The development of an NMR chemical shift prediction application with the accuracy necessary to grade proton NMR spectra for identity

• Published in: Magnetic resonance in chemistry 2009-12, Vol.47 (12), p.1055-1061
• Main Authors: Spanton, Stephen G., Whittern, David
• Format: Article
• Language: English
• Subjects: 13C; Automated; chemical shift prediction; Drugs; Estimates; Grading; Magnetic resonance; Magnetic Resonance Spectroscopy - methods; Magnetic Resonance Spectroscopy - standards; NMR; Nuclear magnetic resonance; Permissible error; Protons; Reference Standards; Software; Spectra
• ISSN: 0749-1581; 1097-458X; 1097-458X
• DOI: 10.1002/mrc.2512

We have developed an NMR chemical shift prediction system that enables high throughput automatic grading of NMR spectra. In support of high throughput synthetic efforts for our drug discovery program, a rapid and accurate analysis for identity was needed. The system was designed and implemented to take advantage of the NMR assignments that had been tabulated on internally generated research compounds. The system has been operational for four years and has been used in conjunction with an internally written grading program to successfully analyze several hundred thousand samples based only on their 1D 1H spectrum. A focused test of the system's accuracy on 1006 molecules demonstrated the ability to estimate the proton chemical shift with an average error of +/−0.16 ppm. This level of chemical shift accuracy allows for reliable structure confirmation by automated analysis using only proton NMR. Copyright © 2009 John Wiley & Sons, Ltd. An NMR chemical shift prediction system was developed that enables high throughput automatic grading of NMR Spectra. This system used atom connectivity, stereochemistry, and experimental solvent. The accuracy of the system was demonstrated to estimate proton chemical shifts with an average error of +/−0.16 ppm.