Ring-Opening Polymerization of N-Carboxyanhydrides for Preparation of Polypeptides and Polypeptide-Based Hybrid Materials with Various Molecular Architectures

Abstract

Different synthetic approaches utilizing ring-opening polymerization of N-carboxyanhydrides for preparation of polypeptide and polypeptide-based hybrid materials with various molecular architectures are described. An overview of polymerization mechanisms using conventional (various amines) as well as some recently developed initiators (hexamethyldisilazane, N-heterocyclic persistent carbenes, etc.) is presented, and their benefits and drawbacks for preparation of polypeptides with well-defined chain lengths and chain-end functionality are discussed. Recent examples from literature are used to illustrate different possibilities for synthesis of pure polypeptide materials with different molecular architectures bearing various functional groups, which are introduced either by modification of amino acids, before they are transformed into corresponding Ncarboxyanhydrides, or by post-polymerization modifications using protective groups and/or orthogonal functional groups. Different approaches for preparation of polypeptide-based hybrid materials are discussed as well using examples from recent literature. Syntheses of simple block copolymers or copolymers with more complex molecular architectures (graft and star copolymers) as well as modifications of nanoparticles and other surfaces with polypeptides are described.

50th Anniversary Perspective: Polymers with Complex Architectures

“…Besides the biodegradability/biocompatibility of polyesters/polyethers and the many biomedical applications, the major impact of polymer chemists, in their effort to mimic Nature, is the synthesis of polypeptides. Usually the polymerization is carried out via the ring opening of α-amino acid N -carboxy­anhydrides (NCAs) using mainly primary amines as initiators, under inert or high-vacuum conditions. − The intensive interest in peptide-based polymers steams from their ability to bear several functionalities and to form high order structures, mimicking the Natural relative proteins . Since the synthesis of linear polypeptides is reported by comprehensive reviews and books, − in this Perspective we will only focus on the synthesis of polypeptides via ROP of NCAs with complex macromolecular architectures.…”

“…49−52 The intensive interest in peptide-based polymers steams from their ability to bear several functionalities and to form high order structures, mimicking the Natural relative proteins. 53 Since the synthesis of linear polypeptides is reported by comprehensive reviews and books, 54−57 in this Perspective we will only focus on the synthesis of polypeptides via ROP of NCAs with complex macromolecular architectures.…”