Elsevier

European Polymer Journal

Volume 62, January 2015, Pages 394-399
European Polymer Journal

Alkyne-X modification of polypeptoids

https://doi.org/10.1016/j.eurpolymj.2014.08.028Get rights and content

Highlights

  • Alkyne-X (“click”) chemistry: cyclo, radical, and nucleophilic addition reactions.

  • Modular platform of functionalizable polypeptoids.

  • Synthesis of polypeptoid ionic liquids and graft copolymers.

Abstract

Poly(N-propargyl glycine) (PNPG) can be readily prepared by ring-opening polymerization of N-propargyl glycine N-carboxyanhydride (NCA) and modified using various addition reactions such as copper catalyzed [3+2] cycloaddition of azide, radical (photo-)addition of thiol, nucleophilic addition of ethylene oxide, and thermal induced cross-linking. It is demonstrated that PNPG can serve as a modular platform to produce a bibliography of novel functional polypeptoid or pseudopeptide materials, including polypeptoid ionic liquids and graft copolymers.

Introduction

Having access to well-defined functional polymers, newly referred to as precision polymers, is of great importance for many technical applications but also for basic research. Their synthesis often requires tedious development of new monomeric units and sophisticated polymerization strategies aiming to control molar mass, molar mass distribution, microstructure, architecture, and functionality. Nowadays more flexible and modular polymer platforms are desirable, enabling one to introduce specific functionalities or tailored properties for special applications in reasonable short time scales. In this context, post-polymerization modifications or polymer-analogue reactions (a term going back to Staudinger and Scholz from the early 1930s) [1] have raised much attention; especially since the concept of click chemistry was introduced by Sharpless [2]. Click chemistry includes modular and highly efficient reactions, which have been well established for many decades, like for instance the copper catalyzed azide–alkyne [3+2] cycloaddition, (hetero-) Diels–Alder [4+2] cycloadditions, and thiol–ene/–yne additions [3]. These chemistries allow a mild and efficient incorporation of solubility enhancing groups, functional and targeting moieties (e.g. antibodies, sugars, etc.) to synthetic polymer backbones or biopolymers, which are of particular interest for use in biological applications [4]. Biopolymers, or bio-relevant polymers, include polysaccharides, polypeptides, and pseudopeptides like polypeptoids, i.e. poly(N-substituted glycine)s [5], or polyoxazolines [6]. Polypeptoids are an emerging class of biocompatible materials [7], which are readily available through either solid-phase synthesis [8] or “living” ring-opening polymerization of N-substituted glycine N-carboxyanhydrides (NCAs) [9]. However, very few examples have been reported describing the “click” modification of polypeptoid materials, for instance the photo-addition of thiol to poly(N-allyl glycine) [10] or copper catalyzed addition of azide to poly(N-propargyl glycine) copolymers [11].

Here, we explore the diversity of the alkyne functionality in the chemical modification of poly(N-propargyl glycine) by cyclo, radical, and nucleophilic addition reactions. All polymer products were characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) spectroscopy, and by size exclusion chromatography (SEC).

Section snippets

Chemicals

All chemicals were purchased from commercial sources and used as received (Sigma–Aldrich, ACROS, or Alfa Aesar); methyl 3-bromepropionate (97%), methyl 3-mercaptopropionate (98%), bromoethane (99+%), phosphazene base tBu-P4 (0.8 M solution in hexane), ethylene oxide (99.8%). Anhydrous dichloromethane (DCM), dimethyl sulfoxide (DMSO), and N-methyl-2-pyrrolidone (NMP) were ordered in septum-sealed bottles under dry argon atmosphere over molecular sieves. Acetic anhydride (Ac2O) and benzylamine

Results and discussion

Poly(N-propargyl glycine) (PNPG73, the subscript denoting the number-average degree of polymerization; Mn=7090gmol-1, 1H NMR, Mw/Mnapp=1.3, SEC) was synthesized by primary amine initiated ring-opening polymerization of N-propargyl glycine NCA [9c]. Then, the alkyne side chains were modified as follows: (1) copper catalyzed [3+2] cycloaddition of azide and followed by quaternization of the triazole, (2) thiol–yne radical addition, (3) deprotonation and nucleophilic addition of ethylene oxide,

Conclusions

Poly(N-propargyl glycine) (PNPG) was investigated towards its potential as a platform material for post-polymerization modifications. PNPG was modified using various chemistries such as copper catalyzed [3+2] azide–alkyne cycloaddition (where the triazole linkers were further quaternized to yield a polypeptoid ionic liquid), radical thiol–yne addition, and nucleophilic addition of ethylene oxide. Furthermore, PNPG could be cross-linked by simple thermal treatment to yield an insoluble amorphous

Acknowledgments

Nora Fiedler, Jessica Brandt, Olaf Niemeyer, Marlies Gräwert, and Laurent Chabanne are thanked for their contributions to this work. Financial support was given by the Max Planck Society.

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