Nitrogen containing heterocyclic drugs that regulate the JAK-STAT pathway have proven therapeutic usage for a variety of disorders from hematological cancers to rheumatoid arthritis. The synthesis of these drugs to selectively inhibit specific JAK-STAT has become an active area of research for pharmaceutical companies. Nitrogen heterocycles are commonly hydrogen deficient, presenting challenges for their characterization. The method of choice to determine the structure of these novel drugs is Heteronuclear Multiple Bond Correlation (HMBC) Nuclear Magnetic Resonance (NMR) spectroscopy. The limitation of this method is that it requires prior knowledge of the molecular orbital electron density of the molecule to be characterized. The NMR spectrometer must be tuned to the resonance frequencies of scalar coupled atom pairs multiple bonds removed from one another in order for their coupling to be observed. The problem is that the trial and error approach to identifying the correct coupling constants requires a significant amount of very expensive spectrometer time. Here we describe the use of ab initio electron density calculations to predict the coupling constants such that the number of HMBC NMR experiments may be significantly reduced.
Malek, Petr, "Expediting Drug Discovery: Fast and Accurate Prediction of Coupling Constants for Nitrogen Heterocycles" (2014). College of Arts and Sciences Presentations. Paper 41.