Primary ammonium/tertiary amine-mediated controlled ring opening polymerisation of amino acid N-carboxyanhydrides.

TL;DR: Stable commercial primary ammonium chlorides were combined with tertiary amines to initiate the controlled ring opening polymerisation of amino acid N-carboxyanhydrides to yield polypeptides with defined end group structure, predetermined molar mass and narrow molarmass distribution.

About: This article is published in Chemical Communications.The article was published on 2015-10-15 and is currently open access. It has received 43 citations till now. The article focuses on the topics: Tertiary amine & Molar mass distribution.

Summary

Summary

• Stable commercial primary ammonium chlorides were combined with tertiary amines to initiate the controlled ring opening polymerisation of amino acid N-carboxyanhydrides to yield polypeptides with defined end group structure, predetermined molar mass and narrow molar mass distribution.
• Achieving good control over polymerisation reactions is essential for the synthesis of well-defined polymers.
• Typically, anionic, cationic, controlled radical and ring opening polymerisation (ROP) techniques are applied to synthesise polymers with predetermined composition, functionality, molar mass, and low dispersity.
• These properties are essential in the fields of selfassembly and biomimicry.
• Self-assembled and biomimetic supramolecular assemblies, such as micelles, vesicles, hydrogels and hierarchical scaffolds, are often developed for biomedical or materials science applications. [2] [3] [4] [5] [6] [7].
• Polypeptides are very interesting polymers, not only because they can be designed to be biocompatible and biodegradable, but also because they can be synthesised in a controlled manner by ROP of amino acid N-carboxyanhydrides (NCAs).
• 8, 9 The non-metal catalysed ROP of NCAs is known to proceed via two distinct pathways, namely the normal amine mechanism (NAM) and the activated monomer mechanism (AMM) (Scheme 1a and b).
• 10 The NAM is favoured by the use of nucleophilic initiators such as primary amines and yields welldefined polypeptides.
• The AMM is favoured by bases, such as tertiary amines, and yields polypeptides with high molar mass and dispersity.
• It is challenging to completely suppress the AMM.
• Over the past two decades, considerable advances in controlled NCA polymerisation have been realised.

Figures

Fig. 4 Time-conversion plots for the polymerisations of (a) BLG–NCA (100 equiv.) and (b) LLeu–NCA (100 equiv.) in DMF initiated by BnA HCl (1 equiv.), BnA HCl/TEA (1 : 0.5 equiv.), BnA (1 equiv.), and TEA (0.5 equiv.). Monomer conversions were determined by FT-IR spectroscopy (see ESI†); numbers in (a) are the polymer dispersities determined by SEC.

Fig. 3 Polymerisation of BLG–NCA (150 equiv.) in DMF initiated by PyA HCl/TEA (1 : 0.5 equiv.), paused at 24 h by adding HCl and resumed at 81 h by adding TEA. (a) time-conversion plot, (b) number-average molar mass and dispersities (at 24 h, 81 h, 120 h, and 168 h) determined by SEC.

Fig. 2 SEC traces (RI in black, UV340nm in purple) of polymerisations of BLG–NCA (150 equiv.) in DMF initiated by (a) PyA HCl/TEA (1 : 1.1) at (top to bottom) 2 h, 6 h, 10 h, 24 h; (b) PyA HCl/TEA (1 : 1.5) at (top to bottom) 2 h, 6 h, 8 h, 24 h; the peak (*) is a high molar mass polystyrene (PS2M, 2 MDa) used as internal standard for calculating the monomer conversion (ESI†).

Fig. 1 SEC traces of PBLGs obtained during the polymerisations of BLG–NCA (150 equiv.) in DMF initiated by (a) TAB 3HCl (1 equiv.), r.t.; (b) TAB 3HCl (1 equiv.), 50 1C; (c) TAB 3HCl/TEA (1 : 0.5 equiv.), r.t.; and (d) TEA (0.5 equiv.), r.t.; the peak (*) is a high molar mass polystyrene (PS2M; 2 MDa) used as internal standard for calculating the monomer conversion (ESI†).