Configuration and conformation

The determination of the relative configuration of small molecules is a well established topic for NMR. A number of NMR parameters are sensitive to the relative positions of nuclei through space as well as the angles and dihedrals between the connecting bonds. Through accurate measurements of homonuclear and heteronuclear coupling constants, NOE buildup and residual dipolar couplings the relative configuration of a small molecule can in the majority of cases be determined. Recently, NMR has also been involved in the determination of absolute configuration, either directly by measuring RDCs in non-racemic gels (published success stories have been challenged, but robust protocols are coming, or so they say), or indirectly by validating structure ensembles for optical spectroscopy simulations. The pharmaceutical industry has also recently started to pay more attention to the three dimensional conformation distributions in solution of small flexible drugs candidates, something that NMR validated ensembles can describe.

Conformation by NMR

Configuration by NMR