Synthesis of α,ω-heterotelechelic PVP for bioconjugation, via a one-pot orthogonal end-group modification procedure

Abstract

A simple one pot orthogonal procedure for synthesizing α-aldehyde, ω-thiol heterotelechelic poly(N-vinylpyrrolidone) (PVP) is introduced. Firstly we designed a xanthate chain transfer agent with an acetal protected aldehyde functionality in the leaving group, then we synthesized α-acetal ω-xanthate end-functional PVP, via a RAFT-mediated polymerization. The end-groups were modified via a facile, modular protocol, by first aminolysing the ω-xanthate end-groups to form thiols, using an excess of a primary amine, and subsequently acidifying the reaction medium to simultaneously convert excess primary amine to its (non-interfering) quaternary ammonium salt form, as well as effect the acid-catalysed deprotection of the acetal into an aldehyde functionality, to access the α-aldehyde, ω-thiol-PVP. Finally, we demonstrated the utility of these end-groups by performing conjugations with model small molecules. This study establishes a facile procedure for accessing different and bio-relevant end-functional groups with a biocompatible vinyl polymer, suitable for making drug delivery vehicles.