Efficient One‐Pot Synthesis of Water‐Compatible Molecularly Imprinted Polymer Microspheres by Facile RAFT Precipitation Polymerization

Abstract

Molecular imprinting is a versatile and straightforward method for the preparation of polymer receptors with tailor-made recognition sites. Despite the tremendous progress made in this field, many challenges still remain to be addressed. In particular, it has been shown that the presently developed molecularly imprinted polymers (MIPs) are normally only organic solvent compatible and they mostly fail to show specific template bindings in pure aqueous solutions, thus significantly limiting their practical applications in the field of biotechnology. Although some approaches, which either use specifically designed functional monomers or apply the conventional imprinting protocol, have been developed for the preparation of MIPs with molecular recognition ability under aqueous conditions, versatile approaches for the preparation of MIPs that are applicable in pure aqueous environments are still rare. Herein, we report a new and efficient one-pot approach to obtain pure-water-compatible and narrowly dispersed MIP microspheres with surface-grafted hydrophilic polymer brushes by facile reversible addition/fragmentation chaintransfer (RAFT) precipitation polymerization (RAFTPP), mediated by hydrophilic macromolecular chain-transfer agents (Macro-CTAs; Scheme 1). The presence of hydrophilic polymer brushes on MIP microspheres significantly improved their surface hydrophilicity and dramatically reduced their hydrophobic interactions with template molecules in pure aqueous media, thus leading to their water compatibility. The easy availability of many different hydrophilic Macro-CTAs (by either RAFT polymerization of hydrophilic monomers or hydrophilic polymer end group modification), together with the versatility of RAFTPP for the controlled preparation of MIP microspheres, makes this strategy highly applicable for the design of hydrophilic and water-compatible MIPs. Two strategies have been developed for the synthesis of water-compatibleMIPs by improving their surface hydrophilicity; these strategies involve the use of a hydrophilic comonomer, functional monomer, or crosslinker in the molecular imprinting process, and the postmodification of the preformed MIPs. Although simple in principle, the former strategy either requires time-consuming optimization of MIP formulation components or can only be applied in some special systems. In comparison, the latter strategy, which involves the surface grafting of hydrophilic polymer layers, has proven highly attractive because it not only significantly improves the MIPs surface hydrophilicity, but also provides a protective layer to prevent protein molecules from blocking their imprinting sites in biological solutions. Very recently, we have successfully prepared pure-water-compatible MIP microspheres by the controlled grafting of hydrophilic polymer layers onto the preformed MIP particles. Compared with this two-step approach, the new strategy presented herein allows the more efficient controlled synthesis of pure-water-compatible MIP microspheres with surface-grafted hydrophilic polymer brushes by a one-pot RAFTPP method. To show proof-of-principle for our strategy, a model noncovalent molecular imprinting system was chosen because Scheme 1. Chemical structures of the utilized RAFT agents (including hydrophilic Macro-CTAs and CDB) and the schematic protocol for the one-pot preparation of water-compatible MIP microspheres by RAFT precipitation polymerization.