1,1,3,3-Tetramethylguanidine mediated ring-opening polymerization of N-butyl N-carboxyanhydride monomers using alcohol initiators The ring-opening polymerization (ROP) of N-carboxyanhydrides (NCA) to access polypeptoids can follow a normal primary amine mechanism. Accessing new, hybrid materials such as heteroblock copolymers may require modification of a moiety to one that can initiate ROP. Hydroxyl groups are commonly observed in nature and hydroxyl initiation can avert a modification step but alcohols are not nucleophilic enough to initiate ROP alone. Tetramethylguanidine (TMG) was investigated as an organocatalyst to improve alcohol nucleophilicity via hydrogen-bonding interactions in the ROP of N-Bu NCA, a model monomer. Using a benzyl alcohol initiator with TMG (0.06 mol. % relative to [M]0), polypeptoids ranging from 2.9 – 20.5 kg∙mol-1 with adequate PDI values (1.02 – 1.23) were obtained. Polymerization activity was observed to decrease in more sterically hindered alcohols (iPrOH, t-BuOH), limiting the system’s universality. Macroinitiation using a PEG-OH initiator was found to be successful in generating heteroblock copolypeptoids. Scheme 1. ROP with alcohol and TMG promotor A B C D Figure 1. (A) Plot of Mn (black) and PDI (red) versus conversion % for a polymerization using BnOH initiator. ([M]0:[BnOH]0=50:1; (B) SEC chromatograms for enchainment experiment; (C) Kinetic plot of ln[M]0/[M] versus reaction time for a series of polymerizations with BnOH initiator; (D) Plot of kobs obtained from (C) versus [BnOH]0. Brandon Chan