Long, self-assembled molecular ladders by cooperative dynamic covalent reactions

Abstract

The self-assembly of long-sequence, peptoid-based molecular ladders with up to 16 rungs was demonstrated via the dimerization of oligomeric precursors bearing dynamic covalent pendant groups, with delineation of three potential mechanisms. These include a ‘molecular zipper’, whereby hybridization starts at one end followed by a series of imine condensation reactions to zip up complementary strands, or a ‘molecular hand-shake line’ or ‘toehold displacement’, whereby the molecular ladder formation would occur by shuffling or exchanging through bond rearrangement via cooperative transimination and imine metathesis reactions. MALDI mass spectrometry was used to determine the hybridization registry mechanism, with distance measurements using Förster resonance energy transfer (FRET) further confirming the registry mechanism, indicating that two complementary strands initially interact and bind by rapidly ‘zipping-up’ at any point generating molecular ladders with an arbitrary number of rungs, followed by slowly shuffling through a ‘molecular hand-shake line’ until these ladders come into registry.