The Nuclear Magnetic Resonance (NMR) technique of secondary isotope multiplets of partially labeled entities (SIMPLE) enables identification and categorization of solution conformation intramolecular hydrogen bonds in a more accessible and efficient manner than other techniques. Developed and previously only tested on engineered small molecules, this method analyzes the deuterium equilibrium isotope effect (EIE), the peak shift resulting from the monodeuterated isotopologue of spatially proximate OH/OH groups, to determine the effects of solvent conditions and steric interactions on the H-bond. Both the direction of the shift and magnitude of the peak relative to the parent OH/OH peak over the course of titration with an exchangeable deuterium source can give information about the strength and geometry of the hydrogen bond. Here, this technique is applied to complex, bulky natural compounds with OH/OH geometries similar to previous simple molecule studies including anistatin (syn 2,4 diol), ginkgolide Β (1,4 cage diol), and rifampicin (1,8 aromatic). Molecules are titrated with deuterated methanol to characterize intramolecular H-bonding, and the results are compared with engineered small molecules and computational studies.

Characterizing natural molecule intramolecular bonding using NMR equilibrium isotope effect

2019 Spring National Meeting

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