All‐Sequence‐Defined Bottlebrush Polymers via the Passerini Iterative Exponential Growth (P‐IEG)

ABSTRACT

Iterative synthesis of sequence‐defined polymers (SDPs) via multicomponent reactions, such as the Passerini three‐component reaction, can diversify the chemistry and spatial arrangement of the constituting repeating units in the macromolecules with minimal synthetic complexity. Here, we report that the Passerini iterative exponential growth (P‐IEG) method enables control over the chemistry, number, and sequence of all monomers that constitute high‐molecular‐weight bottlebrush polymers (BBPs) and copolymers (BBCPs). Employing uniform polymers and SDPs as isocyanide components, bifunctional backbone building blocks are connected via the Passerini three‐component reaction between aldehyde, carboxylic acid, and isocyanide, which yields uniform BBPs and self‐assembling BBCPs composed of up to 64 backbone repeating units and 63 side chains (a molar mass of up to 63.6 kDa). To demonstrate the ability of P‐IEG to compose the complex sequence of a large library of building blocks, an all‐sequence‐defined bottlebrush polymer (ASD‐BBP) featuring 47 sequence‐defined oligomers (a molecular mass of 50.2 kDa) was successfully synthesized to encode the simple musical score, “Twinkle, Twinkle, Little Star,” into its chemical structure. We suggested that three independent sequences in the polymer backbone, side chains, and side‐chain locations on the backbone could be deciphered using selective backbone immolation without side‐chain degradation.