Scalable Synthesis of Positively Charged Sequence-Defined Functional Polymers

Synthesizing and characterizing sequence-defined polymers with positively charged backbone are great challenges. By alternately processing Menschutkin reaction and Cu-catalyzed azide-alkyne cycloaddition reaction, we successfully synthesized series of scalable cationic sequence-defined polymers with quaternary ammonium backbone up to 12 repeating units and characterized their precise structures. Due to the dramatic polarity difference between weak polar feed molecules and strong polar target molecules, simple precipitation in weak polar solvents is enough to obtain pure sequence-defined polymers. Such a polar-inverse strategy (PIS), without protecting groups and solid support, offers extremely high yields up to 68% after 12 reaction steps (i.e., average yield >95% for each step), favoring cost-effective large-scale production. Because of the independent reactivity of selected functional groups, the cationic sequence-defined polymers are highly programmable, including backbone composition, sequence order, functional side groups, terminal groups and topological structure. Sequence information decoding is easily achieved according to Maldi-Tof mass spectrum without retrospecting its synthetic history, resulting in a great superiority in the field of information transmitting and reading. The resulting multifunctional sequence-defined polymers are water-soluble and positively charged, opening the avenue to bioapplications such as condensing DNA, gene transfection and drug delivery.