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:

1. A novel alkaloid, xinghaiamine A, isolated from a marine bacterium, that...
2. Had novel structural features, such as a sulfoxide and acenaphthylene ring, rarely seen, and...
3. 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:

Jiao, Zhang, Zhao, Hu, Suh, PLoS One, 2013

[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:

Xinghaiamine A, pseudo-axial conformation,
assumed diastereomer of the (4-4-5-6) ring system.
The red circles are supposed to be bonded together...

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:

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:

Potential editing of the H/H COSY

...and the HMBC

The Future is Now

The Graf Zeppelin. Source: Ad Orientem

I’ll admit it: I love to look at antiquated predictions of how the world will be in 50 or 100 years. These glimpses into the future strongly reflect their era; the audience had to grasp the author’s intent and direction using metaphors and extensions of the technology they knew. 


We chuckle at predictions such as world zeppelin travel and automated horse-carriages, much like future generations might wrinkle their noses at our notion of a “world wide web” or “smart phones.”

A new (old!) article, published in the 1901 Ladies’ Home Journal by one John Elfreth Watkins, Jr., puts forth several such predictions (thanks to the Saturday Evening Post and the BBC; see reddit or imgur for the full article). Mr. Watkins apparently spoke with “the wisest and most careful men in our greatest institutions of science and learning” in a quest to determine what “…will have been wrought…before the dawn of 2001.”

All told, Mr. Watkins made 28 predictions in his article, and the BBC article covered 14, the Post 17. Since this is primarily a science blog, I’ll comment on some of the tech highlights; sadly, most of these didn’t make the cut for the preceding articles.

The drug designer's "killer app"

 “Few drugs will be swallowed or taken into the stomach” – Drug designers, aiming always for the killer app of oral availability, would be amused to hear this. The author was correct about a later statement in this section, though: “The living body will to all medical purposes be transparent.” Mr. Watkins waxes about invisible rays allowing physicians to operate on human organs directly, which, with the advent of MRI, PET scans, and endoscopy, is much closer to reality.

“…utensils shall be washed in chemicals fatal to disease microbes” – Antibacterial hand soaps, bleach, and wastewater sanitation systems maintain healthy conditions in large restaurants.

“There will be no C, X, or Q in our every-day alphabet” – Uh-oh, don’t tell any organic chemists! C is, of course, carbon, and X is a placeholder for halogens, a math variable, part of road signs (X-ing), holidays (Xmas), and of course where pirates bury their treasure!

“The soil will be kept enriched by plants which take their nutrition from the air and give fertility to the earth” – Nitrogen fixation, anyone? Legumes such as peas, beans, and carob are often rotated in with other food crops to ensure proper soil nutrients. In 1901, Watkins still had no inkling of the Great War to come, or how the Haber-Bosch process would lead to cheap fertilizers and increased munitions.

Might there be a Schrock-Chirik process in our fixation future?

“Plants will be made proof against disease microbes just as readily as man is to-day against smallpox” – Mr. Watkins refers, of course, to Jenner’s development of the cowpox vaccine for smallpox treatment. In the 21^st Century, industrial conglomerates such as Dow Agro, DuPont Crop Science, BASF, Syngenta, and Monsanto work towards pest-resistant crops and pesticides.

An FDA inspector checks a salad bar. Source: FDA Flickr.
(Did you know the FDA maintains a Flickr account? I didn't!)

 “Storekeepers who expose food to air breathed out by patrons or to the atmosphere of the busy streets will be arrested with those who sell stale or adulterated produce” – The modern FDA, presaged 5 years before its formation in 1906, now inspects both food and drugs from production through sale to consumers.