Spot-Checking Antibacterials in PLoS One
Update (April 17) - Commenters here and at Derek's place have set off alarm bells to potentially doctored spectra. Stay tuned...
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Ever looked at a molecule and thought something was just...off?
A little while ago, I browsed through the latest edition of PLoS One, the open science journal. I don't often go there for chemistry publications, but curiosity struck, so I typed, "antibacterial NMR" (I think) into the search box. Up came this paper, from 2013, announcing:
[Rubs eyes in disbelief].
Sulfonylated "ladderane" substructure.
A (4,7) disubstituted acenaphthylene bridge.
A previously-unknown-to-science (and virtually unknown to SciFinder) 4-4-5-6 ring system.
Can that really be correct?
Naturally, I made a model of one "half" of the presumed dimeric molecule:
I've taken apart and reassembled this molecule a few times, and can't seem to access any diastereomer that 1) looks energetically minimized, and 2) can actually have the acenaphthylene bridge the way the authors specify without "strain energy" popping out the plastic bonds.
Perusing the analyticals in the Supporting Information, I'm puzzled by a few more bits:
The IR, briefly addressed in the text as suggestive of "[the] presence of a sulfoxide functional group" due to the 1082 cm-1 band, but contains peaks suggestive of:
--
Ever looked at a molecule and thought something was just...off?
A little while ago, I browsed through the latest edition of PLoS One, the open science journal. I don't often go there for chemistry publications, but curiosity struck, so I typed, "antibacterial NMR" (I think) into the search box. Up came this paper, from 2013, announcing:
- A novel alkaloid, xinghaiamine A, isolated from a marine bacterium, that...
- Had novel structural features, such as a sulfoxide and acenaphthylene ring, rarely seen, and...
- That showed decent lead activity against MRSA strains (2.7-5.5 uM MIC).
First thought: "Wow!" Second thought: "If this is so great, why is it buried in PLoS One?"
Then I happened to look at the proposed structure for this potential panacea:
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| Jiao, Zhang, Zhao, Hu, Suh, PLoS One, 2013 |
Sulfonylated "ladderane" substructure.
A (4,7) disubstituted acenaphthylene bridge.
A previously-unknown-to-science (and virtually unknown to SciFinder) 4-4-5-6 ring system.
Can that really be correct?
Naturally, I made a model of one "half" of the presumed dimeric molecule:
 |
| Xinghaiamine A, pseudo-axial conformation, assumed diastereomer of the (4-4-5-6) ring system. The red circles are supposed to be bonded together... |
Perusing the analyticals in the Supporting Information, I'm puzzled by a few more bits:
 |
| Jiao, Zhang, Zhao, Hu, Suh, PLoS One, 2013 |
The IR, briefly addressed in the text as suggestive of "[the] presence of a sulfoxide functional group" due to the 1082 cm-1 band, but contains peaks suggestive of:
- alcohols, primary amines: 3383 cm-1 band
- heteroaromatics: 743, 846 cm-1 band
The published 1H NMR has no peak labeling or integration (tsk, tsk).
That the COSY shows only one set of strong H/H correlations out of the 6 posited protons on the conjugated ring, which should not fit with the proposed structure. Nor should the seeming high symmetry of the ring fit with the proposed substitution.
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Readers, what do you make of this? What kept this out of a more mainstream chemistry journal?
Do you agree with the assigned structure? (Am I just shouting in the wind here?)
April 17 - Uh-oh...check out these anonymous commenters' finds on Derek's blog:
April 17 - Uh-oh...check out these anonymous commenters' finds on Derek's blog:
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| Potential editing of the H/H COSY |
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| ...and the HMBC |
