The Advantage of Automatic Peer-Reviewing of 13C-NMR Reference Data Using the CSEARCH-Protocol

Abstract

A systematic investigation of the experimental ¹³C-NMR spectra published in Molecules during the period of 1996 to 2015 with respect to their quality using CSEARCH-technology is described. It is shown that the systematic application of the CSEARCH-Robot-Referee during the peer-reviewing process prohibits at least the most trivial assignment errors and wrong structure proposals. In many cases, the correction of the assignments/chemical shift values is possible by manual inspection of the published tables; in certain cases, reprocessing of the original experimental data might help to clarify the situation, showing the urgent need for a public domain repository. A comparison of the significant key numbers derived for Molecules against those of other important journals in the field of natural product chemistry shows a quite similar level of quality for all publishers responsible for the six journals under investigation. From the results of this study, general rules for data handling, data storage, and manuscript preparation can be derived, helping to increase the quality of published NMR-data and making these data available as validated reference material.

Keywords: 13C-NMR; NMR; computer-assisted peer-reviewing; database; spectrum prediction; structure generation.

Figure 1

The structures of compound 5 (left) and compound 4 (right) from [33] together with the published ¹³C-NMR data (green, signal assigned by author, and yellow, signal exchangeable assigned) and the differences between experimental and predicted values (cred > 10 ppm, yellow < 10 ppm and >5 ppm, green < 5 ppm).

Figure 1

The structures of compound 5 (left) and compound 4 (right) from [33] together with the published ¹³C-NMR data (green, signal assigned by author, and yellow, signal exchangeable assigned) and the differences between experimental and predicted values (cred > 10 ppm, yellow < 10 ppm and >5 ppm, green < 5 ppm).

Figure 2

The structures of compound 4a (left), compound 4d (middle), and compound 4i (right) from [35], together with the published ¹³C-NMR data and the differences between the experimental and predicted values.

Figure 3

The ¹³C-NMR data of compound L1 as published in [36], together with the differences between the experimental and predicted values.

Figure 4

¹³C-NMR data of compounds 51, 26, 34, and 37 (columns from left to right) as published in [37], together with the published chemical shift values and the differences between the experimental and predicted chemical shift values.

Figure 5

¹³C-NMR data of compound 13 from [40] (left), compound 3 (mahanimbine) from [38] (middle), and compound 5 from [39] (right), together with the differences between the experimental and predicted chemical shift values. Differences larger than 99 ppm are always shown as 99 ppm.

Figure 5

¹³C-NMR data of compound 13 from [40] (left), compound 3 (mahanimbine) from [38] (middle), and compound 5 from [39] (right), together with the differences between the experimental and predicted chemical shift values. Differences larger than 99 ppm are always shown as 99 ppm.

Figure 6

¹³C-NMR data for compound 4 in [41] as published (left) and after correction (right), together with the differences between the experimental and predicted chemical shift values.

Figure 6

¹³C-NMR data for compound 4 in [41] as published (left) and after correction (right), together with the differences between the experimental and predicted chemical shift values.

Figure 7

¹³C-NMR data of compound 1 from [50] as published (left) and after correction (right), together with the differences between the experimental and predicted chemical shift values. The deviations remaining after the first step of correction (7.1/8.0 ppm) point out an additional assignment problem.

Figure 7

¹³C-NMR data of compound 1 from [50] as published (left) and after correction (right), together with the differences between the experimental and predicted chemical shift values. The deviations remaining after the first step of correction (7.1/8.0 ppm) point out an additional assignment problem.

Figure 8

Misassigned alkyl-chain of compound 11 from [51]. Experimental chemical shift values (middle) and differences between experimental and predicted chemical shift values (bottom).

Figure 9

Compound OH-1 from [52] as another example of a misassigned alkyl chain. Experimental chemical shift values (middle) and the differences between the experimental and predicted chemical shift values (bottom).

Figure 10

The data of compound 3 from [53] named pyrojacareubine, as published (left) and after correction of the structure (right), still holding additional assignment errors.

Figure 10

The data of compound 3 from [53] named pyrojacareubine, as published (left) and after correction of the structure (right), still holding additional assignment errors.

Figure 11

¹³C-NMR data of a benzophenone-derivate (already corrected with respect to the erroneously drawn hydroxy-group in position 2) taken from [55], as published (left) and the corrected version (right).

Figure 11

¹³C-NMR data of a benzophenone-derivate (already corrected with respect to the erroneously drawn hydroxy-group in position 2) taken from [55], as published (left) and the corrected version (right).

Figure 12

3ß-Hydroxy-17-acetamidoandrost-4-en-6-one as published in [56] for compound 8 (left), together with the differences between the experimental and predicted chemical shift values. The automatic structure revision proposes the 6-hydroxy-3-one derivative (right) leading to a much better, but not perfect coincidence, with the experimental data.

Figure 12

3ß-Hydroxy-17-acetamidoandrost-4-en-6-one as published in [56] for compound 8 (left), together with the differences between the experimental and predicted chemical shift values. The automatic structure revision proposes the 6-hydroxy-3-one derivative (right) leading to a much better, but not perfect coincidence, with the experimental data.

Figure 13

(left): Published structure of Moracin M (compound 7 in [41]) together with the given ¹³C-NMR data and the deviations between the experiment and prediction. (right): Fully automatic structure revision leading to excellent coincidence between the experimental and predicted chemical shift values.

Figure 13

(left): Published structure of Moracin M (compound 7 in [41]) together with the given ¹³C-NMR data and the deviations between the experiment and prediction. (right): Fully automatic structure revision leading to excellent coincidence between the experimental and predicted chemical shift values.