Olof Ramström

The Emerging Technique of Molecular Imprinting and Its Future Impact on Biotechnology

The technique of molecular imprinting allows the formation of specific recognition and catalytic sites in macromolecules by the use of templates. Molecularly imprinted polymers have been applied in an increasing number of applications where molecular binding events are of interest. These include (i) the use of molecularly imprinted polymers as tailor-made separation materials, (ii) antibody and receptor binding site mimics in recognition and assay systems, (iii) enzyme mimics for catalytic applications, and (iv) recognition elements in bio-sensors. The stability and low cost of molecularly imprinted polymers make them advantageous for use in analysis as well as in industrial scale production and application.

MOLECULAR IMPRINTING TECHNOLOGY : CHALLENGES AND PROSPECTS FOR THE FUTURE

Molecular imprinting is a technique for the fabrication of biomimetic polymeric recognition sites or “plastic antibodies/receptors” which is attracting rapidly increasing interest. By this technology, recognition matrices can be prepared which possess high substrate selectivity and specificity. In the development of this technology, several applications have been foreseen in which imprinted materials may be exchanged for natural recognition elements. Thus, molecularly imprinted polymers have been used as antibody/receptor binding mimics in immunoassay-type analyses, as enzyme mimics in catalytic applications and as recognition matrices in biosensors. The best developed application area for imprinted materials, though, has been as stationary phases for chromatography, in general, and chiral chromatography, in particular. This review seeks to highlight some of the more intriguing advantages of the technique as well as pointing out some of the difficulties encountered. The prospects for future development will also be considered. Chirality 10:195–209, 1998.

Synthesis and catalysis by molecularly imprinted materials.

Molecularly imprinted materials have been demonstrated to possess a very high degree of selectivity towards targeted substrates. In addition to such tailor-made molecular recognition, progress has been made in introducing reactive groups into the recognition sites. Putting teeth into imprinted matrices is one method of making true enzyme mimics or plastizymes, which are plastic polymer enzyme mimics.

Insights into the role of the hydrogen bond and hydrophobic effect on recognition in molecularly imprinted polymer synthetic peptide receptor mimics

Abstract Peptide antibody combining site mimics prepared by the molecular imprinting of N-Ac- l -Phe- l -Trp-OMe were used as highly efficient “tailor-made” chiral stationary phases and for the study of non-ionic non-covalent interaction-based recognition. The effect of water on recognition and the role of the hydrogen bonding and the hydrophobic effect on ligand selectivity are discussed.

Synthetic peptide receptor mimics: highly stereoselective recognition in non-covalent molecularly imprinted polymers

Abstract Ligand-receptor recognition has been studied in a molecularly imprinted polymer (MIP) prepared against N -Ac-L-Phe-L-Trp-OMe. The non-ionic non-covalent interaction based recognition was evaluated using the polymers as chiral HPLC stationary phases. Marked regio-, enantio- and diastereo- ligand selectivity were demonstrated with enantiomer separation factors of up to 17.8. The interaction of a series of related structures with the MIP receptor site has provided insight concerning its nature and the recognition mechanisms.

Screening of a combinatorial steroid library using molecularly imprinted polymers

Molecular imprinting is an attractive method for producing highly selective adsorbents, and several new and potentially useful applications based on molecularly imprinted polymers (MIPs) have been described in recent years. In this article, we introduce a new field of application in which the selectivities of imprinted materials can be gainfully employed as binding matrices in the screening of combinatorial libraries. MIPs prepared against androstenone structures could be efficiently employed to select these compounds from a combinatorial library.

Enantiomeric Recognition by Molecularly Imprinted Polymers Using Hydrophobic Interactions

Molecularly imprinted polymers prepared using acrylamide as the hydrogen bonding functional monomer exhibited good enantiomeric recognition properties in aqueous solutions. Our results indicate that the recognition improved with increased mobile phase water percentage and ionic strength, and was also very much pH dependent upon the ionisation properties of the sample molecules. The results can be interpreted in terms of specific hydrophobic interactions between the enantiomeric species and the recognition sites of imprinted polymers. A study of substrate selectivity showed differences between a pure organic system and a water/organic system as the mobile phases. The hydrophobicity of the test compounds was found to be an important parameter in determining the selectivity.

Chiral recognition in adrenergic receptor binding mimics prepared by molecular imprinting.

Molecularly imprinted polymers were prepared against the adrenomimetic agents ephedrine and pseudoephedrine. These compounds each incorporate two chiral centres. The polymers were evaluated with respect to enantiodiscrimination of various adrenergic ligands. The selectivity of the polymeric binding sites for the imprinted molecules was very high, and it was found that binding of both the enantiomeric and diastereomeric isomers of the imprint species were effectively obstructed. In addition, it was found that these polymers could selectively recognize the enantiomers of the endogenous adrenergic ligand epinephrine as well as several β‐adrenergic blockers. These observations suggest that these polymers effectively mimic the recognition patterns exhibited by natural adrenergic receptors.

Chiral recognition by molecularly imprinted polymers in aqueous media

SummaryMolecularly imprinted polymers were prepared using 2-vinylpyridine and/or methacrylic acid as functional monomers in a self-assembly imprinting protocol. The resulting polymers were analyzed in aqueous media, and the effects from the pH of the mobile phase and the degree of added organic solvent were investigated. The results are indicative of the importance of ionic bonds in conjunction with hydrophobic interactions in the formation of the complexes between the analyte and the polymers.

Use of molecularly imprinted polymers in a biotransformation process

Molecularly imprinted polymers are highly stable and can be sterilised, making them ideal for use in biotransformation process. In this communication, we describe a novel application of molecularly imprinted polymers in an enzymatic reaction. The enzymatic condensation of Z-L-aspartic acid with L-phenylalanine methyl ester to give Z-L-Asp-L-Phe-OMe (Z-aspartame) was chosen as a model system to evaluate the applicability of using molecularly imprinted polymers to facilitate product formation. When the product-imprinted polymer is present, a considerable increase (40%) in product yield is obtained. Besides their use to enhance product yields, as demonstrated here, we suggest that imprinted polymers may also find use in the continuous removal of toxic compounds during biochemical reactions.