Precise synthesis of thermoresponsive polyvinylphosphonate-biomolecule conjugates via thiol–ene click chemistry1

Abstract

A polymerisation type only recently attracting notice is the rare earth metal-mediated group transfer polymerisation (REM-GTP). This living-type polymerisation is able to conquer the limitations faced by classical anionic and radical polymerisations. REM-GTP enables the synthesis of biocompatible, water-soluble and thermoresponsive polymers with narrow polydispersities and controlled molecular weights. Furthermore, this technique renders the introduction of a functional end-group via the initiating molecule. Our group was able to synthesise a new multi-functional pyridine derivative and apply it as a highly active and efficient initiator in the polymerisation of diethylvinylphosphonate (DEVP). This novel end-group opens the door to various post-polymerisation modifications. In the present study, the thiol–ene click reaction, a fast, selective and well-established coupling method, was applied to link poly-DEVP and a biomolecule. The incentive for this investigation was to create a polymer platform, that can easily address a multiplicity of applications through facile alterations of the coupled biomolecule entities. Herein, we present for the first time the functionalisation of polyvinylphosphonates with biologically relevant motifs, namely cholesterol and folic acid.