Fluorinated nucleic acid constituents: a carbon-13 NMR study of adenosine, cytidine, uridine, and their fluorinated analogs

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Abstract
Adenosine, cytidine, uridine and their fluorinated analogs 2-fluoroadenosine, 5-fluorocytidine and 5-fluorouridine [antineoplastic drugs] were analyzed by 13C NMR spectroscopy. All carbon resonances of the sugar and base moieties are assigned. The C-F coupling constants of the base and the C-proton coupling constants between C of the base, protons of the base and the anomeric proton of the sugar were assigned. Effects of the F atom on carbon chemical shifts of the nucleoside are expressed as .DELTA..delta.F values [.DELTA..delta.F = .delta.(fluorinated nucleoside)-.delta.(normal nucleoside)]. Theoretical charge density calculations (CNDO/2) of the fluorinated and nonfluorinated base C are compared [.DELTA.ET = E(fluorinated nucleoside)-E(normal nucleoside)]. The .DELTA..delta.F and .DELTA.ET values correlate very well, except where a N atom is situated .beta. to the F atom. This apparent deviation is attributed to a lone-pair electron (LPE) effect of the N. Contributions of the LPE effect appear to vary 1JC,H and 1JC,F values in a predictable way. Long-range (4- and 5-bond) C-F coupling constants are observed in the base moiety. At these experimental conditions, introduction of the F atom has no measurable conformational effect on the sugar-base torsion angle.
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