Efficient Protocol for the Synthesis of “N-Coded” Oligo- and Poly(N-Substituted Urethanes)

Abstract

Sequence-defined poly(N-substituted urethanes) were synthesized via a solid-phase iterative protocol including two successive orthogonal coupling steps: the formation of an activated carbonate and its chemoselective reaction with the secondary amine group of amino alcohol building blocks. This simple method was used to write binary information on the formed polymers using four-coded molecules, 2-(methylamino)ethanol, 2-(ethylamino)ethanol, 2-(propylamino)ethanol, and 2-(butylamino)ethanol, symbolizing binary dyads 00, 01, 10, and 11, respectively. The method is fast and allows synthesis of uniform oligomers and polymers with controlled lengths (4-mer to 28-mer) and digital information sequences. Furthermore, the coded poly(N-substituted urethanes) were easily characterized by electrospray mass spectrometry and decoded by tandem mass spectrometry. Overall, these digital macromolecules offer interesting advantages over conventional sequence-coded polyurethanes, i.e., synthesis of longer chains, reduced synthesis times, and better solubility and processing in common organic solvents.

Optimal conditions for tandem mass spectrometric sequencing of information‐containing nitrogen‐substituted polyurethanes

“…The sequence‐defined N‐substituted polyurethanes studied in this work (Table S1, supporting information) were synthesized using an iterative solid‐phase approach described in a recent publication 20 . All oligomer samples (a few mg) were first solubilized in methanol (SDS, Peypin, France), then diluted (1/10 3 to 1/10 4 , v/v) in a methanolic solution of ammonium acetate (3 mM) or sodium chloride (0.1 mM), both purchased from Sigma‐Aldrich (St Louis, MO, USA), prior to being subjected to ESI.…”

“…The same strategy is followed here to optimize the collision‐induced dissociation (CID) of poly(N‐substituted urethane)s, further named N–R Pus, to distinguish them from regular N–H PUs after the nomenclature proposed by Montaudo et al 18 Compared with N–H PUs with the alkyl coding moiety in the backbone (Scheme 1A), N–R PUs have their code implemented in the alkyl N‐substituent (Scheme 1B), which precludes hydrogen bonding between urethane units, hence preventing crystallization and solubility issues 19 . N–R PUs were prepared with amino alcohol building blocks containing secondary amine functions 20 and the use of four monomers holding R chains of different mass permits definition of a dyad‐based alphabet (Scheme 1B), hence also enhancing storage density. Another structural improvement of N–R PUs over N–H PUs is the methyl ϖ end‐group instead of OH, which avoids esterification of the COOH‐,OH‐terminated oligomers sometimes observed during chain release from the synthesis solid support 21 .…”

Damage and Repair in Informational Poly(N‐substituted urethane)s

“…In this case, chain unzipping was triggered by a terminal OH‐group and required basic conditions and elevated temperatures (70 °C, microwave) to proceed. In the present work, we investigated the depolymerization in basic medium of sequence‐coded poly( N ‐substituted urethane)s, a promising new family of digital polymers [7e] . As described in the following paragraphs, depolymerization occurs at room temperature and can be finely tuned by macromolecular design.…”

“…The poly( N ‐substituted urethane)s studied in this work were all synthesized using a recently‐reported orthogonal solid‐phase synthesis protocol [7e] . Figure 1 shows their general structure.…”

Desorption Electrospray Ionization (DESI) of Digital Polymers: Direct Tandem Mass Spectrometry Decoding and Imaging from Materials Surfaces

“…[ 9,10 ] Still, such chain‐lengths are far above the upper limit of 28 repeating units ever demonstrated for de novo sequencing of digitally encoded polymers by MS/MS. [ 11,12 ] Indeed, in order to assess monomer connectivity along the whole chain, the same dissociation reactions have to proceed at all repeating units: the number of fragments rapidly increases with the degree of polymerization (DP), leading to signal dilution which hampers detectability of sequencing fragments. To address this issue, the chemical structure of monomers can be optimized to decrease their MS/MS reactivity and hence lower the number of dissociation pathways per repeating unit.…”