Lithium hexamethyldisilazide initiated superfast ring opening polymerization of alpha-amino acid N-carboxyanhydrides

Abstract

Polypeptides have broad applications and can be prepared via ring-opening polymerization of α-amino acid N-carboxyanhydrides (NCAs). Conventional initiators, such as primary amines, give slow NCA polymerization, which requires multiple days to reach completion and can result in substantial side reactions, especially for very reactive NCAs. Moreover, current NCA polymerizations are very sensitive to moisture and must typically be conducted in a glove box. Here we show that lithium hexamethyldisilazide (LiHMDS) initiates an extremely rapid NCA polymerization process that is completed within minutes or hours and can be conducted in an open vessel. Polypeptides with variable chain length (DP = 20–1294) and narrow molecular weight distribution (Mw/Mn = 1.08–1.28) were readily prepared with this approach. Mechanistic studies support an anionic ring opening polymerization mechanism. This living NCA polymerization method allowed rapid synthesis of polypeptide libraries for high-throughput functional screening.

Enzyme-mimetic self-catalyzed polymerization of polypeptide helices

“…After the 2-h polymerization in DCM, the end-group analysis showed <1% loss of terminal amine groups 19 , indicating negligible chain termination 10,12 . In addition, owing to the fast polymerization kinetics and the water-immiscibility of DCM 20,21 , the polymerization of NCA in DCM in the presence of 10 vol% water still resulted in well-defined polypeptide with predictable MW, similar to that obtained under anhydrous conditions (Fig. 2d and Supplementary Table 1).…”

Aqueous Ring‐Opening Polymerization‐Induced Self‐Assembly (ROPISA) of N‐Carboxyanhydrides

“…demonstrated that removal of CO 2 by a N 2 flow during polymerization of γ‐benzyl‐ l ‐glutamate N ‐carboxyanhydrides (BLG‐NCA) produced polypeptides with predictable molar masses and narrow distributions . Similar advances are achieved using ultrafast new ROP initiators, such as triethylaminetriamine (TREN) or LiHMDS . The latter initiator is particularly suitable as the polymerization is performed in an open‐air vessel despite NCA moisture sensitivity .…”

“…Similar advances are achieved using ultrafast new ROP initiators, such as triethylaminetriamine (TREN) or LiHMDS . The latter initiator is particularly suitable as the polymerization is performed in an open‐air vessel despite NCA moisture sensitivity . Finally, Cheng et al.…”

Dealing with the Foreign‐Body Response to Implanted Biomaterials: Strategies and Applications of New Materials

“…Polypeptides are widely used in the fields of life science and biomaterials owing to their superior biocompatibility and diversified functions. [ 282,283 ] In recent decades, peptides with antifouling properties have also been discovered and used for sundry applications such as biosensors. [ 242 ] Woll et al.…”