Integrated Synthesis and Purification of Chemically Diverse Abiotic Sequence-Defined Macromolecules via Solvent-Resistant Nanofiltration

Abiotic sequence-defined macromolecules (SDMs) offer unique opportunities for precision molecular design, yet their broader adoption and utilization remain limited by the lack of general and efficient workflows that unify iterative synthesis and purification across chemically diverse structures. Here we report a platform that combines soluble-support SDM growth with solvent-resistant nanofiltration (SRNF) and demonstrate its implementation within multiple synthesis protocols. The reaction and purification steps are performed in a single solvent and reactor, enabling high membrane flux and operational simplicity. All SDMs are synthesized on uniform soluble supports bearing cleavable linkers and long alkyl chains, ensuring efficient membrane retention and broad applicability. The platform is validated for thiolactone-, oligo(amide)-, and oligo(carbamate)-based SDMs, including hydrophilic, hydrophobic, and amphiphilic structures. In addition, a bidirectional growth strategy compatible with the same purification methodology reduces the number of reaction steps and accelerates the SDM preparation. Overall, this work establishes a robust, automation-compatible approach for integrated abiotic SDM synthesis and purification, enabling efficient access to chemically diverse sequence-defined macromolecular structures.