Biopolymers such as DNA store information in their chains using controlled sequences of monomers. Here we describe a non-natural information-containing macromolecule that can store and retrieve digital information. Monodisperse sequence-encoded poly(alkoxyamine amide)s were synthesized using an iterative strategy employing two chemoselective steps: the reaction of a primary amine with an acid anhydride and the radical coupling of a carbon-centred radical with a nitroxide. A binary code was implemented in the polymer chains using three monomers: one nitroxide spacer and two interchangeable anhydrides defined as 0-bit and 1-bit. This methodology allows encryption of any desired sequence in the chains. Moreover, the formed sequences are easy to decode using tandem mass spectrometry. Indeed, these polymers follow predictable fragmentation pathways that can be easily deciphered. Moreover, poly(alkoxyamine amide)s are thermolabile. Thus, the digital information encrypted in the chains can be erased by heating the polymers in the solid state or in solution.

We report the intramolecular double compaction of sequence-controlled linear macromolecules into "structured" random coils. These compartmentalized single-chain objects were prepared by performing successive cross-linking reactions in an orthogonal fashion. The foldable precursors were synthesized by sequence-controlled copolymerization of styrene with N-substituted maleimides (MIs), namely pentafluorophenyl 4-maleimidobenzoate (1) and TIPS-protected N-propargyl maleimide (2). These two functional MIs allow intramolecular cross-linking. The activated ester pentafluorophenyl moieties of 1 were reacted with ethylenediamine, whereas the deprotected alkyne functions of 2 were self-reacted by Eglinton coupling. The compaction of model copolymers containing only one cross-linkable zone (i.e., either 1 or 2) was first studied. (1)H NMR and SEC analysis indicated that these structures could be efficiently compacted into single-chain objects. Thus, more complex copolymers containing two individually addressable cross-linking zones were prepared and sequentially compacted. Detailed characterization of the folding process indicated that double-compaction occurred and that the formed single-chain particles contain distinct cross-linked subdomains.

International audienceMonodisperse sequence-coded oligo(alkoxyamine amide)s were thoroughly investigated by tandem mass spectrometry to evaluate the robustness of this analytical approach as a reliable sequencing methodology. Studied samples were synthesized by orthogonal iterative chemistry on a solid support, and the 0/1 coding system was based on the mass of two amide synthons that alternate with a nitroxide moiety. The major fragmentation pathway experienced by these co-oligomers proceeded via homolysis of all fragile C-ON bonds between a coding unit and a nitroxide moiety. The relative rate of competing C-ON bond cleavages was observed to be sequence-dependent, offering an additional means to validate the sequences reconstructed from the MS/MS fragments. The same fragmentation rules applied for all studied samples, varying in terms of chain length, charge state, encoded sequence, end-groups, and nitroxide moiety. Ion mobility separation was coupled to MS/MS to sequence some more complex co-oligomers composed of both different nitroxides and coding units