MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Biomacromolecules. 2021 Apr 12;22(4):1579-1589. doi: 10.1021/acs.biomac.1c00016. Epub 2021 Mar 30.
Polymerization of -substituted glycine -thiocarboxyanhydrides (NNTAs) is a promising pathway to prepare functional polypeptoids benefiting from their tolerance to nucleophilic impurities. However, controlled NNTA polymerization is hard to achieve in amide polar solvents, including ,-dimethylacetamide (DMAc), ,-dimethylformamide (DMF), and -methyl pyrrolidone (NMP), the only aprotic solvents for many biomacromolecules and polypeptoids. In the present work, we successfully achieve controlled NNTA polymerization in amide polar solvents by adding acetic acid as a promoter. The promotion is applied to the polymerization of sarcosine NTA, -ethyl glycine NTA, and -butyl glycine NTA. DMAc, DMF, and NMP are suitable solvents to prepare polypeptoids with designable molecular weights and low dispersities (1.06-1.21). The polysarcosines with high molecular weights are prepared up to 35.2 kg/mol. A kinetic investigation quantitatively reveals that the presence of acetic acid not only accelerates the polymerization, but also suppresses HS-catalyzed decomposition of NNTAs by decreasing the concentration of HS dissolved in polar solvents. Benzoic acid is also able to promote the polymerization, while trifluoroacetic acid, phosphoric acid, and phenol are not appropriate promoters. The moderate acidity of acids is essential. l-Methionine, l-tryptophan, and l-phenylalanine, which are dissolved in DMF, initiate the controlled polymerization of sarcosine-NTA in the presence of acetic acid and introduce functional end groups to polysarcosines quantitatively. In DMAc, hydrophilic vancomycin is grafted by poly(-butyl glycine). The amphiphilic product dissolves in dichloromethane and stabilizes water-in-oil emulsion.
取代甘氨酸-硫代碳酰亚胺（NNTAs）的聚合是一种很有前途的方法，可以制备功能多肽，因为它们可以耐受亲核杂质。然而，在酰胺极性溶剂中，包括二甲基乙酰胺（DMAc）、二甲基甲酰胺（DMF）和 N-甲基吡咯烷酮（NMP）中，难以实现 NNTAs 的可控聚合，因为它们是许多生物大分子和多肽的唯一非质子溶剂。在本工作中，我们通过添加乙酸作为促进剂，成功地在酰胺极性溶剂中实现了可控的 NNTAs 聚合。该促进剂适用于肌氨酸 NTA、-乙基甘氨酸 NTA 和 -丁基甘氨酸 NTA 的聚合。DMAc、DMF 和 NMP 是适合制备设计分子量和低分散度（1.06-1.21）的多肽的溶剂。高分子量的聚肌氨酸可制备至 35.2 kg/mol。动力学研究定量表明，乙酸的存在不仅加速了聚合反应，而且通过降低溶解在极性溶剂中的 HS 浓度，抑制了 HS 催化的 NNTAs 分解。苯甲酸也能促进聚合，而三氟乙酸、磷酸和苯酚则不是合适的促进剂。酸的适度酸性是必不可少的。在乙酸存在下，溶解在 DMF 中的 l-甲硫氨酸、l-色氨酸和 l-苯丙氨酸可以引发肌氨酸-NTA 的可控聚合，并定量地将功能端基引入聚肌氨酸中。在 DMAc 中，亲水性万古霉素通过聚（-丁基甘氨酸）接枝。该两亲性产物溶解在二氯甲烷中，并稳定油包水乳液。
