Usage of Relative Differences of Experimental and Calculated Vicinal Constants 3JHH for Conformational Analysis of Rigid Molecules in Liquid

Abstract

Comparison of the relative differences between the experimental and calculated values of proton–proton vicinal scalar constants obtained from nuclear magnetic resonance spectra of two structurally similar organic molecules makes it possible to increase the efficiency of using Karplus relationship for experimental detection and quantitative description of the conformational distortions in molecules under investigation. Advantages and disadvantages of the proposed approach are considered on the examples of the study of two pairs of rigid steroid molecules in solution where they are in a single conformation. These steroids have potential biological activity which is determined by their structural and conformational features. There is only one structural difference in each pair of compared steroids. The influence of small modifications such as substituent variation on the molecules spatial structure was investigated by the joint use of molecular optimization methods (semi-empirical and molecular mechanic) to determine the dihedral angles and Karplus-type equation of C.A.G. Haasnoot, F.A.A.M. de Leeuw and C.A. Altona to calculate vicinal constants in ethane fragments. It was shown that the usage of relative differences of experimental and calculated vicinal constants for conformational analysis of rigid molecules eliminates systematic errors of vicinal constant calculations. Such approach allows us to detect small distortions between conformations of comparable molecules with high accuracy, which are concluded in the differences of the corresponding dihedral angles within not more than 10°–15°. The proposed approach is a more sensitive way of studying small specific features of the spatial structure of molecules in comparison with the known methods on the basis of Karplus-type equation in which the absolute values of experimental and calculated vicinal proton–proton constants are compared.