Exploring Atypical Fluorine–Hydrogen Bonds and Their Effects on Nucleoside Conformations

Daniel O'Reilly, Robin S. Stein, Mihai Burai Patrascu, Sunit Kumar Jana, Jerry Kurian, Nicolas Moitessier, Masad J. Damha

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The ability of fluorine to serve as a hydrogen-bond acceptor has been debated for many years. Short fluorine–hydrogen contacts are thought to play a key role in stabilizing some complex supramolecular systems. To directly probe the existence of fluorine–hydrogen bonds, we have performed NMR spectroscopy and computational modeling on a series of C2′-fluorinated nucleosides. Specifically, quantum mechanics/molecular mechanics (QM/MM) analysis and [19F,1H] HMBC NMR experiments provided direct evidence for a C−H⋅⋅⋅F hydrogen bond in a 2′-F,4′-C-α-alkyl-ribonucleoside analogue. This interaction was also supported by QTAIM and NBO analyses, which confirmed a bond critical point for the C−H⋅⋅⋅F interaction (0.74 kcal mol−1). In contrast, although conformational analysis and NMR experiments of 2′-deoxy-2′-fluoro-arabinonucleosides indicated a close proximity between the 2′-fluorine and the H6/8 protons of the nucleobase, molecular simulations did not provide evidence for a C−H⋅⋅⋅F hydrogen bond.

Original languageEnglish (US)
Pages (from-to)16432-16439
Number of pages8
JournalChemistry - A European Journal
Volume24
Issue number61
DOIs
StatePublished - Nov 2 2018
Externally publishedYes

Keywords

  • conformational analysis
  • fluorine
  • hydrogen bonds
  • NMR spectroscopy
  • nucleosides

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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