Encoding Nucleobase Sequences to Synthetic Polyesters Using Adenine/Thymine-Containing Isocyanides as Gluing Components for the Passerini IEG.

DNA exhibits programmable self-assembly through complementary hydrogen bonding between nucleobases introduced to sugar-phosphate backbones in defined sequences, inspiring the development of synthetic analogs with nucleobases as recognition motifs. However, most nucleobase-containing polymers lack defined monomer sequences or molecular uniformity, limiting their biomimetic precision. In this work, we synthesized sequence-defined polymers bearing adenine and thymine units via a Passerini iterative exponential growth strategy. Butoxycarbonyl (Boc)-protected nucleobase-functionalized isocyanides were employed to construct poly(hydroxybutyrate) bearing butyl- and bp-thymine side chains and poly(hydroxybutyrate) with butyl- and bp-adenine side chains with uniform molecular weights. After Boc deprotection, NMR analyses revealed complementary adenine-thymine hydrogen bonding, showing characteristic downfield shifts in a 1:1 mixture, an association constant of 320 M-1 obtained by NMR titration, and thermoreversible behavior in variable-temperature NMR experiments. Furthermore, adenine and thymine were incorporated into a single polymer backbone, demonstrating the method's ability to encode programmable hydrogen-bonding motifs into uniform synthetic macromolecules.