Histidine <italic style="font-style: italic">N</italic>-Thiocarboxyanhydride: Direct Synthesis and Polymerization without Protection towards Well-defined Polyhistidine

Song-Yi Xu; Tian-Wen Bai; Bo-Tuo Zheng; Ze-Hua Li; Jun Ling

doi:10.1007/s10118-025-3348-0

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Histidine N-Thiocarboxyanhydride: Direct Synthesis and Polymerization without Protection towards Well-defined Polyhistidine

RESEARCH ARTICLE | Updated：2025-07-26

- Histidine N-Thiocarboxyanhydride: Direct Synthesis and Polymerization without Protection towards Well-defined Polyhistidine
- Histidine N-Thiocarboxyanhydride: Direct Synthesis and Polymerization without Protection towards Well-defined Polyhistidine
- 高分子科学（英文） 2025年43卷第8期页码：1311-1319
- Affiliations：
  
  a.MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China
  b.College of Biological, Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314001, China
  c.College of Chemistry and Materials Science, Fujian Key Laboratory of Polymer Materials, Fujian Normal University, Fuzhou 350007, China
- Author bio：
  
  lingjun@zju.edu.cn
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 22271252 and 22201105). We thank Prof. Xufeng Ni, Dr. Peng Zhou, and Mr. Yixuan Mei from Testing and Analysis Center of Department of Polymer Science and Engineering, Zhejiang University, for the MALDI-ToF measurements.;Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-025-3348-0.
- DOI：10.1007/s10118-025-3348-0
  中图分类号：
- 收稿：2025-02-24，
  
  修回：2025-03-16，
  
  录用：2025-03-31，
  
  网络首发：2025-05-26，
  
  纸质出版：2025-08-01
- Accepted：
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Xu, S. Y.; Bai, T. W.; Zheng, B. T.; Li, Z. H.; Ling, J. Histidine N-thiocarboxyanhydride: direct synthesis and polymerization without protection towards well-defined polyhistidine. Chinese J. Polym. Sci. 2025, 43, 1311–1319

Song-Yi Xu, Tian-Wen Bai, Bo-Tuo Zheng, et al. Histidine N-Thiocarboxyanhydride: Direct Synthesis and Polymerization without Protection towards Well-defined Polyhistidine[J]. Chinese Journal of Polymer Science, 2025, 43(8): 1311-1319. DOI: 10.1007/s10118-025-3348-0.
Xu, S. Y.; Bai, T. W.; Zheng, B. T.; Li, Z. H.; Ling, J. Histidine N-thiocarboxyanhydride: direct synthesis and polymerization without protection towards well-defined polyhistidine. Chinese J. Polym. Sci. 2025, 43, 1311–1319 DOI： 10.1007/s10118-025-3348-0.

Song-Yi Xu, Tian-Wen Bai, Bo-Tuo Zheng, et al. Histidine N-Thiocarboxyanhydride: Direct Synthesis and Polymerization without Protection towards Well-defined Polyhistidine[J]. Chinese Journal of Polymer Science, 2025, 43(8): 1311-1319. DOI: 10.1007/s10118-025-3348-0. DOI：

摘要

In the contribution

Histidine N-thiocarboxyanhydride (His-NTA) is synthesized bearing unprotected imidazole group directly in basic aqueous solution. Controlled polymerization of His-NTA is performed using organic acid as designed ionic temporary protection for unprotected imidazole group

with discovery and explanation of equilibria-controlled polymerization mechanism.

Abstract

Consisting of natural histidine residues

polyhistidine (PHis) simulates functional proteins. Traditional approaches towards PHis require the protection of imidazole groups before monomer synthesis and polymerization to prevent degradation and side reactions. In the contribution

histidine

-thiocarboxyanhydride (His-NTA) is directly synthesized in aqueous solution without protection. With the self-catalysis of the imidazole side group

the ring-closing reaction to form His-NTA does not r

equire any activating reagent (

e.g.

phosphorus tribromide)

which is elucidated by density functional theory (DFT) calculations. His-NTA directly polymerizes into PHis bearing unprotected imidazole groups with designable molecular weights (4.2−7.7 kg/mol) and low dispersities (1.10−1.19). Kinetic experiments and Monte Carlo simulations reveal the elementary reactions and the relationship between the conversion of His-NTA and time during polymerization. Block copolymerization of His-NTA with sarcosine

-thiocarboxyanhydride (Sar-NTA) demonstrate versatile construction of functional polypept(o)ides. The triblock copoly(amino acid) PHis-

-PSar-

-PHis is capable to reversibly coordinate with transition metal ions (Fe

and Zn

) to form pH-sensitive hydrogels.

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Keywords

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Histidine N-Thiocarboxyanhydride: Direct Synthesis and Polymerization without Protection towards Well-defined Polyhistidine

Histidine N-Thiocarboxyanhydride: Direct Synthesis and Polymerization without Protection towards Well-defined Polyhistidine

DOI：10.1007/s10118-025-3348-0

摘要

Abstract

关键词

Keywords

references