Scalar coupling dihedral angle

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. 

Angular restraints are another important source of structural information. Several empirical relationships between scalar couplings and dihedral angles have been found during the last decades. The most important one is certainly the Karplus relation for -couplings. Another, relaxation-based angular restraint is the so-called CCR between two dipolar vectors or between a dipolar vector and a CSA tensor. 

Eq. (8.7), which provides the scalar coupling constant due to the interaction between nuclei, is analogous to Eq. (2.29), used to describe the dihedral angle dependence of the contact coupling constant due to the interaction between nuclei and electrons. 

NMR is the experimental tool of choice to explore conformational properties, especially of flexible small molecules in solution [55-57], Interpretation of NMR-derived structural parameters in combination with molecular modeling usually offers a view of the accessible conformations to ligands. The most relevant structural parameters derived from NMR are interproton distances obtained from NOE or ROE experiments, dihedral angle restraints from 3J scalar coupling measurements and, recently, residual dipolar couplings (RDCs) [58],... 

Figure 12.11. Illustration of the Karplus relationship between three-bond scalar coupling constants and the dihedral angle of the intervening bond. The relationship is indicated for the torsion angle of the H2 and H3 protons within the rigid core of taxol and related derivatives. See Fig. 12.6 for the structure of taxol.

Scalar coupling data can also yield valuable stereochemical information. The Karplus equation shown below provides a quantitative relationship between the three-bond scalar coupling constant J and the dihedral angle 4> between two protons. ... 

TROSY experiment for the measurement of three-bond scalar coupling constant between lH(i-l alpha) and 15N(i), which defines the dihedral angle." There are still relatively few examples of real applications where TROSY techniques have been essential to derive meaningful information. This is just a matter of time and this year has seen a few landmark illustrations. In a first... 

Extension of this type of analysis to scalar coupling Interactions Involving other nuclei requires establishment of the dihedral angle dependence of the vicinal couplings. Three approaches have been used (1) Measurement of coupling constants In conformatlonally constrained molecules (2) correlation of observed couplings with rotamer distributions In flexible molecules deduced previously on the basis of values (3)... 

H chemical shifts and scalar coupling constants can be measured directly from one-dimensional spectra if the peaks are well resolved, or, if spectra are too complex, they may be measured from DQF-COSY spectra crosspeaks. However, such measurements are often inaccurate and so are used as a basis of simulating the observed ID spectrum to obtain more accurate values. The measurements are used as a starting point and are systematically altered until the stimulated spectrum best matches the observed spectrum. H- H scalar coupling constants are especially useful in providing information on the dihedral angle within a HC-CH system and are thus one... 

Information on the structure of molecules can be obtained from nuclear pair interactions magnetic dipole-dipole interactions provide distance information, while scalar J couplings allow one to determine dihedral angles. 

Fig. 6.11. The dependence of the scalar coupling constants, J, of vicinal protons on the dihedral angle 4>.

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