| Abstract: | A series of 2′-fluorinated adenosine compounds, dAfl, dAflp, pdAfl, dAfl-A, A-dAfl, and dAfl-dAfl, have been investigated by nmr spectroscopies. The 1H-, 19F-, and 31P-nmr data provide structural information from different parts of these moleucles. The pKa 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 3E population is greatly increased as a result of the fluorine substitution at the C2′ position. However, the populations of conformers of gg (C4′-C5′) and g′g′ (C5′-O5′) and the average angle ?′(C3′-O3′) 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. These fluorocompounds also serve as models for a careful study on the 19F-nmr in nucleic acid. The 19F 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 19F chemical-shift values (up to 2 ppm) is much larger than that of 1H-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 19F in dAfl- residues reflects effectively the mobility of the unit in the nucleic acid complex as calibrated by uv data and by 1H-nmr. Therefore, application of 19F-nmr spectroscopy on fluorine-substituted nucleic acid can also be used to detect nucleic acid-nucleic acid interaction in complicated systems. |
