Atomic Dipole Polarization in Predictions of Chemical Shifts of Amide and Pyrrolidine Protons

Abstract

A quantitative relationship has been established between the localization indices of electrons in atomic basins and chemical shifts of protons in amide and pyrrolidine fragments when they are present together in organic molecules. The fragments under consideration are important as key functional groups in the molecules of chiral inducers involved in stereoselective syntheses, in order to obtain drugs based on pyrimidinone heterocyclic systems. Integral properties of electron density, such as the magnitude of intra-atomic dipole polarization and charges of hydrogen atoms, calculated by integration of the electron density over the volumes of atomic basins, correlate with chemical shifts significantly better than the point atomic charges. Our proposed parametric model for the rapid prediction of chemical shifts is based on an equation that includes the electron localization index in the hydrogen atom basin as a factor. The developed approach offers a theoretical model for a rapid quantitative assessment of chemical shifts and makes it possible to formulate the main structural factors that provide correlation between the calculated and experimental chemical shifts of hydrogen atoms involved in intramolecular hydrogen bonds. It has been revealed that intramolecular hydrogen bonds are the main structural features that ensure the correlation of atomic integral characteristics with chemical shifts in the considered molecules. The results obtained in the course of theoretical modeling have been verified by comparison with the experimental 1H NMR data for 4-hydroxyproline-2-carboxanilide podands with different oxyethylene chain lengths, which are chiral inductors of stereoselective syntheses of drugs based on pyrimidinone heterocyclic systems.