By Roberto Gil
The Nuclear Overhauser effect (NOE) is a very important tool in Nuclear Magnetic Resonance (NMR) for 3D structural analysis of small organic molecules. In this sense, the quantitative application of NOE is conventionally based on known reference distances that must be separated spectrally and are not always available. In this presentation, a new 3D structure evaluation and selection method will be described that does not require a reference distance, but uses structures optimized by Molecular Mechanics, allowing NOE evaluation even in molecules without suitable reference groups. A new approach to recover the structural information from faster NOESY experiments with shorter recycling delays (semi quantitative conditions) will be presented.[1]
In addition, this is complemented by a new method based on the use unsigned long-range proton-carbon coupling constants that allow the determination of the correct relative configuration from the molecular constitution. For this, 2JCH and 3JCH values collected from a single HSQMBC experiment. The study is mainly based on the comparison of 2,3JCH values calculated by DFT with the experimental once. The structural value of the 2JCH coupling constants was historically overlooked because of the lack semi-empirical equations such as those existing for 3-bond J coupling constants based on the Karplus relationship. The use DFT calculations revealed an impressive degree of structural discrimination when using only 2JCH coupling constants. The robustness of the method will be demonstrated using different small molecules of importance in organic chemistry as proof of concept. The combination of both methodologies positions them as a viable option for application in different fields of research such as organic, peptide and carbohydrate synthesis, identification and analysis of natural products, as well as in medicinal chemistry.[2]
References
1. Reference-free NOE NMR analysis. Koos, M.R.M.; Schulz, K.H.G.; Gil, R.R. Chem. Sci. 2020, 11(36), 9930-9936.
2. Computer-Assisted 3D Structure Elucidation (CASE-3D): The Structural Value of 2JCH in Addition to 3JCH Coupling Constants. Koos, M.R.M.; Navarro-Vazquez, A.; Anklin, C.; Gil, R.R. Angew. Chem. Int. Ed. 2020, 59(10), 3938-3941.