Computation of Through-Space ¹⁹F−¹⁹F Scalar Couplings via Density Functional Theory

Abstract

By using density functional theory it is demonstrated that the long-range 19F−19F J-couplings (>3J) seen in small organic molecules can be calculated with good accuracy using small molecule fragments and in some cases complete molecules. The results reproduce the exponential distance dependence of J seen experimentally, demonstrate the dominance of the Fermi contact interaction, and rule out any significant covalent or through-bond contributions to J in these systems. The calculations also verify an experimentally observed 19F−19F J-coupling seen between two [6-F]Trp residues in the protein dihydrofolate reductase (for d = 2.98 Å), where there is clearly no covalent bonding between the two 19F sites. The results also clarify the abnormally small J-couplings seen previously in phenanthrenes and cyclohexenes, which are shown by ab initio and molecular mechanics geometry optimizations to be due to conversion of the supposedly planar structures to more distorted but less sterically hindered structures. These distortions increase the F−F distance and thereby reduce JFF. The lack of any appreciable covalent bonding between the 19F atoms in both the protein and the model systems, but the presence of significant J-couplings, emphasizes that all that is required is Fermi contact, and the close spatial proximity of atoms. This result is of considerable current interest in the context of (long range/through-space) hydrogen bond J-couplings in macromolecules.