Exploring the utility of computed chemical shifts in differentiating between diastereomers

Mercado, Calvin

Honours

2022

Cartmell, Chris
Pearson, Jason

Bachelor of Science

Faculty of Science. Honours in Chemistry

Chemistry

Chemistry

University of Prince Edward Island

Charlottetown, PE

Historically, computed chemical shifts have been used to aid with structural elucidation of novel compounds, and in some cases, to assist with the re-assignment of spectra of known but highly disputed molecules. Computed chemical shifts can be obtained from an NMR single-point calculation and is readily accessible from many software packages. Isotropic values will have to be parsed from the output of this calculation, which can then be subsequently converted to chemical shifts. The most common Show moreHistorically, computed chemical shifts have been used to aid with structural elucidation of novel compounds, and in some cases, to assist with the re-assignment of spectra of known but highly disputed molecules. Computed chemical shifts can be obtained from an NMR single-point calculation and is readily accessible from many software packages. Isotropic values will have to be parsed from the output of this calculation, which can then be subsequently converted to chemical shifts. The most common way to utilize computed chemical shift is to simply compare it to known experimental values. However, in cases where multiple isomers exists, this can be a daunting task. In this project, we outlined an attempt to utilize computed chemical shift in determining the correct configuration of a novel natural product. We observed a huge mismatch in the reported RMSE of computed chemical shift by at most a factor of 8 for 1H shifts and a factor of 4 for 13C shifts. We noted importantly the striking difference in the atom count between the benchmarked molecules and the molecule of interest, which prompted us to design a simple test to confirm the nature of the error. The results from this test strongly suggested that it was indeed the atom count that caused the discrepancy in the RMSE values, which also confirmed the computational nature of the error. Further testing also suggested that there are underlying physical aspects contributing to the error. While the results from these series of tests require more rigorous statistical work, it serves as a good preliminary data to aid with the engineering of more robust theoretical frameworks capable of producing sufficiently useful computed chemical shift values. Show less

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