Synthesis of Molecularly Encoded Oligomers Using a Chemoselective “AB + CD” Iterative Approach

Abstract

A library of eight sequence-defined model oligomers, whose sequence is based on a (0,1) binary code, is prepared through chemoselective repeating cycles of amidification and copper-assisted alkyne-azide cycloaddition reactions from a non-modified Wang resin. This library is constructed from two AB (A = acid, B = alkyne) building blocks, i.e., 4-pentynoic acid and 2-methyl-4-pentynoic acid acting, respectively, as non-coding (0) and coding (1) monomer, and 1-amino-11-azido-3,6,9-trioxaundecane as complementary CD (C = amine, D = azide) spacer building block. In particular, encoded triads are synthesized by consecutive covalent attachment of five building blocks (i.e., three coding/non-coding monomers and two spacers). In this communication, optimal protocols for the synthesis of the targeted oligomers are reported along with their full characterization by (1) H NMR, MALDI-TOF mass spectrometry, and size-exclusion chromatography. It is found that all possible encoded triads (i.e., eight possibilities) could be synthesized using this approach. Indeed, monodisperse sequence-defined oligomers are prepared and characterized in all cases.

Tandem mass spectrometry sequencing in the negative ion mode to read binary information encoded in sequence‐defined poly(alkoxyamine amide)s

“…Information‐containing polymers are a new promising class of synthetic macromolecules in which messages are encoded by a defined sequence of comonomers . Using two monomers intentionally defined as 0‐bit and 1‐bit, a string of binary information was recently implemented in synthetic polymers such as poly(triazole amide)s, polyphosphates and poly(alkoxyamine amide)s . In the latter case, the molecular structure of the studied poly(alkoxyamine amide)s contained two coded amide synthons, –NH–(CO)–CH(CH) 3 – (71.0 Da) and –NH–(CO)–C((CH) 3 ) 2 – (85.1 Da), respectively defined as the 0‐ and 1‐bit, spaced by a TEMPO (T) alkoxyamine moiety (Scheme ).…”

“…Information-containing polymers are a new promising class of synthetic macromolecules in which messages are encoded by a defined sequence of comonomers. [1][2][3] Using two monomers intentionally defined as 0-bit and 1-bit, a string of binary information was recently implemented in synthetic polymers such as poly(triazole amide)s, [4][5][6] polyphosphates [7] and poly(alkoxyamine amide)s. [8] In the latter case, the molecular structure of the studied poly(alkoxyamine amide)s contained two coded amide synthons, -NH-(CO)-CH(CH) 3 -(71.0 Da) and -NH-(CO)-C((CH) 3 ) 2 -(85.1 Da), respectively defined as the 0-and 1-bit, spaced by a TEMPO (T) alkoxyamine moiety (Scheme 1). These sequence-defined terpolymers were synthesized using iterative solid-phase methodologies based on either a monomer-by-monomer construction of the chains [8,9] or a convergent approach involving pre-prepared X-T-X dyads (with X = 0 or 1) to shorten the preparation time of long chains.…”

Recent developments in the synthesis of sequence controlled polymers

“…Lutz and coworkers [20,80] developed solid phase synthesis using modified Wang resin in combination with orthogonal coupling reactions such as azide alkyne cycloaddi-…”

“…In some cases, the term "sequence regulated polymer" was used in a similar way [14][15][16][17]. The nomenclature of "sequence defined" [18][19][20] or "sequence specific" [21,22] polymer emphasized particular order of monomer units which were connected periodically or aperiodically.…”

Cleavable Binary Dyads: Simplifying Data Extraction and Increasing Storage Density in Digital Polymers

“…Such polymers are information-containing macromolecules that contain ab inary message stored in their chains. [4] This first proof-of-concept was extremely rudimentary,s ince the oligo(triazole amide)s described in this communication contained only 3bits of information. [3] In order to write ad igital sequence in the polymers,t wo comonomers,defined as a0/1 binary alphabet, are used.…”