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Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10617-22. doi: 10.1073/pnas.1508599112. Epub 2015 Aug 12.

Scalable synthesis of sequence-defined, unimolecular macromolecules by Flow-IEG.

Author information

1
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
2
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 jaj2109@mit.edu tfj@mit.edu.

Abstract

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.

KEYWORDS:

automation; continuous flow chemistry; polymers; sequence-controlled polymers; unimolecular macromolecules

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