Combined application of 2D NMR correlation methods and ab initio chemical shift calculations to the structure determination of new heterocyclic compounds

Blinov²,

Williams³

2009

During the process of molecular structure elucidation the selection of the most probable structural hypothesis may be based on chemical shift prediction. The prediction is carried out using either empirical or quantum-mechanical (QM) methods. When QM methods are used, NMR prediction commonly utilizes the GIAO option of the DFT approximation. In this approach the structural hypotheses are expected to be investigated by scientist. In this article we hope to show that the most rational manner by which to create structural hypotheses is actually by the application of an expert system capable of deducing all potential structures consistent with the experimental spectral data and specifically using 2D NMR data. When an expert system is used the best structure(s) can be distinguished using chemical shift prediction, which is best performed either by an incremental or neural net algorithm. The time-consuming QM calculations can then be applied, if necessary, to one or more of the 'best' structures to confirm the suggested solution.

Section: Examplementioning

confidence: 76%

Section: Examplementioning

confidence: 99%

Section: Examplementioning

confidence: 99%

Section: Examplementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A systematic approach for the generation and verification of structural hypotheses

Blinov²,

Williams³

2009

The application of empirical methods of ¹³C NMR chemical shift prediction as a filter for determining possible relative stereochemistry

Blinov²,

Williams³

2009

The reliable determination of stereocenters contained within chemical structures usually requires utilization of NMR data, chemical derivatization, molecular modeling, quantum-mechanical (QM) calculations and, if available, X-ray analysis. In this article, we show that the number of stereoisomers which need to be thoroughly verified, can be significantly reduced by the application of NMR chemical shift calculation to the full stereoisomer set of possibilities using a fragmental approach based on HOSE codes. The applicability of this suggested method is illustrated using experimental data published for a series of complex chemical structures.

Empirical and DFT GIAO quantum‐mechanical methods of ¹³C chemical shifts prediction: competitors or collaborators?

Blinov²,

Smurnyy³

et al. 2010

The accuracy of (13)C chemical shift prediction by both DFT GIAO quantum-mechanical (QM) and empirical methods was compared using 205 structures for which experimental and QM-calculated chemical shifts were published in the literature. For these structures, (13)C chemical shifts were calculated using HOSE code and neural network (NN) algorithms developed within our laboratory. In total, 2531 chemical shifts were analyzed and statistically processed. It has been shown that, in general, QM methods are capable of providing similar but inferior accuracy to the empirical approaches, but quite frequently they give larger mean average error values. For the structural set examined in this work, the following mean absolute errors (MAEs) were found: MAE(HOSE) = 1.58 ppm, MAE(NN) = 1.91 ppm and MAE(QM) = 3.29 ppm. A strategy of combined application of both the empirical and DFT GIAO approaches is suggested. The strategy could provide a synergistic effect if the advantages intrinsic to each method are exploited.