Polymers prepared using smart templates

Abstract

New molecularly imprinted polymers are described, and a method for their production using novel particle technology based on multifunctional placeholder templates.

1 . A surface imprinted polymer that is obtained by:
 1) providing a multifunctional placeholder template;   2) polymerizing at least one monomer, optionally dissolved in a solvent, in presence of the multifunctional placeholder template;   3) separating the multifunctional placeholder template and polymers adhering to the multifunctional placeholder template from the crude reaction mixture;   4) gradually releasing the polymer adhearing to the multifunctional placeholder template by physical or chemical technique thereby allowing to enrich polymers (MIPs) which bind strongly to the multifunctional template; and   5) reuse of the multifunctional placeholder template repeating steps 1) - 4).   
     
     
         2 . A surface imprinted polymer according to  claim 1 , wherein the multifunctional placeholder template comprises a molecular template connected to an affinity handle, optionally with a spacer therebetween. 
     
     
         3 . A surface imprinted polymer according to  claim 2 , wherein the molecular template comprises a molecular structure representing the target molecule or a fragment of the target molecule. 
     
     
         4 . A surface imprinted polymer according to  claim 2 , wherein the molecular template is selected from the group consisting of peptides, glycans, oligonucleotides, and mimics of oligonucleotides. 
     
     
         5 . A surface imprinted polymer according to  claim 2 , wherein the spacer is sufficiently long for the multifunctional placeholder template to bind the adhered polymer and to the stationary phase. 
     
     
         6 . A surface imprinted polymer according to  claim 2 , wherein the spacer comprises polyethylenglycol, polyglycerol, poly-2-hydroxymethacrylate, or a perfluorinated hydrocarbon chain. 
     
     
         7 . A surface imprinted polymer according to  claim 2 , wherein the spacer is prepared by controlled radical polymerization allowing the molecular template or the affinity handle to be attached by endgroup functionalization 
     
     
         8 . A surface imprinted polymer according to  claim 2 , wherein the affinity handle binds reversibly to functional groups of a solid stationary phase or of one of the phases of a liquid liquid two phase system. 
     
     
         9 . A surface imprinted polymer according to  claim 2 , wherein the affinity handle comprises (i) one or several vicinal diol groups or another functional group capable of reversibly forming ester bonds with a boronic acid ligand, or (ii) a thiol or protected thiol group capable of reversibly binding to a disulfide containing stationary phase. 
     
     
         10 . A surface imprinted polymer according to  claim 2 , wherein the affinity handle is magnetic. 
     
     
         11 . A surface imprinted polymer according to  claim 1 , prepared by a process selected from the group consisting of precipitation polymerization, miniemulsion polymerization, grafting from polymerization, and reversible addition fragmentation chain transfer polymerization (RAFT). 
     
     
         12 . A surface imprinted polymer according to  claim 2 , wherein the separation of the multifunctional placeholder template and polymers adhering to the multifunctional placeholder template from the crude reaction mixture is performed by allowing the crude reaction mixture containing the multifunctional placeholder template to contact a solid stationary phase which is capable of reversibly binding to the affinity handle of the multifunctional placeholder template, thereby leading to separation of the multifunctional placeholder template and particles adhearing to the multifunctional placeholder template from the crude reaction mixture. 
     
     
         13 . A surface imprinted polymer according to  claim 1 , wherein the separation of the multifunctional placeholder template and polymers adhering to the multifunctional placeholder template from the crude reaction mixture is performed by allowing the crude reaction mixture containing the multifunctional placeholder template to be exposed to a magnetic field resulting in magnetic separation of the multifunctional placeholder template and particles adhering to the multifunctional placeholder template from the crude reaction mixture. 
     
     
         14 . A surface imprinted polymer according to  claim 1 , wherein gradually releasing the polymer adhearing to the multifunctional placeholder template is achieved by increasing or reducing temperature. 
     
     
         15 . A surface imprinted polymer according to  claim 1 , wherein gradually releasing the polymer adhearing to the multifunctional placeholder template is achieved by subjecting the separated placeholder template to solutions of increasing ionic strength, organic solvents or organic solvents with modifiers of increasing concentration. 
     
     
         16 . A surface imprinted polymer according to  claim 1 , wherein gradually releasing the polymer adhearing to the multifunctional placeholder template is achieved by subjecting the separated placeholder template to solutions containing an increasing concentration of a displacer molecule. 
     
     
         17 . A surface imprinted polymer according to  claim 1 , containing thiol groups. 
     
     
         18 . A process for the preparation of a molecularly imprinted polymer, comprising:
 1) providing a multifunctional placeholder template;   2) polymerizing at least one monomer, optionally dissolved in a solvent, in presence of the multifunctional placeholder template;   3) separating the multifunctional placeholder template and polymers adhering to the multifunctional placeholder template from the crude reaction mixture;   4) gradually releasing the polymer adhearing to the multifunctional placeholder template by physical or chemical means; and   5) reuse of the multifunctional placeholder template repeating steps 1)-4).   
     
     
         19 . Use of the surface imprinted polymers and/or multifunctional placeholder templates according to  claim 1  (i) in a separation process, (ii) in a sensor for detecting identity and concentration of molecular target(s), (iii) in an assay, (iv) as an in vivo or in vitro imaging or contrast agent, (v) as an electrophoresis detection tool, (vi) as a therapeutic agent, or (vii) as a catalyst. 
     
     
         20 . Use of surface imprinted polymers and/or multifunctional placeholder templates in competitive assays or sensors relying on electrochemical or magnetic detection principles.