Combining RAFT and staudinger ligation: A potentially new synthetic tool for bioconjugate formation

Article abstract of DOI:10.1021/ma2000724

We report a new route for biocompatible polymer end-group modification by means of the Staudinger ligation. This reaction allows the formation of a peptide bond in aqueous media between a phosphine-containing ester functionality and an azide group. Esterification of the two carboxylic acid-containing chain transfer agents (CTAs), 2-(dodecylsulfanylthiocarbonylsulfanyl)-2- methylpropionic acid (1) and 4-cyano-4-(dodecylsulfanylthiocarbonylsulfanyl) pentanoic acid (2), with different appropriate phosphines gave phosphine-containing CTAs. They allowed us to synthesize polystyrene of medium molecular weight via "reversible addition-fragmentation chain transfer" (RAFT) polymerization. 3,6,9-Trioxodecyl azide (TOD-N ₃) was then used as model compound to study the Staudinger ligation with the corresponding polymers. Among all CTAs tested, the phosphine- functionalized CTA-4, prepared from 2 and P-borane-(diphenylphosphanyl) methanethiol (6), not only proved to be suitable for RAFT polymerization of styrene but the polymer-bound P-borane-(diphenylphosphanyl)methyl thioester group also showed the best performance in the subsequent polymer analogous Staudinger ligation.