Scalable Synthesis of Sequence-Defined, Unimolecular Macromolecules by Flow-IEG

Publication
Proceedings of the National Academy of Sciences of the United States of America 112(34), 10617-10622, DOI: 10.1073/pnas.1508599112

We report a semiautomated synthesis of sequence and architecturally defined, unimolecular macromolecules through a marriage of multistep flow synthesis and iterative exponential growth (Flow-IEG). The Flow-IEG system performs three reactions and an in-line purification in a total residence time of under 10 min, effectively doubling the molecular weight of an oligomeric species in an uninterrupted reaction sequence. Further iterations using the Flow-IEG system enable an exponential increase in molecular weight. Incorporating a variety of monomer structures and branching units provides control over polymer sequence and architecture. The synthesis of a uniform macromolecule with a molecular weight of 4,023 g/mol is demonstrated. The user-friendly nature, scalability, and modularity of Flow-IEG provide a general strategy for the automated synthesis of sequence defined, unimolecular macromolecules. Flow-IEG is thus an enabling tool for theory validation, structure–property studies, and advanced applications in biotechnology and materials science.