We report a dynamic covalent self-assembly technique employing temperature mediated hybridization of peptoid oligomers bearing maleimide- and furan-based pendant groups to afford molecular ladders incorporating Diels–Alder adduct-based rungs. By changing the reaction temperature, this system enables the equilibrium state to be readily varied facilitating the error correction mechanism without altering reagent concentrations.<br/>To enable the number of Diels–Alder adduct rungs to be determined by mass spectrometry, a registry-dependent mass change was achieved by employing a base-catalyzed thiol-Michael addition reaction between any un-reacted maleimide pendant groups and a low molecular weight thiol.<br/>This approach revealed that, whereas hybridization of trifunctional maleimide- and furan-bearing oligomers did not exclusively yield the completely formed, in-registry molecular ladder within 24 hours, rearrangement towards the target, in-registry ladder product proceeded over extended reaction times.<br/>By employing a slow temperature ramp from high to low temperature, sequence-selective hybridization in a model mixture of sequence-specific tetra-functional peptoids was obtained, approximating the thermal cycle employed for nucleic acid hybridization.

Dynamic covalent assembly of peptoid-based ladder oligomers employing thermally reversible Diels–Alder cycloaddition

ACS Spring 2022

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