Enzyme accelerates reactions with large tolerance, high specificity and remarkable efficiency. To translate the enzymatic property for the synthetic analogue is of great interest to obtain a high quality catalyst. Indeed, the artificial enzyme has gained significant progress in recent years. For example low molecular weight substances were used as artificial enzyme, such as, cyclodextrin,1 cucurbituril,2 synthetic cavitands.3 Those compounds are used as molecular hosts to provide well-defined binding site with functionalized catalytic groups for specific substrates. The other category of artificial enzyme is synthetic polymeric substances. 4The advantages of synthetic polymeric substances include not only the high stability against heat, chemicals and solvents, but also their complicated three-dimensional structures that could mimic the real enzyme. The cooperative features, such as the induce fit, the steric strain and the allosteric effect are related to the polymeric enzymatic nature.5 Synthetic polymers have been used as enzyme mimics to catalyze varieties of reactions.6-7 Based on the previous literature, in order to create a synthetic polymeric artificial enzyme with catalytic activity, there are certain prerequisites.12 First of all, there should be a binding cavity that has a shape resembles the shape of the substrate or, even better, the shape of the transition state. Meanwhile, the binding site has to contain coenzyme analogues or catalytic groups that are located in a favorable orientation for the catalysis to occur. In addition to the above two categories, metal-directed macrocycle is another well studied area for highly efficient catalysis. Example includes self-assembled molecular square for catalyst carrier. 8

Among polymer based artificial enzymes, molecular imprinted polymer (MIP) is one of the systems that can fulfill the above principles well. Molecular imprinting has been a long tradition of constructing synthetic analogue in biomimetic recognition, 9-10 molecular sensing, 11 catalysis,12 separation of compounds,13-14 drug delivery.15 The technique starts with the formation of a crosslinked polymer around a template molecule in the presence of cross linkers. The functional monomer in the monomer mixture can interact with the template through covalent or noncovalent interaction. After removing the template, the predetermined imprint can be left behind. This imprint containing functional groups in a certain orientation is sterically and electronically complementary to the template. Molecular imprinting makes it possible to design catalytic binding site against any molecule of interest in theory.16 Enzyme-like MIPs have been made for selected catalysis.17-18

However, the traditional MIPs have the disadvantage of insolubility and heterogeneity of the active site which need to be improved in order to be widely used in biological systems. Therefore, the molecularly imprinted nanogel was created.19-20 But the binding selectivity and catalytic selectivity are limited due to the less rigid structures of MIP nanogels. The reasons could come from the weak hydrophobic interaction between the functional monomer and the template during the imprinting process in the nonpolar solvent. Our research group reported a method to form molecularly imprinted cross-linked micelle and its use in forming the receptors for bile salt derivatives,21 aromatic carboxylates and sulfonates,22 nonsteroidal anti-inflammatory drugs (NSAIDs)23 and peptides.24 These molecularly imprinted nanoparticles (MINPs) are fully water-soluble and have enzyme-like structure.25

Aside from the solubility, another important point in optimizing the catalytic imprinted polymers is the design of the binding interaction between the functional groups and the template. The covalent/stoichiometric method ensures a more reliable imprinting in making the pocket. Wulff and coworkers have made crucial breakthroughs.26 But the synthesis of the template is relatively complicated due to the requirement of forming a cleavable bond to vacate the binding pocket. Typical methods used are involving boronate esters,27 ketals/acetals,28 and Schiff’s base.29 Another drawback is that the removal of the template is pretty difficult in order to completely remove the template. The noncovalent method, mainly exits in biology interactions, doesn’t require as complicated synthesis as it is in covalent method for no reversible bond is needed. Plus, the template is easier to be split compare to the covalent imprinting. The group of Mosbach and coworkers have done lots of great work with noncovalent binding.30 However, noncovalent interaction (ionic interactions, hydrogen bonding, van der Waals forces and ᴫ- ᴫ interactions) is relatively weak, especially in the presence of polar solvent, such as water and DMF. Therefore, the association constant for the template reuptake is rather low because of the unsuccessful imprinting process in aqueous environment.12 In this dissertation, I present several ways of forming the catalytic active site in our cross linked micelle for making the artificial esterase.