997) How to create polymers with protein-like capabilities: a theoretical suggestion. Phys Dir 107:316–321Google Scholar
  34. 34.
    Nicholls IA (1998) Towards the rational design of molecularly imprinted polymers. J Mol Recognit 11:79–82Google Scholar
  35. 35.
    Piletsky SA, Panasyuk TL, Piletskaya EV, Nicholls IA, Ulbricht M (1999) Receptor and transport properties of imprinted polymer membranes - a review. J Membr Sci 157:263–278Google Scholar
  36. 36.
    Piletsky SA, Piletska EV, Karim K, Freebairn KW, Legge CH, Turner APF (2002) Polymer cookery: influence of polymerization conditions on the performance of molecularly imprinted polymers. Macromolecules 35:7499–7504Google Scholar
  37. 37.
    Piletsky SA, Guerreiro A, Piletska EV, Chianella I, Karim K, Turner APF (2004) Polymer cookery. 2. Influence of polymerization pressure and polymer swelling on the performance of molecularly imprinted polymers. Macromolecules 37:5018–5022Google Scholar
  38. 38.
    Piletsky SA, Mijangos I, Guerreiro A, Piletska EV, Chianella I, Karim K, Turner APF (2005) Polymer cookery: influence of polymerization time and different initiation conditions on performance of molecularly imprinted polymers. Macromolecules 38:1410–1414Google Scholar
  39. 39.
    Leach AR (2001) Molecular dynamics simulation methods. In: Molecular modelling: principles and applications, 2nd edn. Prentice Hall, HarlowGoogle Scholar
  40. 40.
    Alder BJ, Wainwright TE (1957) Phase transition for a hard sphere system. J Chem Phys 27:1208–1209Google Scholar
  41. 41.
    Wang J, Cieplak P, Kollman PA (2000) How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J Comput Chem 21:1049–1074Google Scholar
  42. 42.
    Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25:1157–1174Google Scholar
  43. 43.
    Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) CHARMM: a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 4:187–217Google Scholar
  44. 44.
    Jorgensen WL, Maxwell DS, Tirado-Rives J (1996) Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc 118:11225–11236Google Scholar
  45. 45.
    Berendsen HJC, van der Spoel D, van Drunen R (1995) GROMACS: a message-passing parallel molecular dynamics implementation. Comput Phys Commun 91:43–56Google Scholar
  46. 46.
    Scott WRP, Hunenberger PH, Tironi IG, Mark AE, Billeter SR, Fennen J, Torda AE, Huber T, Kruger P, van Gunsteren WF (1999) The GROMOS biomolecular simulation program package. J Phys Chem A 103:3596–3607Google Scholar
  47. 47.
    Duan Y, Kollman PA (1998) Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution. Science 282:740Google Scholar
  48. 48.
    Pervushin K, Riek R, Wider G, Wüthrich K (1997) Attenuated T2 relaxation by mutual cancellation of dipole–dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution. Proc Natl Acad Sci U S A 94:12366–12371Google Scholar
  49. 49.
    Cheatham TEI, Kollman PA (1996) Observation of the A-DNA to B-DNA transition during unrestrained molecular dynamics in aqueous solution. J Mol Biol 259:434–444Google Scholar
  50. 50.
    `Cheatham TEI, Miller JL, Fox T, Darden TA, Kollman PA (1995) Molecular dynamics simulations on solvated biomolecular systems: the particle mesh Ewald method leads to stable trajectories of DNA, RNA, and proteins. J Am Chem Soc 117:4193–4194Google Scholar
  51. 51.
    Berger O, Edholm O, Jahnig F (1997) Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J 72:2002–2013Google Scholar
  52. 52.
    van der Ploeg P, Berendsen HJC (1982) Molecular dynamics simulation of a bilayer membrane. J Chem Phys 76:3271–3276Google Scholar
  53. 53.
    de Groot BL, Grubmuller H (2001) Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF. Science 294:2353–2357Google Scholar
  54. 54.
    van Buuren AR, Marrink SJ, Berendsen HJC (1993) A molecular dynamics study of the decane/water interface. J Phys Chem 97:9206–9212Google Scholar
  55. 55.
    Hsu QC, Wu CD, Fang TH (2005) Studies on nanoimprint process parameters of copper by molecular dynamics analysis. Comput Mater Sci 34:314–322Google Scholar
  56. 56.
    Garrison BJ, Delcorte A, Krantzman KD (2000) Molecule liftoff from surfaces. Acc Chem Res 33:69–77Google Scholar
  57. 57.
    Masukawa KM, Kollman PA, Kuntz ID (2003) Investigation of neuraminidase-substrate recognition using molecular dynamics and free energy calculations. J Med Chem 46:5628–5637Google Scholar
  58. 58.
    Yang H, Elcock AH (2003) Association lifetimes of hydrophobic amino acid pairs measured directly from molecular dynamics simulations. J Am Chem Soc 125:13968–13969Google Scholar
  59. 59.
    Li X, Eriksson L (2005) Molecular dynamics study of lignin constituents in water. Holzforschung 59:253–262Google Scholar
  60. 60.
    Piletsky SA, Karim K, Piletska EV, Day CJ, Freebairn KW, Legge CH (2001) Recognition of ephedrine enantiomers by molecularly imprinted polymers designed using a computational approach. Analyst 126:1826–1830Google Scholar
  61. 61.
    Piletska EV, Turner NW, Turner APF, Piletsky SA (2005) Controlled release of the herbicide simazine from computationally designed molecularly imprinted polymers. J Control Release 108:132–139Google Scholar
  62. 62.
    Piletska EV, Romero-Guerra M, Guerreiro AR, Karim K, Turner APF, Piletsky SA (2005) Adaptation of the molecular imprinted polymers towards polar environment. Anal Chim Acta 542:47–51Google Scholar
  63. 63.
    Piletska EV, Romero-Guerra M, Chianella I, Karim K, Turner AR, Piletsky SA (2005) Towards the development of multisensor for drugs of abuse based on molecular imprinted polymers. Anal Chim Acta 542:111–117Google Scholar
  64. 64.
    Subrahmanyam S, Piletsky SA, Piletska EV, Chen B, Karim K, Turner APF (2001) ‘Bite-and-Switch’ approach using computationally designed molecularly imprinted polymers for sensing of creatinine. Biosens Bioelectron 16:631–637Google Scholar
  65. 65.
    Piletska EV, Piletsky SA, Karim K, Terpetschnig E, Turner APF (2004) Biotin-specific synthetic receptors prepared using molecular imprinting. Anal Chim Acta 504:179–183Google Scholar
  66. 66.
    Chianella I, Lotierzo M, Piletsky SA, Tothill IE, Chen B, Karim K, Turner APF (2002) Rational design of a polymer specific for microcystin-LR using a computational approach. Anal Chem 74:1288–1293Google Scholar
  67. 67.
    Chianella I, Piletsky SA, Tothill IE, Chen B, Turner APF (2003) MIP-based solid phase extraction cartridges combined with MIP-based sensors for the detection of microcystin-LR. Biosens Bioelectron 18:119–127Google Scholar
  68. 68.
    Wei S, Jakusch M, Mizaikoff B (2007) Investigating the mechanisms of 17β-estradiol imprinting by computational prediction and spectroscopic analysis. Anal Bioanal Chem 389:423–431Google Scholar
  69. 69.
    Pavel D, Lagowski J (2005) Computationally designed monomers and polymers for molecular imprinting of theophylline and its derivatives. Part I. Polymer 46:7528–7542Google Scholar
  70. 70.
    Pavel D, Lagowski J (2005) Computationally designed monomers and polymers for molecular imprinting of theophylline—part II. Polymer 46:7543–7556Google Scholar
  71. 71.
    Pavel D, Lagowski J, Lepage CJ (2006) Computationally designed monomers for molecular imprinting of chemical warfare agents—part V. Polymer 47:8389–8399Google Scholar
  72. 72.
    Monti S, Cappelli C, Bronco S, Giusti P, Ciardelli G (2006) Towards the design of highly selective recognition sites into molecular imprinting polymers: a computational approach. Biosens Bioelectron 22:153–163Google Scholar
  73. 73.
    Lv Y, Lin Z, Tan T, Feng W, Qin P, Li C (2008) Application of molecular dynamics modeling for the prediction of selective adsorption properties of dimethoate imprinting polymer. Sens Actuators B 133:15–23Google Scholar
  74. 74.
    Yoshida M, Hatate Y, Uezu K, Goto M, Furusaki S (2000) Chiral-recognition polymer prepared by surface molecular imprinting technique. Colloids Surf A 169:259–269Google Scholar
  75. 75.
    Toorisaka E, Uezu K, Goto M, Furusaki S (2003) A molecularly imprinted polymer that shows enzymatic activity. Biochem Eng J 14:85–91Google Scholar
  76. 76.
    Dong C, Li X, Guo Z, Qi J (2009) Development of a model for the rational design of molecular imprinted polymer: computational approach for combined molecular dynamics/quantum mechanics calculations. Anal Chim Acta 647:117–124Google Scholar
  77. 77.
    Liu R, Li X, Li Y, Jin P, Qin W, Qi J (2009) Effective removal of rhodamine B from contaminated water using non-covalent imprinted microspheres designed by computational approach. Biosens Bioelectron 25:629–634Google Scholar
  78. 78.
    Li Y, Li X, Li Y, Dong C, Jin P, Qi J (2009) Selective recognition of veterinary drugs residues by artificial antibodies designed using a computational approach. Biomaterials 30:3205–3211Google Scholar
  79. 79.
    Svenson J, Karlsson JG, Nicholls IA (2004) 1H Nuclear magnetic resonance study of the molecular imprinting of (−)-nicotine: template self-association, a molecular basis for cooperative ligand binding. J Chromatogr A 1024:39–44Google Scholar
  80. 80.
    Andersson HS, Karlsson JG, Piletsky SA, Koch-Schmidt A, Mosbach K, Nicholls IA (1999) Study of the nature of recognition in molecularly imprinted polymers, II [1] Influence of monomer-template ratio and sample load on retention and selectivity. J Chromatogr A 848:39–49Google Scholar
  81. 81.
    Katz A, Davis ME (1999) Investigations into the mechanisms of molecular recognition with imprinted polymers. Macromolecules 32:4113–4121Google Scholar
  82. 82.
    Olsson GD, Karlsson BCG, Shoravi S, Wiklander JG, Nicholls IA (2010) Mechanisms underlying molecularly imprinted polymer molecular memory and the role of cross-linker: resolving conjecture on the nature of template recognition in phenylalanine anilide imprinted polymers. J Mol Recognit (submitted)Google Scholar
  83. 83.
    Karlsson BCG, Rosengren AM, Andersson PO, Nicholls IA (2007) The spectrophysics of warfarin: implications for protein binding. J Phys Chem B 111:10520–10528Google Scholar
  84. 84.
    Karlsson BCG, Rosengren AM, Andersson PO, Nicholls IA (2009) Molecular insights on the two fluorescence lifetimes displayed by warfarin from fluorescence anisotropy and molecular dynamics studies. J Phys Chem B 113:7945–7949Google Scholar
  85. 85.
    Henschel H, Karlsson BCG, Rosengren AM, Nicholls IA (2010) The mechanistic basis for warfarin’s structural diversity and implications for its bioavailability. J Mol Struct Theochem 958:7–9Google Scholar
  86. 86.
    Nicholls IA, Karlsson BCG, Rosengren AM, Henschel H (2010) Warfarin: an environment-dependent switchable molecular probe. J Mol Recognit 23:604–608Google Scholar
  87. 87.
    Karlsson BCG, Rosengren AM, Näslund I, Andersson PO, Nicholls IA (2010) Synthetic human serum albumin Sudlow I binding site mimics. J Med Chem 53:7932–7937Google Scholar
  88. 88.
    Rosengren AM, Karlsson BCG, Näslund I, Andersson PO, Nicholls IA (2011) In situ detection of warfarin using time-correlated single-photon counting. Biochem Biophys Res Commun 407:60–62Google Scholar
  89. 89.
    Ansell RJ, Kuah KL (2005) Imprinted polymers for chiral resolution of (±)-ephedrine: understanding the pre-polymerisation equilibrium and the action of different mobile phase modifiers. Analyst 130:179–187Google Scholar
  90. 90.
    Ansell RJ, Wang D, Kuah JKL (2008) Imprinted polymers for chiral resolution of (±)-ephedrine. Part 2: probing pre-polymerisation equilibria in different solvents by NMR. Analyst 133:1673–1683Google Scholar
  91. 91.
    Ansell RJ, Wang DY (2009) Imprinted polymers for chiral resolution of (±)-ephedrine. Part 3: NMR predictions and HPLC results with alternative functional monomers. Analyst 134:564–576Google Scholar
  92. 92.
    Molinelli A, O’Mahony J, Nolan K, Smyth MR, Jakusch M, Mizaikoff B (2005) Analyzing the mechanisms of selectivity in biomimetic self-assemblies via IR and NMR spectroscopy of prepolymerization solutions and molecular dynamics simulations. Anal Chem 77:5196–5204Google Scholar
  93. 93.
    O’Mahony J, Karlsson BCG, Mizaikoff B, Nicholls IA (2007) Correlated theoretical, spectroscopic and x-ray crystallographic studies of a non-covalent molecularly imprinted polymerisation system. Analyst 132:1161–1168Google Scholar
  94. 94.
    O’Mahony J, Wei S, Molinelli A, Mizaikoff B (2006) Imprinted polymeric materials. Insight into the nature of prepolymerization complexes of quercetin imprinted polymers. Anal Chem 78:6187–6190Google Scholar
  95. 95.
    Karlsson BCG, O’Mahony J, Karlsson JG, Bengtsson H, Eriksson LA, Nicholls IA (2009) Structure and dynamics of monomer−template complexation: an explanation for molecularly imprinted polymer recognition site heterogeneity. J Am Chem Soc 131:13297–13304Google Scholar
  96. 96.
    Karlsson JG, Karlsson BCG, Andersson LI, Nicholls IA (2004) The roles of template complexation and ligand binding conditions on recognition in bupivacaine molecularly imprinted polymers. Analyst 129:456–462Google Scholar
  97. 97.
    Srebnik S, Lev O, Avnir D (2001) Pore size distribution induced by microphase separation: effect of the leaving group during polycondensation. Chem Mater 13:811–816Google Scholar
  98. 98.
    Srebnik S, Lev O (2002) Toward establishing criteria for polymer imprinting using mean-field theory. J Chem Phys 116:10967–10972Google Scholar
  99. 99.
    Srebnik S (2004) Theoretical investigation of the imprinting efficiency of molecularly imprinted polymers. Chem Mater 16:883–888Google Scholar
  100. 100.
    Yungerman I, Srebnik S (2006) Factors contributing to binding-site imperfections in imprinted polymers. Chem Mater 18:657–663Google Scholar
  101. 101.
    Zhao Z, Wang Q, Zhang L, Wu T (2008) Structured water and water−polymer interactions in hydrogels of molecularly imprinted polymers. J Phys Chem B 112:7515–7521Google Scholar
  102. 102.
    Fu Q, Sanbe H, Kagawa C, Kunimoto KK, Haginaka J (2003) Uniformly sized molecularly imprinted polymer for (S)-nilvadipine. Comparison of chiral recognition ability with HPLC chiral stationary phases based on a protein. Anal Chem 75:191–198Google Scholar
  103. 103.
    Schwarz L, Holdsworth CI, McCluskey A, Bowyer MC (2004) Synthesis and evaluation of a molecularly imprinted polymer selective to 2,4,6-trichlorophenol. Aust J Chem 57:759–764Google Scholar
  104. 104.
    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 59:939–944Google Scholar
  105. 105.
    Pietrzyk A, Kutner W, Chitta R, Zandler ME, D’Souza F, Sannicolo F, Mussini PR (2009) Melamine acoustic chemosensor based on molecularly imprinted polymer film. Anal Chem 81:10061–10070Google Scholar
  106. 106.
    Demircelik AH, Andac M, Andac CA, Say R, Denizli A (2009) Molecular recognition-based detoxification of aluminum in human plasma. J Biomater Sci Polym Ed 20:1235–1258Google Scholar
  107. 107.
    Riahi S, Edris-Tabrizi F, Javanbakht M, Ganjali MR, Norouzi P (2009) A computational approach to studying monomer selectivity towards the template in an imprinted polymer. J Mol Model 15:829–836Google Scholar
  108. 108.
    Holdsworth CI, Bowyer MC, Lennard C, McCluskey A (2005) Formulation of cocaine-imprinted polymers utilizing molecular modelling and NMR analysis. Aust J Chem 58:315–320Google Scholar
  109. 109.
    Lulinski P, Maciejewska D, Bamburowicz-Klimkowska M, Szutowski M (2007) Dopamine-imprinted polymers: template-monomer interactions, analysis of template removal and application to solid phase extraction. Molecules 12:2434–2449Google Scholar
  110. 110.
    Baggiani C, Anfossi L, Baravalle P, Giovannoli C, Tozzi C (2005) Selectivity features of molecularly imprinted polymers recognising the carbamate group. Anal Chim Acta 531:199–207Google Scholar
  111. 111.
    Dong WG, Yan M, Zhang ML, Liu Z, Li YM (2005) A computational and experimental investigation of the interaction between the template molecule and the functional monomer used in the molecularly imprinted polymer. Anal Chim Acta 542:186–192Google Scholar
  112. 112.
    Gholivand MB, Khodadadian M, Ahmadi F (2010) Computer aided-molecular design and synthesis of a high selective molecularly imprinted polymer for solid-phase extraction of furosemide from human plasma. Anal Chim Acta 658:225–232Google Scholar
  113. 113.
    Alizadeh T (2008) Development of a molecularly imprinted polymer for pyridoxine using an ion-pair as template. Anal Chim Acta 623:101–108Google Scholar
  114. 114.
    Yao JH, Li X, Qin W (2008) Computational design and synthesis of molecular imprinted polymers with high selectivity for removal of aniline from contaminated water. Anal Chim Acta 610:282–288Google Scholar
  115. 115.
    Li Y, Li X, Dong CK, Li YQ, Jin PF, Qi JY (2009) Selective recognition and removal of chlorophenols from aqueous solution using molecularly imprinted polymer prepared by reversible addition-fragmentation chain transfer polymerization. Biosens Bioelectron 25:306–312Google Scholar
  116. 116.
    Kowalska A, Stobiecka A, Wysocki S (2009) A computational investigation of the interactions between harmane and the functional monomers commonly used in molecular imprinting. J Mol Struct Theochem 901:88–95Google Scholar
  117. 117.
    Del Sole R, Lazzoi MR, Arnone M, Della Sala F, Cannoletta D, Vasapollo G (2009) Experimental and computational studies on non-covalent imprinted microspheres as recognition system for nicotinamide molecules. Molecules 14:2632–2649Google Scholar
  118. 118.
    Azenha M, Kathirvel P, Nogueira P, Fernando-Silva A (2008) The requisite level of theory for the computational design of molecularly imprinted silica xerogels. Biosens Bioelectron 23:1843–1849Google Scholar
  119. 119.
    Ogawa T, Hoshina K, Haginaka J, Honda C, Moto TT, Uchida T (2005) Screening of bitterness-suppressing agents for quinine: the use of molecularly imprinted polymers. J Pharm Sci 94:353–362Google Scholar
  120. 120.
    Lai EPC, Feng SY (2003) Molecularly imprinted solid phase extraction for rapid screening of metformin. Microchem J 75:159–168Google Scholar
  121. 121.
    Wu LQ, Sun BW, Li YZ, Chang WB (2003) Study properties of molecular imprinting polymer using a computational approach. Analyst 128:944–949Google Scholar
  122. 122.
    Dineiro Y, Menendez MI, Blanco-Lopez MC, Lobo-Castanon MJ, Miranda-Ordieres AJ, Tunon-Blanco P (2005) Computational approach to the rational design of molecularly imprinted polymers for voltammetric sensing of homovanillic acid. Anal Chem 77:6741–6746Google Scholar
  123. 123.
    Dineiro Y, Menendez MI, Blanco-Lopez MC, Lobo-Castanon MJ, Miranda-Ordieres AJ, Tunon-Blanco P (2006) Computational predictions and experimental affinity distributions for a homovanillic acid molecularly imprinted polymer. Biosens Bioelectron 22:364–371Google Scholar
  124. 124.
    Rathbone DL, Ali A, Antonaki P, Cheek S (2005) Towards a polymeric binding mimic for cytochrome CYP2D6. Biosens Bioelectron 20:2353–2363Google Scholar
  125. 125.
    Sagawa T, Togo K, Miyahara C, Ihara H, Ohkubo K (2004) Rate-enhancement of hydrolysis of long-chain amino acid ester by cross-linked polymers imprinted with a transition-state analogue: evaluation of imprinting effect in kinetic analysis. Anal Chim Acta 504:37–41Google Scholar
  126. 126.
    Voshell SM, Gagné MR (2005) Rigidified dendritic structures for imprinting chiral information. Organometallics 24:6338–6350Google Scholar
  127. 127.
    Miertuš S, Scrocco E, Tomasi J (1981) Electrostatic interaction of a solute with a continuum. A direct utilizaion of AB initio molecular potentials for the prevision of solvent effects. Chem Phys 55:117–129Google Scholar
  128. 128.
    Wu LQ, Zhu KC, Zhao WP, Li YZ (2005) Theoretical and experimental study of nicotinamide molecularly imprinted polymers with different porogens. Anal Chim Acta 549:39–44Google Scholar
  129. 129.
    Liu Y, Wang F, Tan TW, Lei M (2010) Rational design and study on recognition property of paracetamol-imprinted polymer. Appl Biochem Biotechnol 160:328–342Google Scholar
  130. 130.
    Dong WG, Yan M, Liu Z, Wu GS, Li YM (2007) Effects of solvents on the adsorption selectivity of molecularly imprinted polymers: molecular simulation and experimental validation. Sep Purif Technol 53:183–188Google Scholar
  131. 131.
    Wang JC, Guo RB, Chen JP, Zhang Q, Liang XM (2005) Phenylurea herbicides-selective polymer prepared by molecular imprinting using N-(4-isopropylphenyl)-N′-butyleneurea as dummy template. Anal Chim Acta 540:307–315Google Scholar
  132. 132.
    Jacob R, Tate M, Banti Y, Rix C, Mainwaring DE (2008) Synthesis, characterization, and ab initio theoretical study of a molecularly imprinted polymer selective for biosensor materials. J Phys Chem A 112:322–331Google Scholar
  133. 133.
    Wu LQ, Li YZ (2003) Picolinamide-Cu(Ac)(2)-imprinted polymer with high potential for recognition of picolinamide-copper acetate complex. Anal Chim Acta 482:175–181Google Scholar
  134. 134.
    Wu LQ, Li YZ (2004) Metal ion-mediated molecular-imprinting polymer for indirect recognition of formate, acetate and propionate. Anal Chim Acta 517:145–151Google Scholar
  135. 135.
    Christoforidis KC, Louloudi M, Rutherford AW, Deligiannakis Y (2008) Semiquinone in molecularly imprinted hybrid amino acid-SiO2 biomimetic materials. An experimental and theoretical study. J Phys Chem C 112:12841–12852Google Scholar
  136. 136.
    Che AF, Wan LS, Ling J, Liu ZM, Xu ZK (2009) Recognition mechanism of theophylline-imprinted polymers: two-dimensional infrared analysis and density functional theory study. J Phys Chem B 113:7053–7058Google Scholar
  137. 137.
    Shiigi H, Kijima D, Ikenaga Y, Hori K, Fukazawa S, Nagaoka T (2005) Molecular recognition for bile acids using a molecularly imprinted overoxidized polypyrrole film. J Electrochem Soc 152:H129–H134Google Scholar
  138. 138.
    Mukawa T, Goto T, Nariai H, Aoki Y, Imamura A, Takeuchi T (2003) Novel strategy for molecular imprinting of phenolic compounds utilizing disulfide templates. J Pharm Biomed Anal 30:1943–1947Google Scholar
  139. 139.
    Meng ZH, Yamazaki T, Sode K (2004) A molecularly imprinted catalyst designed by a computational approach in catalysing a transesterification process. Biosens Bioelectron 20:1068–1075Google Scholar
  140. 140.
    Wu LQ, Li YZ (2004) Study on the recognition of templates and their analogues on molecularly imprinted polymer using computational and conformational analysis approaches. J Mol Recognit 17:567–574Google Scholar
  141. 141.
    Tada M, Sasaki T, Iwasawa Y (2004) Design of a novel molecular-imprinted Rh-amine complex on SiO2 and its shape-selective catalysis for alpha-methylstyrene hydrogenation. J Phys Chem B 108:2918–2930Google Scholar
  142. 142.
    Esbensen KH (ed) (2002) Multivariate data analysis in practice, 5th edn. Camo Process AS, OsloGoogle Scholar
  143. 143.
    Carlsson R (1992) Design and optimization in organic synthesis. Elsevier, AmsterdamGoogle Scholar
  144. 144.
    Eriksson L, Johansson E, Kettaneh-Wold N, Wold S (2001) Multi- and megavariate data analysis. Principles and application. Umetrics Academy, UmeåGoogle Scholar
  145. 145.
    Navarro-Villoslada F, Vicente BS, Moreno-Bondi MC (2004) Application of multivariate analysis to the screening of molecularly imprinted polymers for bisphenol A. Anal Chim Acta 504:149–162Google Scholar
  146. 146.
    Navarro-Villoslada F, Takeuchi T (2005) Multivariate analysis and experimental design in the screening of combinatorial libraries of molecular imprinted polymers. Bull Chem Soc Jpn 78:1354–1361Google Scholar
  147. 147.
    Davies MP, De Biasi V, Perrett D (2004) Approaches to the rational design of molecularly imprinted polymers. Anal Chim Acta 504:7–14Google Scholar
  148. 148.
    Kempe H, Kempe M (2004) Novel method for the synthesis of molecularly imprinted polymer bead libraries. Macromol Rapid Commun 25:315–320Google Scholar
  149. 149.
    Ceolin G, Navarro-Villoslada F, Moreno-Bondi MC, Horvai G, Horvath V (2009) Accelerated development procedure for molecularly imprinted polymers using membrane filterplates. J Comb Chem 11:645–652Google Scholar
  150. 150.
    Rossi C, Haupt K (2007) Application of the Doehlert experimental design to molecularly imprinted polymers: surface response optimization of specific template recognition as a function of the type and degree of cross-linking. Anal Bioanal Chem 389:455–460Google Scholar
  151. 151.
    Mijangos I, Navarro-Villoslada F, Guerreiro AR, Piletska EV, Chianella I, Karim K, Turner APF, Piletsky SA (2006) Influence of initiator and different polymerisation conditions on performance of molecularly imprinted polymers. Biosens Bioelectron 22:381–387Google Scholar
  152. 152.
    Koohpaei AR, Shahtaheri SJ, Ganjali MR, Forushani AR, Golbabaei F (2008) Application of multivariate analysis to the screening of molecularly imprinted polymers (MIPs) for ametryn. Talanta 75:978–986Google Scholar
  153. 153.
    Tarley CRT, Segatelli MG, Kubota LT (2006) Amperometric determination of chloroguaiacol at submicromolar levels after on-line preconcentration with molecularly imprinted polymers. Talanta 69:259–266Google Scholar
  154. 154.
    Santos WDJR, Lima PR, Tarley CRT, Kubota LT (2007) A catalytically active molecularly imprinted polymer that mimics peroxidase based on hemin: application to the determination of p-aminophenol. Anal Bioanal Chem 389:1919–1929Google Scholar
  155. 155.
    Koohpaei AR, Shahtaheri SJ, Ganjali MR, Forushani AR, Golbabaei F (2008) Molecular imprinted solid phase extraction for determination of atrazine in environmental samples. Iran J Environ Health Sci Eng 5:283–296Google Scholar
  156. 156.
    Tarley CRT, Kubota LT (2005) Molecularly-imprinted solid phase extraction of catechol from aqueous effluents for its selective determination by differential pulse voltammetry. Anal Chim Acta 548:11–19Google Scholar
  157. 157.
    Santos WDJR, Lima PR, Tarley CRT, Höehr NF, Kubota LT (2009) Synthesis and application of a peroxidase-like molecularly imprinted polymer based on hemin for selective determination of serotonin in blood serum. Anal Chim Acta 631:170–176Google Scholar
  158. 158.
    Koohpaei AR, Shahtaheri SJ, Ganjali MR, Forushani AR, Golbabaei F (2009) Optimization of solid-phase extraction using developed modern sorbent for trace determination of ametryn in environmental matrices. J Hazard Mater 170:1247–1255Google Scholar
  159. 159.
    Valero-Navarro A, Damiani PC, Fernández-Sánchez JF, Segura-Carretero A, Fernández-Gutiérrez A (2009) Chemometric-assisted MIP-optosensing system for the simultaneous determination of monoamine naphthalenes in drinking waters. Talanta 78:57–65Google Scholar
  160. 160.
    Alizadeh T, Ganjali MR, Nourozi P, Zare M (2009) Multivariate optimization of molecularly imprinted polymer solid-phase extraction applied to parathion determination in different water samples. Anal Chim Acta 638:154–161Google Scholar
  161. 161.
    Baggiani C, Anfossi L, Giovannoli C, Tozzi C (2004) Multivariate analysis of the selectivity for a pentachlorophenol-imprinted polymer. J Chromatogr B 804:31–41Google Scholar
  162. 162.
    Rosengren AM, Karlsson JG, Andersson PO, Nicholls IA (2005) Chemometric models of template-molecularly imprinted polymer binding. Anal Chem 77:5700–5705Google Scholar
  163. 163.
    Nantasenamat C, Naenna T, Isarankura-Na-Ayudhya C, Prachayasittikul V (2005) Quantitative prediction of imprinting factor of molecularly imprinted polymers by artificial neural network. J Comput Aided Mol Des 19:509–524Google Scholar
  164. 164.
    Nantasenamat C, Isarankura-Na-Ayudhya C, Naenna T, Prachayasittikul V (2007) Quantitative structure-imprinting factor relationship of molecularly imprinted polymers. Biosens Bioelectron 22:3309–3317Google Scholar
  165. 165.
    Rosengren AM, Golker K, Karlsson JG, Nicholls IA (2009) Dielectric constants are not enough: principal component analysis of the influence of solvent properties on molecularly imprinted polymer-ligand rebinding. Biosens Bioelectron 25:553–557Google Scholar
  166. 166.
    Wythoff BJ (1993) Backpropagation neural networks—a tutorial. Chemom Intell Lab Syst 18:115–155Google Scholar
  167. 167.
    Breneman CM, Thompson TR, Rhem M, Dung M (1995) Electron density modeling of large systems using the transferable atom equivalent method. Comput Chem 19:161–179Google Scholar
  168. 168.
    Bhand SG, Yilmaz E, Danielsson B (2003) Coupled biosensor, biomimetic and chemometrics strategies for analysis of the metals in complex environmental matrices. J Phys IV 107:4Google Scholar
  169. 169.
    Wu X, Carroll WR, Shimizu KD (2008) Stochastic lattice model simulations of molecularly imprinted polymers. Chem Mater 20:4335–4346Google Scholar
  170. 170.
    Veitl M, Schweiger U, Berger ML (1997) Stochastic simulation of ligand-receptor interaction. Comput Biomed Res 30:427–450Google Scholar
  171. 171.
    Nicholls IA, Andersson HS, Charlton C, Henschel H, Karlsson BCG, Karlsson JG, O’Mahony J, Rosengren AM, Rosengren KJ, Wikman S (2009) Theoretical and computational strategies for rational molecularly imprinted polymer design. Biosens Bioelectron 25:543–552Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Ian A. Nicholls
    • 1
    • 2
    Email author
  • Håkan S. Andersson
    • 1
  • Kerstin Golker
    • 1
  • Henning Henschel
    • 1
  • Björn C. G. Karlsson
    • 1
  • Gustaf D. Olsson
    • 1
  • Annika M. Rosengren
    • 1
  • Siamak Shoravi
    • 1
  • Subramanian Suriyanarayanan
    • 1
  • Jesper G. Wiklander
    • 1
  • Susanne Wikman
    • 1
  1. 1.Bioorganic & Biophysical Chemistry Laboratory, Section for Biomaterials and Medicinal Chemistry, School of Natural SciencesLinnaeus UniversityKalmarSweden
  2. 2.Department of Biochemistry and Organic ChemistryUppsala UniversityUppsalaSweden

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