Utilising α-picoline-borane for the reductive amination of dextran: synthesis of polysaccharide block copolymers by...

Polysaccharide block copolymers are often prepared by functionalisation at the polysaccharide reducing end using toxic reducing agents such as NaCNBH₃, before incorporation of a second polymer block. Herein we report the synthesis of a polysaccharide (dextran) macromolecular chain transfer agent (macro-CTA) using the non-toxic reducing agent α-picoline-borane (pic-BH₃). The reductive amination reaction conditions of dextran (M_r ≈ 6000 g/mol), Dex_6K, with benzylamine were optimised with conversions up to ~96%, validating the suitability of pic-BH₃. Reaction with fluoresceinamine confirmed the use of pic-BH₃ for selective labelling at the reducing chain-end, characterised by UV-Vis spectroscopy and UV-Vis SEC analyses. When preparing a dextran macro-CTA, a diamine was used, followed by esterification with 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid, yielding Dex_6K-RAFT. Novel double-hydrophilic block copolymers were synthesised by chain extending Dex_6K-RAFT with poly(ethylene glycol) methyl ether methacrylate (POEGMEM) by aqueous reversible addition-fragmentation chain-transfer (RAFT) solution polymerisation, targeting degrees of polymerisation between 50 and 200. High conversions were obtained (95-97%) after 6 h, with aqueous SEC analyses confirming successful chain extension. This work demonstrates pic-BH₃ as a non-toxic reducing agent for the aqueous chain end functionalisation of polysaccharides by reductive amination, and previously unexplored double hydrophilic Dex_6K-b-POEGMEM block copolymers, enabling safer, greener syntheses for the development of advanced polysaccharide-based materials.