Radical Ring-Opening Single Unit Monomer Insertion: An Approach to Degradable and Biocompatible Sequence-Defined Oligomers

Sequence-defined polymers prepared from vinyl monomers attract tremendous research interests in mimicking the precise primary sequence and remarkable biological functions of natural biopolymers. Sequential single unit monomer insertion (SUMI) via the reversible addition–fragmentation chain-transfer (RAFT) mechanism shows the ability to assemble vinyl monomers in defined orders efficiently with high yields. However, the approach of RAFT SUMI to produce both degradable and biocompatible sequence-defined oligomers has not been reported yet. In this research, we report the radical ring-opening SUMI of a cyclic ketene acetal monomer, 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), with the alternating insertion of N-substituted maleimides to afford sequence-defined oligomers. The oligomers can be degraded into shorter fragments due to the ester bonds incorporated in the backbone. Moreover, one prepared trimer demonstrates the biocompatibility to the investigated human normal cells while showing the cytotoxic effect against the studied human cancer cells. The properties of the produced oligomers endowed by BMDO hold promise for decoding information stored in sequence-defined polymers and the potential in biomedical applications.