Molecularly imprinted polymers Presentation in Sensors, Arrays, Screening Lennart Niehues, Jan Philip Meyer 1
Overview Introduction Advantages Disadvantages Theory of MIP Requirements for the optimal MIP Properties of the optimal MIP Applications Summary References 2
Introduction What are molecularly imprinted polymers (MIP)? A polymer which is formed in the presence of a target molecule A template (e.g. Tamoxifen) is used for structural assembly of the polymer The polymer is build up by functional monomers (e.g. 4 vinylpyridine) 3
Introduction 4
Advantages Cost effective alternative to biomolecule based recognition Ease of preparation; enhanced chemical and thermal stability Can be prepared in different formats; eg: bead, block, thin film Can be stored for years without loss of affinity for target molecule 5
Disadvantages Lower catalytic capabilities than biological counterparts Binding site heterogeneity providing a distribution of binding site affinities Template bleeding requires suitable templates analogue for the imprinting step and effects quantitative applications 6
Theory of MIP Recognition mechanism has to be understood in detail! Until now it is not, as the following example will demonstrate 7
Theory of MIP The molecular recognition is based on non covalent interactions: H bonds π π (stacking) interactions Van der Waals interactions Ionic interactions 8
Requirements for the optimal MIP Requirements for the optimal selectivity on molecular recognition Structural criteria Best compromise between: Rigidity, flexibility and optimal cavity shape Chemical criteria Complementarity of interactions of the involved molecules 9
Requirements for the optimal MIP It has been observed that the reoccupation is very low It was shown that the forming of stable complexes in the pre polymerization solution are quite low Only 0,5 1% of the theoretical binding site yields can be classified as medium to high affinity binding sites 10
Requirements for the optimal MIP Discovery methods for the development of MIP s with enhanced recognition properties: 2 approaches to the optimal MIP 1. Combinatorial Chemistry 2. Molecular Modelling 11
Requirements for the optimal MIP 1. Combinatorial Chemistry approach Parallel multiplexed MIP preparation and testing using split mix synthesis followed by in situ analysis 2. Molecular Modelling approach Determing the optimal MIP by calculated screening of different potential monomers 12
Requirements for the optimal MIP Example for a molecular modelling approach 13
Properties of the optimal MIP High chemical stability against acids and bases, as well as high temperatures (up to 150 C) Size limitations: templates with a relatively low molecular weight Solution: Recognition of epitopes of large template molecules (proteins, antigenes) 14
Applications Molecularly imprinted sold phase extration (MIPSE) Sensor recognition elements Enantioselective materials for pharmaceutical industry Enzyme linked MIP sorbent assays 15
Applications 16
Applications MIPSE Selective extration method, can be done in homogeneous solution (LLE) and heterogeneous solution (LC) Focus on different molecular interactions: Ion exchange, H bonding, hydrophobicity etc. But! After 4 th assay decrease of separation ability 17
Applications acutal situation Two companies: ELIPSA (Germany) and MIP Technologies (Sweden) Main goal of the companies is to extract molecules from biological matrices MIP materials claim up to 3% of the separation market, with an increasing outlook 18
Summary MIP offers a great opportunity to separate biological relevant molecules with high selectivity in a cheap and non biological way (ph, T) For a greater success the tunability and knowledge of the mechanisms have to improved with the mentioned tuning approaches 19
References J.O.Mahoney, Anal. Chim. Ac. 2005, 534, 31 39. G.Wulff, Angew. Chem. Int. Ed. 1995, 34, 1812 1821. K.Haupt, Chem. Rev. 2002, 202, 1 43. http://www.miptechnologies.com/ 20