Coupling constants dihedral angle

Interactive, online programs are available for the calculation of coupling constants, dihedral angles, and the H distance across thr a-linkages of some disaccharides, as well as a program for plotting up to five Karplus curves. 

J is almost always positive and its magnitude often exceeds that of T. It always depends in a predictable way on the dihedral angle ( ) between the outer two of the tluee bonds in die coupling patliway. Karplus first showed theoretically that T varies to a good approximation as A cos ( ) + B cos ( ), where A and B are constants, and also that A S>B [17]. Flis equation has received wide-ranging... 

Figure 1 The principal sources of structural data are the NOEs, which give information on the spatial proximity d of protons coupling constants, which give information on dihedral angles < i and residual dipolar couplings, which give information on the relative orientation 0 of a bond vector with respect to the molecule (to the magnetic anisotropy tensor or an alignment tensor). Protons are shown as spheres. The dashed line indicates a coordinate system rigidly attached to the molecule.

Figure 2.18. Vicinal HH coupling constants Jhh as a function of the dihedral angle 9 of the CH bonds concerned (Karplus-Conroy relationship)...

The //NMR spectrum (Fig. 2.19) displays anAB system for the protons adjacent to this bond the coupling constant = 72 Hz. From this can be deduced first that the dihedral angle 9 between the C7/bonds is about 180°, second that conformer 14b with minimised steric repulsion between the substituents predominates and third that there is restricted rotation around this CC bond. 

Vicinal CH coupling constants Hqh resemble vicinal HH coupling constants in the way that they depend on the cosine of the dihedral angle 9 between the CC bond to the coupled C atom and the C//bond to the coupled proton (cf Fig. 2.16), as illustrated by the Newman projections of the conformers 20a-c of a propane fragment. 

The coupling constant, J, between vicinal protons varies with dihedral angle, 0. The relationship between J and 0 is given by the Karplus equation . 

For each molecule (isomer A and isomer B), obtain dihedral angles for the following pairs of vicinal hydrogens Hg-Hy, H Hg, Hy-Hn, and Hg-Hyaxiai- Use the Karplus equation to estimate coupling constants for each pair, and then compare your predictions to the experimental coupling constants (see above). Which molecule is artemisin acetate and which is 6-epiartemisin acetate ... 

It is difficult to decide whether the discrepancy between the calculated and experimental data is due to a different conformational preference of the thietane dioxides in the liquid and the solid phase, or to the crude approximations included in the Karplus-Barfield equation. However, the relationship between vicinal coupling constants and dihedral angles appears qualitatively valid in thietane oxides and dioxides, particularly if trends instead of exact values are discussed . At any rate thietane dioxides, 1,3-dithietane dioxides and tetroxides maintain either planarity or a slightly distorted average vibrating conformation with a low barrier to ring planarity . 

Elucidation of the stereostructure - configuration and conformation - is the next step in structural analysis. Three main parameters are used to elucidate the stereochemistry. Scalar coupling constants (mainly vicinal couplings) provide informa-hon about dihedral bond angles within a structure. Another way to obtain this information is the use of cross-correlated relaxation (CCR), but this is rarely used for drug or drug-like molecules. 

Molecular mechanics (MM) calculations have been employed for determining dihedral angles and to establish a comparison with values calculated from coupling constants, during conformational studies of tricyclic and tetracyclic quinolizidine alkaloids. The MM results had to be treated with care, as they sometimes predicted ring conformations different to those supported by experimental data <1999JST215>. 

---