Computation of through-space F-19-F-19 scalar couplings via density functional theory

By using density functional theory it is demonstrated that the long-range F -19-F-19 J-couplings ((>3)J) seen in small organic molecules can be calcula ted with good accuracy using small molecule fragments and in some cases com plete molecules. The results reproduce the exponential distance dependence of J seen experimentally, demonstrate the dominance of the Fermi contact in teraction, and rule out any significant covalent or through-bond contributi ons to J in these systems. The calculations also verify an experimentally o bserved F-19-F-19 J-coupling seen between two [6-F]Trp residues in the prot ein dihydrofolate reductase (for d = 2.98 Angstrom), where there is clearly no covalent bonding between the two F-19 sites. The results also clarify t he abnormally small J-couplings seen previously in phenanthrenes and cycloh exenes, which are shown by nb initio and molecular mechanics geometry optim izations to be due to conversion of the supposedly planar structures to mor e distorted but less sterically hindered structures. These distortions incr ease the F-F distance and thereby reduce J(FF) The lack of any appreciable covalent bonding between the F-19 atoms in both the protein and the model s ystems, but the presence of significant J-couplings, emphasizes that all th at is required is Fermi contact, and the close spatial proximity of atoms. This result is of considerable current interest in the context of (long ran ge/through-space) hydrogen bond J-couplings in macromolecules.