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 language | English (US) |
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Pages (from-to) | 16432-16439 |
Number of pages | 8 |
Journal | Chemistry - A European Journal |
Volume | 24 |
Issue number | 61 |
DOIs | |
State | Published - Nov 2 2018 |
Externally published | Yes |
Keywords
- conformational analysis
- fluorine
- hydrogen bonds
- NMR spectroscopy
- nucleosides
ASJC Scopus subject areas
- Catalysis
- Organic Chemistry