Theoretical Investigation of the Imprinting Efficiency of Molecularly Imprinted Polymers Simcha Srebnik Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel Received July 30, 2003. Revised Manuscript Received December 29, 2003 Molecular imprinting is an emerging tool for the design of structuredporous materials having a precise arrangement of functional groups within pores of a controlled size and shape. Such controlled specificity in principle can offer a scope of opportunities for molecule- specific recognition applications. In practice, however, molecularrecognition is oftennot fully realized, either due to distortion during the imprinting process or due to incomplete imprinting. Using a mean-field lattice model, we study imprinting efficiency of tetrafunctional monomers using stiff imprinting agents of various sizes and for various preparation conditions. Neglecting imperfections anddistortions duringgelation andpost-treatment, we show that high imprinting efficiencies (i.e., a large number of pores of the needed size and functionality) are hard to achieve. However, monomer-template interactions and preparation conditions can be optimized for a given template size to yield a higher population of high affinity sites. Introduction In the past 2 decades methods for tailoring the structure and chemical affinity of gels have advanced significantly, with particular attention focused on sub- stance-specific recognition-based applications. Molecular imprinting is a technique that was developed to mimic recognition processes in biological systems. The method involves complexation of organicor inorganicfunctional monomers and organic templates (or print molecules), followed by cross-linking of the monomers and subse- quent removal of the templates, thus incorporating molecule-specific binding sites in the gel. Recognition then occurs viaa combination of reversible binding (covalent or polar) and shape complementarity with high affinity and selectivity. In fact, in many cases the technique has proven to be capable of producing materi- als with rebinding affinities and selectivities of the same order of magnitude as commonly observed for antibody- antigen interactions. 1 Applications include analysis and separation of trace levels of compounds, sensors, and enzyme mimics (e.g., refs 2 and 3). In addition, the molecular imprinting technique has beenused to form ordered and structured (usually inorganic) gels (e.g., refs 4-9) Some distinct advantages of molecular imprinting include the simple and rapidpreparation, the stability of the imprinted structures, and the wide variety of substances amenable to imprinting. A notable difficulty with recognition-based applica- tions of molecular imprinting is the low yields of high- affinity sites. The quality and performance of the imprinted gelis clearly affected by the physical and chemical nature of the monomers and templates and the interactions between them,by the polymerization reaction, and by the rebinding ability. Therefore, an understanding of the physics governing the formation of monomer-template complexes is fundamental to a strategic design of imprintedpolymers. Nevertheless, although a rapidly growing field, few efforts have focused on characterizing and understanding the mech- anisms underlying formation and recognition, and even fewer theoretical efforts haveemerged that investigate the interplay of the various parameters influencing the molecular imprinting process. Andersson et al. 10,11 studied theeffect of monomer- template molarratioon the selectivity of the imprinted gel. They found that low ratios result in less than optimal complexation due to insufficient amounts of functional monomers, and selectivity is thus reduced. On the other hand, excess monomer yields a high number of noncomplexed, randomly distributed mono- mers, which contribute to nonspecific binding. They introduced a semiempirical correlation for theestima- tion of the number of selective recognition sites in an imprintedpolymer prepared with a given monomer- template ratio. Mosbach led systematic studies on the (1) Sellergren, B. TrAC, Trends Anal. Chem. 1997, 16, 310. (2) Collinson, M. M. Crit. Rev. Anal. Chem. 1999, 29, 289. (3) Nicholls, I. A.;Adbo, K.;Andersson, H. S.;Andersson, P. O.; Ankarloo, J.; Hedin-Dahlstrom, J.; Jokela, P.; Karlsson, J. G.; Olofsson, L.; Rosengren, J.; Shoravi, S.; Svenson, J.; Wikman, S. Anal. Chim. Acta 2001, 435, 9. (4) Hedrick, J. L.; Miller, R. D.; Hawker, C. J.; Carter, K. R.; Volksen, W.; Yoon, D. Y.; Trollsas, M. Adv. Mater. 1998, 10, 1049. (5) Kramer, E.; Forster, S.; Goltner, C.;Antonietti, M. Langmuir 1998, 14, 2027. (6) Boury, B.; Corriu, R. J. P.; Le Strat, V. Chem. Mater. 1999, 11, 2796. 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