An NMR strategy for obtaining multiple conformational constraints for 15N–13C spin-pair labelled organic solids

Abstract

This work demonstrates a solid-state NMR strategy for extracting multiple interatomic distance and angle constraints from moderately complex solid organic compounds containing a single ¹³C label and a single ¹⁵N label. It is shown that the constraints obtained for the compound cimetidine, with the labels placed at positions directed by the standard synthetic route, are sufficient to provide reliable estimates of 5 of the 8 torsional degrees of freedom in the molecule and are consistent with a molecular conformation close to that determined by crystallography. This strategy will be useful for determining the conformations of sparsely-labelled small molecules in motionally restrained environments, such as within the binding sites of membrane-embedded receptors.