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A generic SDM synthesis strategy is reported now using a support-free orthogonal approach starting from single monomers to produce SDMs. The procedure does not require any support, protection, or deprotection steps, nor does it require solvent switches. Crucially, each reaction step is followed by purification using solvent-resistant nanofiltration to ensure product retention from the reaction mixture with the complete removal of impurities (excess reagents, catalyst, byproducts). The sharp molecular weight resolution of well-tuned epoxy-based membranes renders this strategy highly efficient and versatile, as proven here by applying varying reactions, monomer types, and sizes to prepare two different sequence-defined conjugated macromolecules (SDCMs). Demonstrating the effectiveness of these membrane separations to purify SDCMs across very diverse conditions thus highlights the transformative potential of advanced membrane technology for SDM synthesis. Overall, a robust foundation is provided for advancing SDM development from single monomers to complex, high-purity oligomers.<\/jats:p>","DOI":"10.1021\/prechem.5c00409","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T10:33:50Z","timestamp":1775212430000},"page":"1386-1394","source":"Crossref","is-referenced-by-count":0,"title":["A Support-Free Strategy to Synthesize Sequence-Defined\nMacromolecules Using Solvent-Resistant Nanofiltration"],"prefix":"10.1021","volume":"4","author":[{"given":"Zahra","family":"Bozorgmehr","sequence":"first","affiliation":[{"name":"KU Leuven , , Celestijnenlaan 200F, Box 2454 , ,","place":["Leuven, Belgium, 3001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Peeters","sequence":"additional","affiliation":[{"name":"KU Leuven , , Celestijnenlaan 200F, Box 2404 , ,","place":["Leuven, Belgium, 3001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wout","family":"Milis","sequence":"additional","affiliation":[{"name":"KU Leuven , , Celestijnenlaan 200F, Box 2404 , ,","place":["Leuven, Belgium, 3001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1809-3722","authenticated-orcid":true,"given":"Laurens A. 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Sci."},{"key":"2026092808075353500_cit36","doi-asserted-by":"publisher","DOI":"10.1016\/j.seppur.2025.134762","article-title":"Filtration\nperformance and surface morphology of epoxy-based (TFC) membranes\nsynthesized in various solvent systems","volume":"378","author":"Bozorgmehr","year":"2025","journal-title":"Sep.\nPurif. Technol."},{"key":"2026092808075353500_cit37","unstructured":"Open Membrane\nDatabase. OMD4SRNF: OSN Data and Analysis Tools."},{"issue":"1","key":"2026092808075353500_cit38","first-page":"14","article-title":"Separation of polyphenolics\nand sugar\nby ultrafiltration: Effects of operating conditions on fouling and\ndiafiltration","volume":"1","author":"Wei","year":"2008","journal-title":"Int. J. Chem. Biomol. 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