Residual Dipolar Couplings in Small-Molecule NMR

Abstract

The 2-D structure of most small molecules can be in principle straightforwardly determined by manual or automatic analysis of a set of experimental data that include the molecular formula, a series of 1-D and 2-D NMR experiments providing through-bond connectivity Correlation Spectroscopy (COSY), Total Correlations Spectroscopy (TOCSY), Heteronuclear Single-Quantum Correlation (HSQC), Heteronuclear Multiple-Bond Correlation (HMBC), and ADEQUATE/INADEQUATE-based experiments), and chemical shift predictions. Once the 2-D structure is available, the determination of relative configuration is a challenging task that it is commonly addressed in NMR by using nuclear Overhauser effect (NOE) and 3J coupling constant analysis. The development of the application of residual dipolar couplings (RDCs) to the configurational and conformational analysis of small molecules has matured enough in recent years to perform this task in an almost straightforward way, without even the need of using NOE and 3J coupling analysis, as will be presented here for the analysis of rigid and semirigid small molecules. Different types of alignment media, experiments to measure RDCs, and how the RDC data are used in the structural analysis of small molecules are described in this article.