16-7-分子印迹

MolecularImprintingPolymersMIPsIntroductionInchemistry,molecularimprintingisatechniquetocreatetemplate-shapedcavitiesinpolymermatriceswithmemoryofthetemplatemolecules.SchematicofmolecularimprintingTemplateassembly(binding)Templateacb1-addcross-linker2-polymerise(inporogenicsolvent)Templatere-bindingtemplateremovalrecognitionsiteHistoryofMolecularImprintingMolecularimprintingwasusedasearlyasthe1930'sbyMVPolyakovtoselectivelycapturevariousadditivesinasilicamatrix.Inthe1940'sLinusPaulinghypothesizedthataprocesssimilartomolecularimprintingcouldberesponsiblefortheselectivityofantibodiestotheirrespectiveantigens.BiologicalsystemsMolecularrecognitionplaysanimportantroleinbiologicalsystemsandisobservedinbetweenreceptor-ligand,antigen-antibody,DNA-protein,sugar-lectin,RNA-ribosome,etcAntigensAntigenAntigen-bindingsiteHistoryofMolecularImprintingTheconceptofmolecularimprintingwasrevivedinthe1970'swhenGünterWulffdiscoveredthathighlycrosslinkedorganicpolymerscouldalsobeusedtomakemolecularimprintswithhighspecificity.Inmorerecentyears,imprintedpolymershavebeenusedtocaptureeverythingfromsteroidstoTNT.ImprintingmethodologiesCovalentReversiblecovalentlinkageOHOHR1R2+BR3HOHOOBOR1R2R3-2H2O+2H2OMolecularImprinting:CovalentOOOOOOHBBOOOOOOHBBOHHOOHOHBBOOOOpolymerize-galactose+galactoseWulff&SchauhoffJ.Org.Chem.,1991,56,395-400.ImprintingmethodologiesadvantagesanddisadvantagesCovalentImprintingAbilitytofixtemplateinplaceduringpolymerisation-lowerdispersityinbindingsitesCanbecarriedoutinanysolventflexibilityCanbedifficulttoremovetemplatefrompolymer-lowrecoveryofvaluabletemplatesandlownumberofbindingsitesLimitednumberofchemistriesforfixingtemplatetopolymerreversibly-reductioninnumberoftemplatesthatcanbeimprintedPoorkineticsofre-bindingImprintingmethodologiesNon-covalentMonomer-templatecomplexes+R1OOHNR3R2R1OOHR2R3NMolecularImprinting:Non-covalentOOHOOHCH3OOOOHNNHH3CHNHOOOOHHOOCH3OOOOHNNHH3CHNOOHHOOOHOHOOOOHEGDMA,polymerizeNon-covalenttemplate-monomercomplexImprintisspatiallyandfunctionallycomplemetarytotemplateRamströmet.al.Tetrahedron:Asymmetry,1994,5,649-656.Imprintingmethodologies-advantagesanddisadvantagesNon-covalentimprintingEasytoremovetemplatefrompolymer-goodrecoveryofvaluabletemplatesandaccessiblebindingsitesVerylargenumberoftemplatesamenabletonon-covalentimprintingRapidkineticsofre-bindingInabilitytofixtemplateinplaceduringpolymerisation-polydispersityinbindingsites,poordefinitionGenerallyrequireslow-polarityaproticsolvents-incompatiblewithaqueouspolymerisationsImprintingmethodologiesSacrificialspacer(semi-covalent)CovalentlinkduringsynthesisNon-covalentrebindingR1R2OOOR1OOClR2OH+R1OHHOR2MolecularImprinting:SpacerApproachOOOOOOOHOHOHOOOOAIBN,65oC,24h1MNaOH/MeOHrefluxCholesterolinn-hexaneWhitcombeetal.J.Am.Chem.Soc.,1995,117,7105-7111.CVPCImprintingmethodologies-advantagesanddisadvantagesSacrificialspacermethodAbilitytofixtemplateinplaceduringpolymerisation-lowerdispersityinbindingsitesCanbecarriedoutinanysolventflexibilityRapidkineticsofre-bindingCanbedifficulttoremovetemplatefrompolymer-lowrecoveryofvaluabletemplatesandlownumberofbindingsitesLimitednumberofchemistriesforfixingtemplatetopolymerreversibly-reductioninnumberoftemplatesthatcanbeimprintedTargetmolecules&ImprintingmatricesTargetmoleculesSmallorganicmolecules:,pesticides,aminoacids,nucleotidebases,steroids,sugars,metalionpeptides,proteinsanddrug,…ImprintingmatricesAcrylicandvinylpolymersOrganicpolymersOtherimprintingmatricesPreparationMIPsGenerallyMIPshavebeenpreparedasmonolithsusing‘bulk’polymerizationofvinylicmonomermixturesbyfreeradicalinitiation;Consequently,thematerialrequiresgrindingbeforeuse(sievingisoftenalsoemployedtofractionatebyparticlesize)PreparationMIPsInsitupolymerization.InordertoavoidthegrindingandpackingofHPLCcolumnsthepolymerisformedinsideacolumnasaporousmonolith.Coatedsilicaparticles.Apolymerizablegroupwasfirstattachedtothesilicasurfaceandpolymerizationwasthencarriedoutusingtemplate,cross-linkerandfunctionalmonomer.Molecularimprintingoftheophyllineimmobilizedontoasolidsupport:immobilizedtemplatewithmonomers(1),compositematerialafterpolymerization(2),imprintedpolymerafterdissolutionofthesupport.1231PreparationMIPsPrecipitationpolymerization.Precipitationpolymerizationcanbeperformedwithsimilarprepolymerizationmixturesasforbulkpolymers,exceptthattherelativeamountofsolventpresentinthemixtureismuchhigher.Whenpolymerizationprogresses,imprintednano-ormicrospheresprecipitateinsteadofpolymerizingtogethertoformapolymermonolith.PreparationMIPsW/Oemulsionpolymerization.Bindingsitesconfinedattheinteriorsurfaceofvoidswithinanorganicpolymercanbecreatedbypolymerizationofthecontinuous(oil)phaseofawater-in-oil(W/O)emulsionstabilizedwithanamphiphilicfunctionalsurfactantcomplexedwiththetemplatemoleculeatthewater–oilinterface.and…ApplicationsofimprintedpolymersSeparationChromatographyCapillaryelectrochromatographySolidphaseextractionPseudoimmunoassaysSynthesis&CatalysisSensorsSeparation:chromatographyMIPsassta