1,1,3,3-Tetramethylguanidine-Mediated Zwitterionic Ring-Opening Polymerization of Sarcosine-Derived N-Thiocarboxyanhydride toward Well-Defined Polysarcosine

Abstract

Zwitterionic ring-opening polymerization (ZROP) of sarcosine-derived N- thiocarboxyanhydrides (Me-NNTAs) can be induced by using 1,1,3,3-tetramethylguanidine (TMG) initiators in CH 2 Cl 2 at 25 °C, rapidly producing well-defined polysarcosine polymers with controlled molecular weights ( M n = 1.9–37 kg/mol) and narrow molecular weight distributions ( Đ = 1.01–1.12). The reaction exhibits characteristics of a living polymerization, evidenced by pseudo-first-order polymerization kinetics, the linear increase of polymer molecular weight ( M n ) with conversion, and the successful chain extension experiments. The polymerization is proposed to proceed via propagating macro-zwitterions bearing a cationic 1,1,3,3-tetramethylguanidinium and an anionic thiocarbamate chain end. The TMG not only initiates the polymerization but also serves to stabilize the thiocarbamate chain end where the monomer addition occurs. Because of the enhanced hydrolytic stability of Me-NNTA, the polymerization can be conducted without the rigorous exclusion of moisture, further enhancing the appeal of the method to access well-defined polysarcosine.

Efficient Synthesis of N-Methyl Polypeptides by Organic Acid Promoted Controlled Ring-Opening Polymerization of N-Methyl-α-Amino Acids N-Carboxyanhydrides

“…When a carboxylic acid/TMG (or carboxylic acid/benzylamine) mixture was used as the initiator, both the nucleophilic carboxylate and TMG (or benzylamine) possibly served as the initiator. Actually, polymers with TMG end group were indeed observed in the previously reported work if TMG alone was used as the initiator . Moreover, if the monomer was initiated by the carboxylate to form an anhydride end group which was replaced by the benzylamine through nucleophilic substitution, then a polymer with a carboxylate end group should be observed in the ROP with high concentration of AA (e.g., [M] 0 /[BnNH 2 ] 0 /[AA] 0 = 25:1:25) since the benzylamine should be in the salt form and unlikely to attack the anhydride.…”

“…Actually, polymers with TMG end group were indeed observed in the previously reported work if TMG alone was used as the initiator. 37 Moreover, if the monomer was initiated by the carboxylate to form an anhydride end group which was replaced by the benzylamine through nucleophilic substitution, then a polymer with a carboxylate end group should be observed in the ROP with high concentration of AA (e.g., [M] 0 /[BnNH 2 ] 0 /[AA] 0 = 25:1:25) since the benzylamine should be in the salt form and unlikely to attack the anhydride. In fact, only polymer with benzylamine end group was observed regardless of the concentration of AA.…”

A Field Guide to Optimizing Peptoid Synthesis

“…However, there is minimal control over the chain ends of the polypeptoids using this strategy and molecular weight plateauing was still observed at high DPs. 1,1,3,3-Tetramethylguanidine (TMG) was used to initiate the ROP of methyl-NNTAs by Zhang and co-workers, producing well-defined polypeptoids with no plateauing observed for monomer to initiator ratios up to 400:1 and predictable chain ends (Figure B) . A novel peptoid synthetic method inspired by the controlled, living polymerization of NCAs with transition-metal catalysts was created by Kramer and Clauss to produce chain-length controlled polypeptoids with functionalized end groups (Figure B) .…”

“…1,1,3,3-Tetramethylguanidine (TMG) was used to initiate the ROP of methyl-NNTAs by Zhang and co-workers, producing well-defined polypeptoids with no plateauing observed for monomer to initiator ratios up to 400:1 and predictable chain ends (Figure 3B). 82 A novel peptoid synthetic method inspired by the controlled, living polymerization of NCAs with transitionmetal catalysts was created by Kramer and Clauss to produce chain-length controlled polypeptoids with functionalized end groups (Figure 3B). 75 Using nickel amido-amidate preformed catalysts, the ROP of NNCAs yielded polypeptoids with excellent control over chain lengths for a variety of hydrophilic and hydrophobic side chains.…”

Research Progress in Polypeptoids Prepared by Controlled Ring‐Opening Polymerizations

“…[ 51 ] A recent study, however, demonstrated that Me‐NTA can undergo zwitterionic ring‐opening polymerization (ZROP) in CH 2 Cl 2 at 25 °C using 1,1,3,3‐tetramethylguanidine (TMG) as the initiator to obtain well‐defined polysarcosine with controlled MW and narrow MW distribution. [ 52 ] The polymerization rate of Me‐NTA using the TMG initiator is nearly two‐fold faster than using the benzylamine initiator. This is attributed to the stable propagating macro‐zwitterion of positively charged guanidinium and negatively charged thiocarbamate ends.…”