H-Bonded Duplexes based on a Phenylacetylene Backbone.

Jonathan A Swain,Christopher A Hunter,Giulia Iadevaia

doi:10.1021/jacs.8b08087

Jonathan A Swain, Christopher A Hunter + Show 1 more

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https://doi.org/10.1021/jacs.8b08087

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Abstract

Complementary phenylacetylene oligomers equipped with phenol and phosphine oxide recognition sites form stable multiply H-bonded duplexes in toluene solution. Oligomers were prepared by Sonogashira coupling of diiodobenzene and bis-acetylene building blocks in the presence of monoacetylene chain terminators. The product mixtures were separated by reverse phase preparative high-pressure liquid chromatography to give a series of pure oligomers up to seven recognition units in length. Duplex formation between length complementary homo-oligomers was demonstrated by 31P NMR denaturation experiments using dimethyl sulfoxide as a competing H-bond acceptor. The denaturation experiments were used to determine the association constants for duplex formation, which increase by nearly 2 orders of magnitude for every phenol-phosphine oxide base-pair added. These experiments show that the phenylacetylene backbone supports formation of extended duplexes with multiple cooperative intermolecular H-bonding interactions, and together with previous studies on the mixed sequence phenylacetylene 2-mer, suggest that this supramolecular architecture is a promising candidate for the development of synthetic information molecules that parallel the properties of nucleic acids.

Highlights

Nucleic acids encode information in the sequence of monomer units, and this structure provided the molecular basis for the evolution of biological life
We have shown that oligomers equipped with single H-bond recognition modules form stable duplexes in nonpolar solvents.12a−g It is possible to interchange different H-bond donor−acceptor recognition motifs (D·A) on the same backbone and maintain the duplex forming properties of the oligomers.12c Oligomers have been prepared using reductive amination chemistry and using thiol−ene coupling, and both types of backbone lead to the formation of stable duplexes
The average oligomer length can be controlled by adding monofunctional chain stoppers to the modules bearing two acetylene moieties were synthesized using the route shown in Scheme 1

Summary

■ INTRODUCTION

Nucleic acids encode information in the sequence of monomer units, and this structure provided the molecular basis for the evolution of biological life. The information is read through sequence-selective duplex formation and copied through template synthesis.[1] The sequence of monomer units defines the three-dimensional structures and functional properties of single-stranded nucleic acids.[2] Modified analogues of nucleic acids have been reported,[3] where the sugar,[4] the phosphate linker,[5] or the base pairing system[6] have been replaced and the ability of forming duplexes was not affected, suggesting that fully synthetic information molecules may be able to have some or all the functions of nucleic acids. When mixed donor−acceptor sequences were prepared, it became clear that the conformational properties of the backbone play a key role in discriminating between intramolecular H-bonding interactions that lead to folding and intermolecular interactions that lead to duplex formation. Architecture leads to the formation of very stable H-bonded duplexes in toluene

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ REFERENCES