High Molecular Weight\nUniform Polymers Encoding Octal\nSequences by Passerini Iterative Exponential Growth

Sequence-defined polymers composed of a large pool of\nchemically\ndistinct monomers (SDPs) have been pursued to achieve the structural\nand functional precisions exhibited by biopolymers in nonbiological\nenvironments. In contrast to the incremental growth of SDPs by sequential\naddition of individual monomers, the iterative exponential growth\n(IEG) method allows the synthesis of high molecular-weight SDPs, but\ntheir sequences have been composed mostly of binary monomers. Consequently,\nachieving high molecular-weight SDPs built with a large pool of monomers\nremains a challenge. Here we report the Passerini iterative exponential\ngrowth (P-IEG) approach that enables efficient synthesis of 128-mer\nuniform poly(hydroxybutyrate) (PHB), possessing 127 γ-acylamino\ncyclohexyl side groups (27 kDa, <i>Đ</i> = 1) and\na 31-mer SDP, encoding an octal sequence composed of eight chemically\ndistinct repeating units. Taking advantage of the combinatorial character\nof the Passerini three-component reaction involving an aldehyde, a\ncarboxylic acid, and an isocyanide to form an acyloxy amide linkage,\nwe simultaneously achieved the exponential chain growth through the\nconvergence of bifunctional building blocks and side-chain implementation\nby selecting appropriate isocyanides as a third component. The P-IEG\napproach enabled the synthetic encoding of complex information, an\noctal sequence equivalent to a 93-bit binary code, into a 31-mer SDP.\nOur proposed P-IEG method could contribute to the synthesis of synthetic\nmacromolecules with absolutely defined sequences of functionalities.\nThese polymers could be used for the development of functional materials\nwith properties not achievable by conventional polymers, including\npolymers storing digital information at higher density.