Facile Synthesis of Thioether-Functionalized <i>N</i>-Substituted Glycine <i>N</i>-Thiocarboxyanhydride toward Well-Defined Thiopolypeptoids

To synthesize functional polypeptoids, the most straightforward strategy involves designing tailored amino acids to generate corresponding <i>N</i>-substituted glycine <i>N</i>-carboxyanhydrides (NNCAs) or <i>N</i>-substituted glycine <i>N</i>-thiocarboxyanhydrides (NNTAs). An alternative route is offered by postpolymerization modification. However, the potential method of modifying NNCA and NNTA monomers to produce functional polypeptoids has received scant attention. Herein, we employed <i>N</i>-allylglycine <i>N</i>-thiocarboxyanhydride (NAG-NTA) as a versatile platform for the convenient synthesis of thioether-functionalized NNTAs via thiol-ene photoaddition. Controlled polymerizations of these thioether-functionalized NNTAs were achieved in CH₂Cl₂ at room temperature, catalyzed by benzoic acid and initiated by a primary amine, yielding well-defined thiopolypeptoids with relatively low dispersities (<i>Đ</i> < 1.29) and predictable molecular weights. The thermal properties and oxidation responsiveness of the thiopolypeptoids were investigated. Poly(ethylene glycol)-<i>b</i>-thiopolypeptoid self-assembled into micelles in water, whose size and morphologies could be tuned by treatment with H₂O₂, showing promise in the fields of bionics and biomedicine due to their excellent biocompatibility.