Applying NMR to structure determination

High-resolution nuclear magnetic resonance is an exceptional tool for determining the structure of a natural or synthetic molecule. Thanks to the diversity of parameters that can be measured, it can tackle all the problems posed by the examination of a molecule in solution. The originality of NMR compared with other spectroscopic techniques lies in the fact that it provides precise, individual information on the vast majority of the atoms making up a molecule, making it possible to identify the connections between atoms of different entities, skeletons and functional groups, and finally to situate them in space in relation to one another. This document focuses on medium-sized organic and bio-organic molecules.

The presentation of various examples will aim to show how to exploit the fundamental parameters of NMR and how to choose the different types of 1D NMR and 2D NMR experiments to establish a structure. A general strategy (using the simplest 1D and 2D NMR techniques) is presented, based on the study of three molecules, followed by an analysis of the problems posed by more complex structures (connections difficult to establish; tautomerism; presence of heteroatoms; exchange; distinction between diastereoisomers). Emphasis is placed on the choice of complementary experiments likely to provide a solution to each of these problems. The study of bio-organic molecules in the final section illustrates the need, in some cases, to use numerous experiments interactively.

Finally, it's important to point out that increasingly sophisticated NMR techniques are being developed all the time. Combined with the ever more remarkable performance of NMR equipment, these techniques bring gains in sensitivity, time savings and new solutions to the most difficult cases.