Dual‐responsive pegylated polypeptoids with tunable cloud point temperatures

Abstract

A series of pegylated polypeptoids have been readily synthesized by a strategy combining ring‐opening polymerization (ROP) and thiol‐yne photoaddition. The polypeptoids simultaneously incorporated branched oligo(ethylene glycol) (OEG) units and thioether bonds in the side‐chains. All the polypeptoids are readily soluble in aqueous solution and show reversible thermo‐responsive properties. The cloud points (CPs) were demonstrated to be readily tunable in the range of ~25 °C‐60 °C by varying the chemical composition, OEG chain length and the degree of polymerization. Attractively, the chemical compositions of the side chains are readily tunable via adjusting the molar ratios of a mixture of thiol terminated OEG molecules, which avoid synthesizing new monomers or copolymerization of different monomers. Further, the oxidation/reduction of thioether groups shows significant influence on the CPs, providing a second stimulus to tune the phase transition behaviors. Considering the biocompatibility and degradability, the dual‐responsive polypeptoids are potential candidates for various biomedical or biotechnological applications.

Stimulus-Responsive Polymers Based on Polypeptoid Skeletons

“…Li et al showed that the T cp could be adjusted from 25 °C to 60 °C by changing the molecular weight and polymerization degree of OEG unit. At the same time, the thioether bond’s redox property on the side chain of the polymer can also have a more noticeable impact on the T cp of the polymer, thus providing a second stimulus for the regulation of phase transition [ 82 ]. The synthesis of pegylated polypeptoids by photoaddition of mercaptan and alkyne has the disadvantages of inaccurate modification site and low efficiency.…”

Thermoresponsive Polypeptoids

“…Schlaad et al demonstrated the post modifications of poly(N-allyl glycine) (PNAG) and poly(N-propargyl glycine) (PNPgG) through thiol-ene chemistry to introduce various functional groups [45,48]. Sun and coworkers successfully prepared a family of thermoresponsive polypeptoids by combining ROP of NCA and thiol-ene/yne click chemistry [49][50][51]. Zhang et al reported that the cyclic PNPgG homopolymer and copolymer can be modified with azides by CuAAC ( Figure 1) [42].…”

“…Various pegylated polypeptoids can be obtained by adjusting the molar ratios of a mixture of thiol terminated OEG molecules to change the chemical compositions of the pendant side chains. They further synthesized a kind of pegylated polypeptoid that exhibited both reversible thermoresponsive and redox-responsive behaviors in aqueous solution [50]. It was found that the oxidation/reduction of pendant thioethers on the side chain had a great influence on the T cp which providing a second stimulus to tune phase transition behavior.…”

Controlled ring-opening polymerization of N-(3-tert-butoxy-3-oxopropyl) glycine derived N-carboxyanhydrides towards well-defined peptoid-based polyacids

“…16 While propargyl and allyl N-substituents can be further derivatized to install various functional groups on the polypeptoid polymers post-polymerization, the efficiency and extent of derivation vary with the nature of the functional groups and polymer chain length. 13,14,[17][18][19] Thus, it is desirable to design and develop controlled ring-opening polymerization of R-NCA monomers bearing functional N-substituents to enable access to well-defined polypeptoids that have quantitative functional sidechain presence and tailorable polymer chain length.…”