Development of Sequence‐Controlled, Degradable, and Cytocompatible Oligomers with Explicit Fragmentation Pathways

Abstract

Sequence‐defined and degradable polymers can mimic biopolymers, such as peptides and DNA, to undertake life‐supporting functions in a chemical way. The design and development of well‐structured oligomers/polymers is the most concern for the public, even to further uncover their degradation process illustrating the degraded products and their properties. However, seldom investigation has been reported on the aforementioned aspects. In this work, the alternating photo‐reversible addition‐fragmentation chain‐transfer (photo‐RAFT) single unit monomer insertion (SUMI) of different N‐substituted maleimides and thermal radical ring‐opening SUMI of a cyclic ketene acetal monomer (i.e., 5,6‐benzo‐2‐methylene‐1,3‐dioxepane (BMDO)) is adopted, to produce two degradable pentamers owing to the conversion of the exo‐methylene group of BMDO into ester bonds along the main chains of the prepared products. Moreover, the possible degraded approach of pentamers is studied by combining high‐resolution mass spectrometry (HRMS) and liquid chromatography‐mass spectrometry (LC‐MS) for the first time. This work also sheds light on the precise structures and cytotoxicity of SUMI products and their degraded compounds, proposing a detailed and credible outlook for biomedical applications.

Solid-phase synthesis of iterative RAFT single unit monomer insertion adducts

“…To that end, we opted to use a PET-RAFT SUMI methodology which has been extensively investigated by our group and others, with thermal analogues having been investigated previously too. 17,[21][22][23][33][34][35][36] In order to translate PET-RAFT processes to solid-phase synthesis, we required the reaction to be run in solvents other than DMSO, due to its inability to swell polystyrene resins. 37 To this end, we applied recent work in which an additional radical scavenger, ascorbic acid, allowed us to perform PET-RAFT SUMI under ZnTPP catalysis, in DMF solvent.…”

Pyrazole carbodithiolate-driven iterative RAFT single-additions

“…15,16 Similarly, the Xiao group has developed the iterative SUMI of cyclic ketene acetals. 17,18 The You group have even used the RAFT SUMI chemistry of polyfunctional-maleimides for stepgrowth polymerisations. 19,20 From these developments, it remains a challenge to iterate these SUMI processes indefinitely while maintaining the aforementioned selectivity.…”

“…15,16 Similarly, the Xiao group has developed the iterative SUMI of cyclic ketene acetals. 17,18 The You group have even used the RAFT SUMI chemistry of polyfunctional-maleimides for step-growth polymerisations. 19,20…”