Well-Defined Biological Sample-Compatible Molecularly Imprinted Polymer Microspheres By Thiol-Epoxy Coupling Chemistry And Study On Their Properties

Molecularly imprinted polymer(MIP),as a synthetic receptor with specific recognitionability for template molecules,has become a hot research topic because of its high affinity,good stability,easy preparation and low cost.MIPs capable of selectively recognizing small organic analytes in complex biological samples hold great promise in many bioanalytical and biomedical applications,but development of such advanced synthetic receptors remains a challenging task.The aim of this work mainly focuses on the following two points:(1)developing a facile and efficient new strategy based on thiol–epoxy coupling chemistry for obtaining well-defined hydrophilic MIP microspheres capable of selectively recognizing small organic analytes in complex biological samples;and(2)demonstrating whether or not the hydrophilic MIPs obtained by the ring-opening of surface epoxy groups on MIP particles are compatible with biological samples.The specific research results are as follows.(1)Its proof-of-principle has been demonstrated by the first synthesis of “living”propranolol-imprinted polymer microspheres via reversible addition-fragmentation chain transfer(RAFT)precipitation polymerization(RAFTPP),their grafting of a thin crosslinked polymer shell with surface epoxy groups via the surface-initiated RAFT polymerization,and subsequent thiol-epoxy “click” coupling reaction between the resulting MIP microspheres with surface epoxy groups and a hydrophilic macromolecular thiol(i.e.,thiol-terminated poly(2-hydroxyethyl methacrylate)(PHEMA-SH)).The successive RAFTPP and surface-initiated RAFT polymerization readily led to MIP microspheres with surface epoxygroups(MIP-EP)and good propranolol recognition ability in the organic solvent(but not in the aqueous solution).The “click” coupling reaction between PHEMA-SH and epoxy groups on MIP-EP largely enhanced their surface hydrophilicity and transformed such waterincompatible MIP particles into biological sample-compatible ones.This work provides a new way to develop biocompatible MIP microspheres.(2)The simple ring-opening of the epoxy groups on MIP-EP by using perchloric acid(following a previously reported method to obtaining water-compatible MIPs)only provided MIPs with propranolol recognition ability in pure water instead of in the complex biological sample.