Nondestructive Sequencing of Enantiopure Oligoesters by Nuclear Magnetic Resonance Spectroscopy

Abstract

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.

Reading Information Stored in Synthetic Macromolecules

“…Despite the fact that nowadays almost every organic or polymer chemistry lab has routine access to an NMR facility, there have been very few studies that solely rely on this technique for the sequence elucidation of synthetic macromolecules. Indeed, while 1 H and 13 C spectra are often included in the Supporting Information of a manuscript, they generally serve as an additional tool to confirm the molecular structure of a synthetic macromolecule, and only a few reports have demonstrated (blind) sequencing by solely making use of NMR spectroscopy. , The recent report from Kim and colleagues, in which they demonstrated the effective decoding of molecular information using 13 C NMR spectroscopy, together with the numerous studies on biomacromolecules, clearly confirm the sequencing potential of NMR. The main drawback, especially for longer macromolecules, is that larger product quantities are required in order to generate easily detectable signal-to-noise ratios.…”

Precision Sequence‐Defined Polymers: From Sequencing to Biological Functions

“…Kim and co‐workers sequenced the oligoester using 13 C NMR spectroscopy (Figure 4b). [33] In their work, the sequences of all the tetramers could be clearly identified by 13 C NMR analysis of the α‐C environment. While these examples illustrated the capabilities of NMR sequencing, it is important to acknowledge the limitations associated with this strategy in term of structural diversity and complexity.…”

Precision Sequence‐Defined Polymers: From Sequencing to Biological Functions

“…Reproduced with permission. [33] Copyright 2022, American Chemical Society. (c) Pulse-fuelled reading of molecular tape 1 (encoded À 1,0, + 1) using CD spectra.…”

“…(b) Decoding of oligoester (Si‐LLGGLLLL‐All) based on the 13 C NMR spectrum. Reproduced with permission [33] . Copyright 2022, American Chemical Society.…”