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Through‐Space 7 J HF and 6 J CF Spin–Spin Couplings in 2′,3′‐Dideoxy‐4′‐fluoroalkylnucleosides. The Role of Sugar Ring Conformation and Solvent Effect
Author(s) -
Mele Andrea,
Salani Giuliana,
Viani Fiorenza,
Bravo Pierfrancesco
Publication year - 1997
Publication title -
magnetic resonance in chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0749-1581
DOI - 10.1002/(sici)1097-458x(199703)35:3<168::aid-omr58>3.0.co;2-2
Subject(s) - chemistry , intramolecular force , hydrogen bond , intermolecular force , ring (chemistry) , anomer , moiety , solvent , solvent effects , crystallography , proton nmr , nuclear overhauser effect , stereochemistry , computational chemistry , nuclear magnetic resonance spectroscopy , molecule , organic chemistry
1 H and 13 C NMR spectra of seven compounds of a new class of synthetic fluorinated nucleosides, 2′,3′‐dideoxy‐4′‐fluoroalkylthymidine and 2′,3′‐dideoxy‐4′‐fluoroalkylfluorouridine, showed long‐range 7 J HF and 6 J CF couplings between the F of the fluoroalkyl moiety and H‐6 (and C‐6) of the nucleobase. All the couplings were selectively detected on α anomers only, and 1 H{ 19 F} NOE difference spectra indicated that the F nucleus and H‐6 are also in spatial proximity, supporting the hypothesis of a through‐space mechanism for the transmission of the nuclear spin information. Molecular mechanics calculations on α‐2′,3′‐dideoxy‐4′‐fluoroalkylthymidine as a model compound indicated that F···H‐6 distance spans the range 2.58–2.73 Å irrespective of the sugar ring conformation and the F···H‐6—C‐6 angle is within the range 145–159°. Calculated data support the view of an attractive interaction between F and H‐6 of the base, consistent with an intramolecular hydrogen bond. Experimental evidence to this hypothesis are provided by NMR measurement in different solvents: the observed values of 7 J HF and 6 J CF decrease with increasing dielectric constant of the solvent and with the increasing capability of the solvent to establish intermolecular hydrogen bonds in competition with the intramolecular ones, i.e. passing from CDCl 3 to acetone‐ d 6 and to DMSO‐ d 6 . © 1997 by John Wiley & Sons, Ltd.