N-substituted glycine N-thiocarboxyanhydrides (NTAs) are alternative monomers to prepare polypeptoids with large-scale producing potential compared to the corresponding N-carboxyanhydrides (NCAs) due to their easily synthetic approach and stability during purification and storage. Novel monomer N-butylglycine NTA (NBG-NTA) has been synthesized and well characterized for the first time. Rare earth borohydrides [RE(BH 4 ) 3 (THF) 3 , RE = Sc, Y, La, Nd, Dy, and Lu] have been first applied in the polymerization of sarcosine NTA (Sar-NTA) and NBG-NTA to achieve high molecular weight (MW) hydrophilic and hydrophobic polypeptoids. Polysarcosines (PSars), poly(N-butylglycine)s (PNBGs), and their copolymers with high yields, high MWs, and moderate MW distributions are synthesized at 60 °C by using RE(BH 4 ) 3 (THF) 3 initiators. MWs of polypeptoids are controlled by feed molar ratios. For instance, PSar with an absolute M n of 27.7 kDa (DP = 390) and PDI of 1.14 is produced successfully from Sar-NTA. Thermoresponsive random copolypeptoids poly(sarcosine-r-N-butylglycine)s [P(Sar-r-NBG)s] have reversible phase transitions (cloud point temperature) in aqueous solution and minimal cytotoxicity comparable to PEG and PSar, which is promising in various biomedical and biotechnological applications. Thermal properties of homo-and co-polypeptoids are investigated by TGA and DSC measurements.

N-substituted glycine N-thiocarboxyanhydrides (NTAs) are alternative monomers for preparing polypeptoids. With an easy synthetic approach and stability during purification and storage, they have much more potential for mass production than the corresponding N-carboxyanhydrides (NCAs). Thermoresponsive copolypeptoids are synthesized by copolymerization of sarcosine NTA (Sar-NTA) with N-butylglycine NTA (NBG-NTA) initiated by benzylamine in THF at 60°C. Polypeptoids with a degree of polymerization over 150 are obtained for the first time through primary amine-initiated NTA polymerizations. The molecular weights (MWs) and compositions of poly(sarcosine-r-N-butylglycine)s [P(Sar-r-NBG)s] are controlled by the feed molar ratios of [Sar]/[NBG]/[benzylamine]. The thermal behaviors of the copolypeptoids are investigated. Reactivity ratios of Sar-NTA and NBG-NTA are determined as 1.70(7) and 0.63(7), indicating a random distribution of the two monomers in the polypeptoid products. The structure and precise amino chain end of P(Sar-r-NBG) are confirmed by MALDI-ToF mass analysis. P(Sar-r-NBG)s have lower critical solution temperatures (LCST) and exhibit reversible phase transitions in aqueous solution. Their cloud point temperatures (T cp s) are tunable between 27 and 71°C by adjusting the sarcosine molar fraction in copolymers. In addition, T cp transitions depend on the MWs and the concentrations of the polypeptoids,as well as salt additives, to a certain degree. A biocompatibility study on P(Sar-r-NBG) reveals a controlled cytotoxicity related to the composition of polypeptoids. Easily accessible from NTA polymerizations, polypeptoids are therefore novel degradable materials with LCST for biomedical applications. † Electronic supplementary information (ESI) available. See

Amino acid N-thiocarboxyanhydride (NTA), the thioanalog of N-carboxyanhydride (NCA), is much more stable than NCA against moisture and heat. The convenient monomer synthesis without rigorous anhydrous requirements makes the ring-opening polymerization of NTA a competitive alternative to prepare polypeptoid-containing materials with potential of large-scale production. Polysarcosines (PSars) with high yields (>90%) and low polydispersities (<1.2) are synthesized from sarcosine N-thiocarboxyanhydride (Sar-NTA) at 60 °C initiated by primary amines including poly(ethylene glycol) amine (PEG-NH2 ). The lengths of PSar segments are controlled by various feed ratios of Sar-NTA to initiator. PEG-b-PSar products, a class of novel double-hydrophilic diblock copolymers, are effective in stabilizing oil-in-water emulsions at nano- and microscale, which demonstrates promising encapsulation applications in food, cosmetics, and drug delivery. Due to the different solubility of PEG and PSar blocks, PEG-b-PSar copolymers form micelles in organic solvents with the capability to incorporate metal cations including Cu(2+) and Ni(2+) .

N-Substituted glycine N-thiocarboxyanhydrides (NNTAs) are promising cyclic monomers to synthesize polypeptoids with the advantages of easier preparation and higher stability during purification and storage than N-substituted glycine N-carboxyanhydrides (NNCAs). NNTAs were commonly considered too stable to polymerize for their low reactivity. In this contribution, we report controlled polymerizations of N-ethylglycine NTA (NEG-NTA) and sarcosine NTA (Sar-NTA) using primary amines as initiator under proper polymerization conditions. The controllability has been fully supported by 1 H NMR end group analyses, MALDI-ToF mass spectra, kinetic data, block copolymerizations by sequential monomer addition, and low polydispersities (1.14-1.17) of polypeptoids. Variation of the [NNTA]/[initiator] ratio allows well control of the molar mass, and degrees of polymerization (DPs) up to 287 can be reached for poly (N-ethylglycine) or DPs up to 262 for polysarcosine. NNTAs exhibit excellent activity and they are potential to synthesize polypeptoids with controllable polymerization.