High-resolution pure shift NMR spectroscopy for fast structural analysis of complex drug compounds with overlapping multiplets

Nuclear magnetic resonance (NMR) technology has played a critical role in the structural characterization and signal assignments of complex drugs and natural product samples for numerous years. Despite this, data analysis remains a challenging task due to the extensive signal overlaps and homonuclear J H-H coupling multiplets present in the conventional 1 H NMR spectra. Consequently, it is necessary to introduce a general and simple strategy to achieve structural determination of complex drugs. In this study, 1D pure shift NMR spectroscopy, an effective analysis tool, is applied to analyze four complex drug compounds, including two anti-inflammatory molecules (dexamethasone and icariin), and two antibiotic compounds (erythromycin and kanamycin sulfate). Compare to the conventional NMR methods, the pure shift NMR provided only chemical shift information in one-dimension, resulting in high-resolution and clean 1 H spectra with no multiplet structure by removing the effects of homonuclear coupling. The fast assignment of the complex proton resonances in drug molecules was achieved utilizing the decoupled spectra of 1D pure shift NMR, and the short acquisition time of selective decoupling pure shift (rt-BS) NMR. The conventional proton spectra were significantly simplified through pure shift NMR, which enabled us to adequately resolve the signal overlaps and distinguish the adjacent protons. The results show that the high-resolution PSYCHE and rt-BS NMR technique have great potential for the rapid analysis and total assignments of complex compounds suffering from severe scalar coupling in a wide variety of systems.