Direct N-substituted N-thiocarboxyanhydride polymerization towards polypeptoids bearing unprotected carboxyl groups

Botuo Zheng; Tianwen Bai; Jun Ling; Jihong Sun

doi:10.1038/s42004-020-00393-y

Direct N-substituted N-thiocarboxyanhydride polymerization towards polypeptoids bearing unprotected carboxyl groups

Commun Chem. 2020 Oct 28;3(1):144. doi: 10.1038/s42004-020-00393-y.

Authors

Botuo Zheng^{1

2}, Tianwen Bai², Jun Ling³, Jihong Sun^{4

5}

Affiliations

¹ Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
² MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
³ MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China. lingjun@zju.edu.cn.
⁴ Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China. sunjihong@zju.edu.cn.
⁵ Innovation Center for Minimally Invasive Techniques and Devices, Zhejiang University, Hangzhou, 310016, China. sunjihong@zju.edu.cn.

Abstract

Synthesis of poly(α-amino acid)s bearing carboxyl groups is a critical pathway to prepare biomaterials to simulate functional proteins. The traditional approaches call for carboxyl-protected monomers to prevent degradation of monomers or wrong linkage. In this contribution, we synthesize N-carboxypentyl glycine N-thiocarboxyanhydride (CPG-NTA) and iminodiacetic acid N-thiocarboxyanhydride (IDA-NTA) without protection. Initiated by amines, CPG-NTA directly polymerizes into polyCPG bearing unprotected carboxyl groups with controlled molecular weight (2.8-9.3 kg mol^-1) and low dispersities (1.08-1.12). Block and random copolymerizations of CPG-NTA with N-ethyl glycine N-thiocarboxyanhydride (NEG-NTA) demonstrate its versatile construction of complicated polypeptoids. On the contrary, IDA-NTA transforms amines into cyclic IDA dimer-capped species with carboxyl end group in decent yields (>89%) regio-selectively. Density functional theory calculation elucidates that IDA repeating unit is prone to cyclize to be the six-membered ring product with low ΔG. The polymer is a good adhesive reagent to various materials with adhesive strength of 33-229 kPa.

Abstract

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