Multinuclear magnetic resonance studies of monomers and diemrs containing 2′‐fluoro‐2′‐deoxyadenosine

<jats:title>Abstract</jats:title><jats:p>A series of 2′‐fluorinated adenosine compounds, dAfl, dAflp, pdAfl, dAfl‐A, A‐dAfl, and dAfl‐dAfl, have been investigated by nmr spectroscopies. The <jats:sup>1</jats:sup>H‐, <jats:sup>19</jats:sup>F‐, and <jats:sup>31</jats:sup>P‐nmr data provide structural information from different parts of these moleucles. The p<jats:italic>K</jats:italic><jats:sub>a</jats:sub> of the phosphate group of these two 2′‐fluoro‐2′‐deoxyadenosine monophosphates was found to be the same as that of hte parent adenosine monophosphate. As for the pentose conformation, the <jats:sup>3</jats:sup><jats:italic>E</jats:italic> population is greatly increased as a result of the fluorine substitution at the C<jats:sub>2′</jats:sub> position. However, the populations of conformers of <jats:italic>gg</jats:italic> (C<jats:sub>4′</jats:sub>‐C<jats:sub>5′</jats:sub>) and <jats:italic>g′g</jats:italic>′ (C<jats:sub>5′</jats:sub>‐O<jats:sub>5′</jats:sub>) and the average angle ϕ′(C<jats:sub>3′</jats:sub>‐O<jats:sub>3′</jats:sub>) of the 2′‐fluoro compounds remain unchanged as compared to the natural riboadenosine monomer and dimer (A‐A). Thefefore, the backbone conformation of the 2′‐fluoro‐2′‐deoxy‐adenosine, its monophosphates and dimers, resembles that of RNA. The extent of base‐base overlapping in these 2′‐fluoro‐2′‐deoxy‐adenosine‐containing dimers is also found to be similar to or even greater than A‐A. Thus, the conformations of these compounds can be considered as those in the RNA family.</jats:p><jats:p>These fluorocompounds also serve as models for a careful study on the <jats:sup>19</jats:sup>F‐nmr in nucleic acid. The <jats:sup>19</jats:sup>F chemical‐shift values are sensitive to the environment of the fluorine atom such as ionic structure of the neighboring group(s) (phosphate of base), solvation, and ring‐ruccent anisotropic effect from the base(s). Qualitatively, the change of the <jats:sup>19</jats:sup>F chemical‐shift values (up to 2 ppm) is much larger than that of <jats:sup>1</jats:sup>H‐nmr (up to 0.5 ppm) in the dimers. Using dAfl·poly(U), poly(dAfl)·poly(dAfl), and poly(dAfl)·poly(U) helix–coil transition as model systems, the linewidth of <jats:sup>19</jats:sup>F in dAfl‐ residues reflects effectively the mobility of the unit in the nucleic acid complex as calibrated by uv data and by <jats:sup>1</jats:sup>H‐nmr. Therefore, application of <jats:sup>19</jats:sup>F‐nmr spectroscopy on fluorine‐substituted nucleic acid can also be used to detect nucleic acid‐nucleic acid interaction in complicated systems.</jats:p>