Hydroxyl Group Tolerated Polymerization of N‑Substituted Glycine <i>N</i>‑Thiocarboxyanhydride Mediated by Aminoalcohols: A Simple Way to α‑Hydroxyl-ω-aminotelechelic Polypeptoids

<i>N</i>-Carboxyanhydride (NCA) polymerization cannot tolerate nucleophilic groups that have the ability of initiation, e.g., hydroxyl group. In contrast, <i>N</i>-thiocarboxyanhydride (NTA) is a much more stable monomer to tolerate them. In this contribution, we investigate aminoalcohols including 2-amino-1-ethanol (<b>AE</b>), 3-amino-1-propanol (<b>AP</b>), 4-amino­methylbenzyl alcohol (<b>AMB</b>), 6-amino-1-hexanol (<b>AH</b>), and 12-amino-1-dodecanol (<b>AD</b>) as initiators for ring-opening polymerization of N-substituted glycine <i>N</i>-thiocarboxyanhydride (NNTA) to prepare α-hydroxyl-ω-aminotelechelic water-soluble polypeptoids. Hydroxyl groups of <b>AE</b>, <b>AP</b>, and <b>AMB</b> are activated by hydrogen bonding with amino groups, which results in a mixture of α,ω-diaminotelechelic and α-hydroxyl-ω-amino­telechelic polypeptoids confirmed by ¹H NMR, MALDI-ToF, and SEC measurements. Pure α-hydroxyl-ω-amino­telechelic polypeptoids are synthesized for the first time initiated by <b>AH</b> and <b>AD</b> with controlled molecular weights (1.3–12.4 kg/mol) and low polydispersity indices (<1.30). Hydroxyl groups in <b>AH</b> and <b>AD</b> remain inactive to generate hydrogen bonding due to the long distance from amino groups. Water-soluble polypeptoids with special functional end groups are attractive alternatives of PEG for their nontoxicity and biocompatibility having great potential in biomedical applications