Ring-Opening Polymerization of N-Carboxyanhydrides Initiated by a Hydroxyl Group

We report on a method for preparation of well-defined synthetic polypeptides by ring-opening polymerization (ROP) of alpha-amino acid N-carboxyanhydrides (NCA) initiated by a hydroxyl group. To overcome the issue of slow initiation by hydroxyl group, an acid catalyst was used in the initiation step to catalyze opening of the NCA ring by the hydroxyl group and to simultaneously suppress further chain propagation by protonation of the formed amine group. In this way, we have separated slow initiation from the fast chain propagation, since such a combination leads to poorly defined products, and instead performed them in a successive manner. Only after completion of the initiation, the propagation was started by the addition of a base to deprotonate the ammonium group. This method was successfully applied for the synthesis of homopolypeptides by using alcohol as an initiator as well as polypeptide-based block copolymers by using poly(ethylene glycol) or poly(styrene) macroinitiator terminated with the hydroxyl group. This approach not only expands the pool of possible initiators, but also significantly facilities the preparation of polypeptide-based hybrid polymers.