1. Development of a 13C NMR Chemical Shift Prediction Procedure Using B3LYP/cc-pVDZ and Empirically Derived Systematic Error Correction Terms: A Computational Small Molecule Structure Elucidation Method
- Author
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Klaus Wagner, Reginaldo A. Saraceno, Dongyue Xin, Christofer S. Tautermann, Keith Horspool, Zheng Yang, Om Chaudhary, Nina C. Gonnella, Keith R. Fandrick, C. Avery Sader, Paul-James Jones, Gordon Hansen, Chris H. Senanayake, and Carl A. Busacca
- Subjects
Basis (linear algebra) ,010405 organic chemistry ,Chemistry ,Chemical shift ,Organic Chemistry ,Carbon-13 NMR ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Data set ,Computational chemistry ,Linear regression ,Density functional theory ,Statistical physics ,Invariant (mathematics) ,Scaling - Abstract
An accurate and efficient procedure was developed for performing 13C NMR chemical shift calculations employing density functional theory with the gauge invariant atomic orbitals (DFT-GIAO). Benchmarking analysis was carried out, incorporating several density functionals and basis sets commonly used for prediction of 13C NMR chemical shifts, from which the B3LYP/cc-pVDZ level of theory was found to provide accurate results at low computational cost. Statistical analyses from a large data set of 13C NMR chemical shifts in DMSO are presented with TMS as the calculated reference and with empirical scaling parameters obtained from a linear regression analysis. Systematic errors were observed locally for key functional groups and carbon types, and correction factors were determined. The application of this process and associated correction factors enabled assignment of the correct structures of therapeutically relevant compounds in cases where experimental data yielded inconclusive or ambiguous results. Overall...
- Published
- 2017
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