The importance of suppressing spin diffusion effects in the accurate determination of the spatial structure of a flexible molecule by nuclear Overhauser effect spectroscopy

• QUIET-NOESY method gives reliable and consistent effective atom–atom distances.
• Mentioned approach is recommended to use in molecules with possible spin diffusion.
• Extended distances set allowed calculating conformer fractions of ibuprofen in CDCl3.

Two-dimensional nuclear Overhauser effect spectroscopy is applied to the elucidation of conformation distribution of small molecules in solution. An essential influence of the nonlinear multistep magnetization transfer (spin diffusion) on the NMR-based analysis of conformers distribution for small druglike molecules in solution was revealed. Therefore, the spin diffusion should be eliminated from the obtained NMR data in order to obtain accurate results. Efficiency of QUIET-NOESY spectroscopy in solving the problem of accurate determination of inter-proton distances in a small molecule was shown in a study of ibuprofen. Although it requires much experimental time, this technique was found to be helpful to solve the spin diffusion problem.

Figure optionsDownload as PowerPoint slide