Conformational preference in difluoroacetamide oligomers: probing the potential for foldamers with C–H⋯O hydrogen bonds

Matej Žabka, Jonathan Clayden*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

The C–H bond of a difluoroacetamide group, acidified by two adjacent fluorine atoms, could in principle provide conformational organisation for foldamers based on C–H⋯O hydrogen bonds. We find that in model oligomeric systems, this weak hydrogen bond leads only to partial organisation of the secondary structure, with the conformational preference of the difluoroacetamide groups being predominantly governed by dipole stabilisation. Hydrogen-bonded foldamers,1,2 and more recently polarity-coherent but conformationally flexible oligoureas based on ethylenediamine linkers 1 (Fig. 1A),3 have found widespread use in structural chemistry4 and catalysis,5,6 and as switchable devices,7 and have demonstrated potential biological applications.8 Hydrogen-bonded foldamer structures incorporate a range of structural motifs, but the most common are oligoamides and oligoureas or thioureas.9 These functional groups provide conformational control through strong N–H⋯O[double bond, length as m-dash]C hydrogen bonds, similar to those governing secondary structures in peptides.
Original languageEnglish
Pages (from-to)5939-5943
Number of pages5
JournalOrganic & biomolecular chemistry
Volume21
Issue number29
Early online date27 Jun 2023
DOIs
Publication statusE-pub ahead of print - 27 Jun 2023

Bibliographical note

Funding Information:
The work was supported by the ERC (AdG DOGMATRON, grant agreement 883786). This work used the Isambard 2 UK National Tier-2 HPC Service ( https://gw4.ac.uk/isambard/ ) operated by GW4 and the UK Met Office; and funded by EPSRC (EP/T022078/1). We acknowledge the use of the University of Bristol's NMR (Dr Chris Williams) and X-ray crystallography (Dr Hazel Sparkes and Dr Natalie Pridmore) facilities.

Publisher Copyright:
© 2023 The Royal Society of Chemistry.

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