The Effect of Molecular Conformation on the Accuracy of Theoretical 1H and 13C Chemical Shifts Calculated by Ab Initio Methods for Metabolic Mixture Analysis
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- 作者：Eisuke Chikayama ; Yudai Shimbo ; Keiko Komatsu ; Jun Kikuchi
- 刊名：Journal of Physical Chemistry B
- 出版年：2016
- 出版时间：April 14, 2016
- 年：2016
- 卷：120
- 期：14
- 页码：3479-3487
- 全文大小：664K
- 年卷期：0
- ISSN：1520-5207
文摘
NMR spectroscopy is a powerful method for analyzing metabolic mixtures. The information obtained from an NMR spectrum is in the form of physical parameters, such as chemical shifts, and construction of databases for many metabolites will be useful for data interpretation. To increase the accuracy of theoretical chemical shifts for development of a database for a variety of metabolites, the effects of sets of conformations (structural ensembles) and the levels of theory on computations of theoretical chemical shifts were systematically investigated for a set of 29 small molecules in the present study. For each of the 29 compounds, 101 structures were generated by classical molecular dynamics at 298.15 K, and then theoretical chemical shifts for 164 1H and 123 13C atoms were calculated by ab initio quantum chemical methods. Six levels of theory were used by pairing Hartree–Fock, B3LYP (density functional theory), or second order Møller–Plesset perturbation with 6-31G or aug-cc-pVDZ basis set. The six average fluctuations in the 1H chemical shift were ±0.63, ± 0.59, ± 0.70, ± 0.62, ± 0.75, and ±0.66 ppm for the structural ensembles, and the six average errors were ±0.34, ± 0.27, ± 0.32, ± 0.25, ± 0.32, and ±0.25 ppm. The results showed that chemical shift fluctuations with changes in the conformation because of molecular motion were larger than the differences between computed and experimental chemical shifts for all six levels of theory. In conclusion, selection of an appropriate structural ensemble should be performed before theoretical chemical shift calculations for development of an accurate database for a variety of metabolites.