Folding and duplex formation in mixed sequence recognition-encodedm-phenylene ethynylene polymers

Abstract

Oligomers equipped with complementary recognition units have the potential to encode and express chemical information in the same way as nucleic acids. The supramolecular assembly properties ofm-phenylene ethynylene polymers equipped with H-bond donor (D= phenol) and H-bond acceptor (A= phosphine oxide) side chains have been investigated in chloroform solution. Polymerisation of a bifunctional monomer in the presence of a monofunctional chain stopper was used for the one pot synthesis of families ofm-phenylene ethynylene polymers with sequencesADnAorDAnD(n= 1-5), which were separated by chromatography. All of the oligomers self-associate due to intermolecular H-bonding interactions, but intramolecular folding of the monomeric single strands can be studied in dilute solution. NMR and fluorescence spectroscopy show that the 3-mersADAandDADdo not fold, but there are intramolecular H-bonding interactions for all of the longer sequences. Nevertheless, 1 : 1 mixtures of sequence complementary oligomers all form stable duplexes. Duplex stability was quantified using DMSO denaturation experiments, which show that the association constant for duplex formation increases by an order of magnitude for every base-pairing interaction added to the chain, from 103M−1forADA·DADto 105M−1forADDDA·DAAAD. Intramolecular folding is the major pathway that competes with duplex formation between recognition-encoded oligomers and limits the fidelity of sequence-selective assembly. The experimental approach described here provides a practical strategy for rapid evaluation of suitability for the development of programmable synthetic polymers.