Accelerated and parallel synthesis of sequence-defined polymers is an utmost challenge for realizing ultrahigh-density storage of digital information in molecular media. Here, we report step-economical synthesis of sequence-defined poly( l -lactic- co -glycolic acid)s (PLGAs) using continuous flow chemistry. A reactor performed the programmed coupling of the 2-bit storing building blocks to generate a library of their permutations in a single continuous flow, followed by their sequential convergences to a sequence-defined PLGA storing 64 bits in four successive flows. We demonstrate that a bitmap image (896 bits) can be encoded and decoded in 14 PLGAs using only a fraction of the time required for an equivalent synthesis by conventional batch processes. Accelerated synthesis of sequence-defined polymers could also contribute to macromolecular engineering with precision comparable to natural precedents.

Sequence-defined synthetic oligomers and polymers are promising molecular media for permanently storing digital information. However, the information decoding process relies on degradative sequencing methods such as mass spectrometry, which consumes the information-storing polymers upon decoding. Here, we demonstrate the nondestructive decoding of sequence-defined oligomers of enantiopure α-hydroxy acids, oligo( l -mandelic- co - d -phenyl lactic acid)s (oMPs), and oligo( l -lactic- co -glycolic acid)s (oLGs) by 13 C nuclear magnetic resonance spectroscopy. We were able to nondestructively decode a bitmap image (192 bits) encoded using a library of 12 equimolar mixtures of an 8-bit-storing oMP and oLG, synthesized through semiautomated flow chemistry in less than 1% of the reaction time required for the repetition of conventional batch reactions. Our results highlight the potential of bundles of sequence-defined oligomers as efficient media for encoding and decoding large-scale information based on the automation of their synthesis and nondestructive sequencing processes.

Polyesters exhibiting a protein-like absolute atomic precision have unlimited potential for application as biomaterials and polymeric materials. Herein, we report the synthesis of enantiomeric ω-hydroxy acids (OHAs) from terminal epoxides and alkenes as starting materials. Our synthetic strategy allows the synthesis of a library of OHAs with a well-defined atomic composition (carbon number), stereochemical configuration, and substituent chemistry. These monomers can serve as building blocks for the preparation of discrete and sequence-defined polyesters, wherein various functional groups can be introduced at specific locations via the cross-convergent method. We demonstrated that the specific locations of the reactive functional groups of the sequence-defined polyester could be utilized to form a concentrically cyclic polymer upon cyclization. Our results provide a facile platform for engineering polyesters with the structural sophistication exhibited only by biopolymers, such as proteins and nucleic acids.