The H(2)(18)O solvent-induced isotope shift in (19)F NMR

The H(2)(16)O/H(2)(18)O solvent-induced isotope shifts ((18)O SIIS) of the (19)F NMR signals of a number of fluorine compounds have been measured. These isotope shifts are observed to be upfield, downfield, or zero, depending on the specific compound and the precise solution conditions. At 25 degrees C and with an (18)O enrichment of 86%, the (18)O SIIS of several fluorinated amino acids were in the range of 0.0014-0.0018 ppm downfield. 5-Fluorouridine displays a significantly wider range of (18)O SIIS values. A 5-fluorouridine-labeled 16-mer RNA also displayed observable (18)O SIIS values, but the characteristics of these were significantly modified from those of free 5-fluorouridine. The experimental observations are consistent with the (18)O SIIS being composed of upfield and downfield components, with the relative contributions of these determining the size and direction of the overall isotope shift. This is discussed in terms of a combination of van der Waals interactions between the fluorine atom and the solvent, electrical and hydrogen bonding effects, and the perturbations to these due to (18)O substitution in the solvent water. This isotope effect promises to be a highly useful tool in a range of (19)F NMR studies.