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Organic structure determination using atomic-resolution scanning probe microscopy

Abstract

Nature offers a huge and only partially explored variety of small molecules with potential pharmaceutical applications. Commonly used characterization methods for natural products include spectroscopic techniques such as nuclear magnetic resonance spectroscopy and mass spectrometry. In some cases, however, these techniques do not succeed in the unambiguous determination of the chemical structure of unknown compounds. To validate the usefulness of scanning probe microscopy as an adjunct to the other tools available for organic structure analysis, we used the natural product cephalandole A, which had previously been misassigned, and later corrected. Our results, corroborated by density functional theory, demonstrate that direct imaging of an organic compound with atomic-resolution force microscopy facilitates the accurate determination of its chemical structure. We anticipate that our method may be developed further towards molecular imaging with chemical sensitivity, and will become generally useful in solving certain classes of natural product structures.

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Figure 1: Structures derived from NMR data.
Figure 2: SPM measurements of the unknown compound.
Figure 3: Determination of the adsorption position.
Figure 4: Comparison of experimental and simulated AFM images.

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Acknowledgements

The authors thank K. Horikoshi for providing the Mariana Trench sediment, and A. Bull and M. Goodfellow for providing the Dermacoccus abyssi strain. Thanks also go to A. Curioni and R. Allenspach for discussions and comments. The research leading to these results has received funding from the European Community's projects HERODOT (grant agreement no. 214954) and ARTIST (grant agreement no. 243421) and the Swiss National Center of Competence in Research (NCCR) ‘Nanoscale Science’. W.M.A.M. received a PhD scholarship from the Egyptian government, and Aberdeen University provided instrument access. M.J. is the recipient of a BBSRC Research Development fellowship. The EPSRC National Mass Spectrometry Service provided the MS data. M.J. acknowledges S. Jaspars for bringing the work of the IBM team to his attention.

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Contributions

L.G., F.M. and G.M. performed the STM/AFM experiments. N.M. carried out the DFT calculations. R.E., W.M.A.M. and M.J. performed the NMR characterization and mass spectrometry. All authors contributed to the analysis of the data and the writing of the manuscript.

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Correspondence to Leo Gross.

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The authors declare no competing financial interests.

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Gross, L., Mohn, F., Moll, N. et al. Organic structure determination using atomic-resolution scanning probe microscopy. Nature Chem 2, 821–825 (2010). https://doi.org/10.1038/nchem.765

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