Scalar Coupling Constants—Their Analysis and Their Application for the Elucidation of Structures

Abstract

Since their discovery in the early fifties, scalar/coupling constants have been of great interest to the NMR spectroscopist. Their impact on structure determination by NMR spectroscopy is founded on the fact that the size of the coupling constant is directly related to molecular conformation. Today, for most chemical substances the parameters for the Karplus relationship, which relates the vicinial (3‐bond) coupling constant to the dihedral angle, have been determined. In addition to proton–proton distances, the application of coupling constants in modern conformational analysis is indispensable. In the study of larger molecules which are of current interest, more and more involved experiments are necessary in order to overcome signal overlap and increasing line widths. A large number of experimental techniques for the determination of coupling constants has been developed; however, for this reason the choice of the most appropriate experiment to use has become more difficult. This decision must be made carefully to maximize instrument usage and obtain the largest number of couplings with the greatest accuracy possible. Many of the computer programs used in structure calculations can directly apply coupling constant restraints, similar to proton–proton distances developed from NOEs. Therefore, not only is the quality of the structure improved, but the molecular motions (internal dynamics) are better described. In this article, we review the techniques that exist today with particular attention paid to helping the non‐expert to choose the appropriate experiment for the problem at hand. In addition, the use of coupling constants in computer simulations are discussed.

Structural Features of Dinoflagellate Toxins Underlying Biological Activity as Viewed by NMR

“…Additional carbon-proton coupling 2;3 J C,H greatly expands the utility of the coupling constants. Due to progress in two-dimensional NMR techniques, 46 2;3 J C,H values in complicated natural products have become measurable. These conditions have led to the invention of a new method called ''Jbased configuration analysis'' for assigning the relative configuration of acyclic structures in natural products.…”

Recommendations for the presentation of NMR structures of proteins and nucleic acids

“…This includes the specific Karplus-type relationships employed, their representation by an energetic penalty function during the structure calculation (see, for example, [50]), and possibly additional criteria used to resolve the up to fourfold degeneracy of the Karplus relation between torsion angle and J-coupling.…”

Determining the Stereochemistry of Molecules from Residual Dipolar Couplings (RDCs)

“…A detailed description of methods originally developed for extraction of scalar couplings, which, in principle, can be used for studying compounds in anisotropic environment if dipolar contributions are small, can be found in the literature. 6 New developments deal with problems arising from larger distribution of magnitudes of T-values compared to respective J-values and are reviewed among other issues by, e.g., Luy 7,8 and Thiele. 9 Obviously, equation (4) is only applicable if signs of the corresponding observables are known.…”

“…equation (5)] and direction cosines of the axis of the fixed molecular frame to the internuclear vector leading to equation (6).…”