Planta Med 2014; 80 - IL25
DOI: 10.1055/s-0034-1382316

Structural analysis of rigid and flexible small organic molecules assisted by residual dipolar couplings

RR Gil 1
  • 1Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213, USA

The 2D structure of most small molecules can be in principle straightforwardly determined by manual or automatic analysis of a set of experimental data that includes the molecular formula, a series of 1D and 2D NMR experiments providing trough-bond connectivity (COSY, TOCSY, HSQC, HMBC, HSQC-TOCSY and ADEQUATE/INADEQUATE based experiments), and chemical shift predictions. This is the main concept embedded in automatic structure elucidation programs. Once the 2D structure is available, the determination of its configuration and preferred conformation is a more challenging task. It is commonly addressed in NMR by using NOE and 3 J coupling constants analysis, as well as recent developments on the application of DFT calculation of 13C chemical shifts. However, it is difficult to assess how many samples are sitting on the laboratory's refrigerators waiting for an independent methodology that could lift some of the ambiguities generated by the use of conventional NMR methods. The development of the application of Residual Dipolar Couplings (RDCs) to the configurational and conformational analysis of small molecules has matured enough in the recent years to perform this task is an almost straightforward way, without even the need of using NOE and 3 J coupling analysis, as it will be presented here for the analysis of rigid and semi-rigid small molecules.