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.

Dermacoccus abyssi sp. nov., strains MT1.1 and MT1.2 are actinomycetes isolated from Mariana Trench sediment at a depth of 10 898 m. Fermentation using ISP2 and 410 media, respectively, lead to production of seven new oxidized and reduced phenazine-type pigments, dermacozines A-G (1-7), together with the known phenazine-1-carboxylic acid (8) and phenazine-1,6-dicarboxylic acid (9). Extensive use was made of 1D and 2D-NMR data, and high resolution MS to determine the structures of the compounds. To confirm the structure of the most complex pentacyclic analogue (5) we made use of electronic structure calculations to compare experimental and theoretical UV-Vis spectra, which confirmed a novel structural class of phenazine derivatives, the dermacozines. The absolute stereochemistry of dermacozine D (4) was determined as S by a combination of CD spectroscopy and electronic structure calculations. Dermacozines F (6) and G (7) exhibited moderate cytotoxic activity against leukaemia cell line K562 with IC(50) values of 9 and 7 microM, respectively, while the highest radical scavenger activity was observed for dermacozine C (3) with an IC(50) value of 8.4 microM.

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