MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering , Zhejiang University , Hangzhou 310027 , China.
Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering , East China University of Science and Technology , Shanghai 200237 , China.
Biomacromolecules. 2018 Nov 12;19(11):4263-4269. doi: 10.1021/acs.biomac.8b01119. Epub 2018 Oct 16.
Polypeptoids are noticeable biological materials due to their versatile properties and various applications in drug delivery, surface modification, self-assembly, etc. N-Substituted glycine N-thiocarboxyanhydrides (NNTAs) are more stable monomers than the corresponding N-carboxyanhydrides (NNCAs) and enable one to prepare polypeptoids via ring-opening polymerization even in the presence of water. However, larger amounts of water (>10,000 ppm) cause inhibition of the polymerization. Herein, we discover that during polymerization hydrogen sulfide evolves from the hydrolysis of carbonyl sulfide, which is the byproduct of ring-opening reaction, and reacts with NNTA to produce cyclic oligopeptoids. The capture of N-ethylethanethioic acid as an intermediate product confirms the reaction mechanism together with density functional theory quantum computational results. By bubbling the polymerization solution with argon, the side reaction can be suppressed to allow the synthesis of polysarcosine with high molar mass ( M = 11,200 g/mol, Đ = 1.25) even in the presence of ∼10,000 ppm of water.
聚肽类似物因其多功能特性和在药物传递、表面修饰、自组装等方面的各种应用而备受关注。N-取代甘氨酸 N-硫代碳酰亚胺（NNTAs）比相应的 N-碳酰亚胺（NNCAs）更稳定，即使在存在水的情况下，也能通过开环聚合来制备聚肽类似物。然而，更多的水（>10,000 ppm）会抑制聚合反应。在此，我们发现聚合过程中，羰基硫的水解会产生硫化氢，这是开环反应的副产物，它会与 NNTA 反应生成环状寡肽类似物。捕获 N-乙基乙硫代酸作为中间产物，结合密度泛函理论量子计算结果，共同证实了这一反应机理。通过将聚合溶液用氩气鼓泡，可以抑制副反应，从而在存在约 10,000 ppm 水的情况下，仍能合成具有高分子量（M=11,200 g/mol，Đ=1.25）的聚肌氨酸。
