Monday, May 28, 2012

Olympicene's "Top Secret" Final Step

Over in London, preparations for the 2012 Summer Olympic games continue apace. The torch winds its way through the countryside, the ticket printers hum along, and the British Army has mounted defensive missiles on local apartment roofs. But, for those who've been missing the synthetic chemistry connection, wait no longer: enter, Olympicene!

Olympicene
Source: IBM Zurich | BBC
Olympicene, a tight five-ringed structure, does indeed resemble the famous logo of the quadrennial international contest. IBM Zurich, who used specially-functionalized AFM tips to image pentacene in 2009, now brings us fantastic high-res images of this polycycle (see right). 

I won't go into the story behind the science, as that's been elegantly summarized in a number of places already. Instead, I want to highlight a perplexing 'teaser line' from yesterday's ChemConnector post: 
"You can see the Olympicene compound coming together step by step and yes, the final step is not yet reported!" 
OK. Let's see, we have the first few steps laid out for us, thanks to RSC's ChemSpider. Easiest way to make anything? Start with most of it intact! From commercial 1-pyrenecarboxaldehyde, a Wittig olefination, H2 reduction, basic ester hydrolysis, chlorination, Friedel-Crafts, and lithium aluminum hydride (LAH) reduction brings us to the 5-ringed alcohol (shown below). All the steps are greater than 89% yield, except the F/C (15%), which one imagines might make the "other" pentacene isomer preferentially.


I find the final "Top Secret" step amusing, because any organic chemist "familiar with the art" could think of at least five ways to do it! (Non-chemist readers: the molecule on the left needs a single C=C double bond, and standing in the way is just a molecule of water). That alcohol is fairly "activated" for elimination. My guess? A little strong acid, gentle heat, and some molecular sieves.

Pro Tip: Don't believe the hype declaring olympicene the "smallest 5-ringed structure," at just 1.2 nm across. Skeptics, cynics should check their bond lengths. Is olympicene smaller than cubane? (6 rings, ~0.6 nm). How about a ladderane? (5 rings, ~1 nm). Anyone know other molecules that might qualify?


Updates (04:18, 5/29/12) - ChemConnector mentions, via Twitter, that the step is less 'Top Secret,' and more not-yet-drawn-up for ChemSpider Synthetic Pages. Per Excimer's comment, fixed the position of the 'saturated' CH2 carbon. 
(21:10, 5/31/12) - Commenter (And U. Warwick Prof!) Peter Scott points out the new ChemSpider page, showing major isomer and detailing conditions.

From the Vault: Scientific Humor, Shameless Plugs

I've been dying to use this photo.
Source: Nichelle Nichols
Holidays give you a chance to relax and reflect. Here in the States, we set aside time at the end of May to remember those who've served in our armed forces, past and present. Thanks to them, I'm able to bring you this glance back on my official 13-month blogging anniversary. (Well, 2 days late, but who's counting? Wait, you are? Nuts.)


Yes, back on April 26, 2011, Chemjobber was kind enough to lend me a little space to get this whole 'writting 4 de internetz' thing moving along. Over at The Haystack, Car1`men and Lisa didn't balk when I suggested that my first guest post involve Michael Jordan and Back to the Future. Paul didn't mind me poking a little fun at Wender's expense, and somewhere in July 2011, I had the crazy notion to hang out my own shingle.

Fast forward to late May 2012 - what a ride! I've met a bunch of new friends through Twitter and commenting on other blogs. I've been fortunate enough to appear at, and post on, sites I could have only dreamed of a year ago.

But, best of all? It's been a lot of fun!


To parrot the Ig Nobels slogan, I hope to make you laugh, then make you think. CJ and I goofed around with inflated yields in methods papers. When Breslow published his latest origin-of-life tract, it grew new life in the chemblogosphere as #spacedinos. How about art? Off-the-cuff projects included messing around with #arseniclife, pushing drawing memes, stitching together Easter eggs, "rosetta stone" chemical scribbles, and the 'Leaning Tower of Septa.'

'Olympicene,' viewed by STM.
Just in time for London 2012!
Source: IBM Zurich | U. Warwick
Wordplay? We got you covered. How about cute pharma diminutives? Mobile phone games, the Big Pharma Apocalypse, new chemistry portmanteaux, or silly chemical names? I also love finding molecular inspiration out in the wide world, whether it be on gas stations, at concerts, or imposing iron gates. I've even mused about taking this show on the road, once or twice.

I know I promised not to say anything yet, I'm grateful every day that interesting, excited, friendly readers - like you folks - stop by for awhile. I'll keep writing 'em, if you keep coming back.

Sunday, May 27, 2012

Confusing Toxibbreviations

Dr. Freddy, over at Synthetic Remarks, presented an interesting problem: why do so many molecules have such confusing abbreviations? If you think of an abbreviation as a linguistic shortcut, a way to save time while communicating complex ideas, it makes sense to use something everyone can understand. Unfortunately, the simplest workarounds can also be the most confusing; when I write "RM," do I mean 'recovered material,' or just an alkyl group attached to a catalyst? Depends on your audience.

The strangest shorthands? Natural product toxins.
Batrachotoxin: "Nothing like Brevetoxin."

For convenience, when chemists isolate a new biocide, they assign it a name ending in "toxin," which inevitably shortens to "TX." Pop another letter on the front to differentiate, et voila! (This probably made sense back when we'd found just a small handful of these compounds, but they're getting crowded now.)

Here's a few I tracked down, listed alphabetically:

ATX: Antillatoxin, Anenome toxin, Ammodytoxin, Altertoxin, Aflatoxin, Anatoxin, Adriatoxin
BTX: Botulinum toxin, Batrachotoxin, Brevetoxin
CTX: Charybdotoxin, Conotoxin, Cholera toxin, Ciguatoxin
DTX: Dendrotoxin, Dinophysistoxin, Diphtheria toxin
ETX: Epsilon toxin, Erabutoxin, Edema toxin, exotoxin
FTX: Funnel Web Spider Toxin
Nereistoxin: "Don't call me  Noxiustoxin!"
GTX: Gonyautoxin, Geographutoxin, Gambierotoxin, Gila toxin
HTX: Histrionicotoxin, Hemitoxin, Horridum toxin, Homoanatoxin
ITX: Iota toxin, Paralytic insecticidal toxin, immunotoxin
JTX: Joro spider toxin
KTX: Kaliotoxin
LTX: Latrotoxin, Leukotoxin, Anthrax Lethal toxin
MTX:  Maurotoxin, Maitotoxin, Maculotoxin, Mosquitocidal toxin
NTX: Nereistoxin, Noxiustoxin, neurotoxin
OTX: Ostreotoxin, Orphan toxin
PTX: Pertussis toxin, Palytoxin, Pectenotoxin, Pumiliotoxin
QTX: Quinquestriatus toxin
RTX: Repeat toxins
Saxitoxin: "Will the real STX please stand up?"
STX: Shiga toxin, Saxitoxin
TTX: Tetrodotoxin, Tetanus toxin
UTX: Uraemic toxins
VTX: Verotoxin, Verrucotoxin
WTX: Weak toxin (cobra), Waglerin
XTX: None found...open for business!
YTX: Yessotoxin
ZTX: Zetekitoxin, Zeta toxin

Readers - Have I left out your favorite poison or abbreviation? Let me know in the comments!

Wednesday, May 23, 2012

Close Enough for Chem - Guest Edition

Inspired by ChemBark's WWWTP series, I've asked friends of the blog to send me pictures of chemically-inclined art and logos from the wide world. Today, I bring you two more examples of so-close chemical structures.

Organo-'Catalyst' - This image, from a CT health center, contends that exercise can "catalyze" a better, healthier life. Well, that's a pretty strange-looking catalyst! Instead of your standard Pd or Ni, they've picked something approximating tryptamine. Honestly, the compounds that I think of when I see this structure don't necessarily encourage good health...


The "T" is for Texas Carbon - From a concert-goer in a college town comes this T-shirt (presented here without lifestyle endorsement). The tricyclic core of tetrahydrocannibol, an active component of marijuana, looks mostly OK, but the artist may have been under the influence when he drew that mixed-up hypervalent phenol ring!

Readers, have any more "almost" chemically-inspired photos? Feel free to send them my way!

Monday, May 21, 2012

Calimari Calligraphy: Same Ink, 160 Million Years Later

Old news: Geologists, digging up ancient British sea bed, unearth a fossilized cephalopod.


Big news: Its pigment sacs contain the same ink squid still use today!


Fossilized Ink Sac
Source: British Geological Soc. | Nat Geo
This archaeology, with a dash of chemistry for good measure, went to press in PNAS earlier today. As Nat Geo, Discovery News, and msnbc tell it, a stroke of luck brought the multi-national (Japan, India, USA, UK) team a fully intact ink sac, which still contained eumelanin, the ubiquitous black pigment found in skin, hair, and feathers throughout the biological world (for more on the structure and function of melanins, click here).  


Quoth the lead author, John D. Simon (UVA-Charlottesville), to Discovery
"Out of all of the organic pigments in living systems, melanin has the highest odds of being found in the fossil record" 
In other words, this collection of highly-oxidized tyrosine and indoleacetic acid residues, chained into polymeric pigments, stays preserved - and structurally sound - for 160 Million Years. Could we say that about most of the materials we make today? Moreover, by comparison of various spectral techniques, the authors wager that the ancient melanin composition looks nearly identical to what squid use today to scare off predators.


IR Data, "flipped"
Source: PNAS Supp Info
Well, I'd like to see some data, wouldn't you? Digging through the Supporting Info, I see loads of evidence: degradation studies, EPR, IR, Mass Spec, CHN analysis, Carbon-13 NMR, UV, pyrrolysis TIC, and X-Ray photoelectron spectroscopy (Whew!). 


Let's examine two of these a little closer. For the IR data, I've switched the view around 180 degrees, to present the peaks the way you'd normally see 'em in the lab. Note the top 2, calcium carbonate and hydroxyapatite, with their nice, sharp C=O and P=O stretching bands. When the researchers looked in the partially-fossilized sediment, they found mostly these two...but look at the dye! Even after all those millennia, the absorbances for the fossil dye line up almost perfectly with the modern-day sample.


Total Ion Chromatogram, Current (top) vs. Fossil (bottom)
Source: PNAS Supp Info
How about a little heat? If you cook the ink at 600 Celsius, then pass it quickly through a mass spec, plotting ion current vs. time, you get the next spectrum, the TIC. It shows the same breakdown products, a variety of small heterocycles and fatty acids, and something I wasn't familiar with: diagenetic products. These products, formed from reactions that occur during fossilization, show up here as sulfur heteorcycles. Since the samples have had quite a bit of time underground, they show much more diagenetic decomposition. 

Sunday, May 20, 2012

Sunscreen Chemophobia: Oxybenzone

(I wrote this for participation in the 2012 'Toxic Chemicals' Blog Carnival, over at ScienceGeist)


This 'suit' wants to sneak more chemicals into your sunscreen!
Source: EWG 'Hall of Shame'
Courtesy of Mother Jones and the Environmental Working Group (EWG), we can all breathe a bit easier. The eco-conscious nonprofit organizations have just released their recommendations for summer sunscreens. Unsurprisingly, the Top 20 are cut from the same cloth; words such as "natural," "clear," "garden," and "organic" abound. Ingredients, too: ~20% or so of 'micronized' (>100 nm) zinc oxide, some titanium dioxide for good measure . . .and just about every fruit oil, tea extract, or skin moisturizer you can think of.

Actually, I found myself much more drawn to the 'Hall of Shame.' These sunscreen outlaws represent all the nefarious tricks #BigChem might play on an unsuspecting public - sneaking in oxybenzone, "nano-zinc," and retinyl palmitate (synthetic Vitamin A) to make a buck off naive customers. I won't weigh in on the last two ingredients, but oxybenzone certainly caught my eye.

Oxybenzone, also called benzophenone-3, finds its way into sunscreen, lipstick, lotions, paints, and polymers. According to the Merck Index, it was first prepared over a century ago (1906), and patents from the 1950s show a simple one-step prep, Friedel-Crafts acylation of benzoyl chloride, which forms the new C-C bond between the "left" aromatic ring and the C=O group. Oxybenzone actually absorbs UV light over a wide swath of the spectrum, from 280-320 nm, meaning it offers sun protection from both UV-A and UV-B.

oxybenzone
The EWG calls oxybenzone a "hormone-disrupting chemical." Like bisphenol A (BPA), another well-reported and contentious molecule, oxybenzone contains a free phenol group, and two aromatic rings linked by a central carbon bridge. These atomic features tend to crop up in compounds that mimic estrogens in the body.

Well, does oxybenzone pose endocrine risks? Where could you find that info, anyway?

I started where I usually do: TOXNET, the U.S. National Library of Medicine reference database. Oxybenzone triggers six references from the Developmental Toxin (DART) literature, which cover 18 years of studies on fish, mice, and cell cultures. I also checked PubMed, grabbed a 1992 National Toxicology Program (NTP) oxybenzone report, and the 2008 European Commission SCCP recommendations for consumer exposure.

What do the data show? At the highest doses - 50,000 ppm - all animals develop liver, kidney, and reproductive organ damage. But the dose makes the poison, and as you feed (oral) or rub on (dermal) less compound, the side effects fall off rapidly. No teratogenicity (fetal harm), no mutagenicity (DNA errors), and no unexplained deaths. The scientists did observe indications of "moderate reproductive toxicity," but, again, these showed up in the highest-dose groups. To replicate these effects in humans, you'd have to literally eat spoonfuls of the compound (For ongoing oxybenzone studies, see: NTP, CDC).

The European Union, exemplars for cautious chemical regulation, provide a convenient calculation for human exposure: for a standard 60 kg (132 lb) person, given skin absorption, sunscreen concentration (6% oxybenzone), and average application at 18 g (just over half an ounce), exposure = 1.78 mg / kg / body weight / day. That's ~2 ppm, fully 500 times less than the lowest doses currently testing at the NTP (see above). The 2008 EU panel assigns oxybenzone a Margin of Safety of 112; compounds above 100 generally meet their benchmark for safe use.

Delicious cup of low-dose,
 bioactive compounds
Source: Green Tea Health
But, hormones influence body chemistry at miniscule doses, right? And, these sunscreen compounds are ubiquitous! How can we be absolutely certain that they aren't toxic? Well, I'll counter with a simple observation: herbal, plant, and seed extracts - like the shea butter, aloe juice, camellia seed oil, jojoba, calendula, papaya, plantain leaf, starflower seed, linseed oil, green tea extract, olive oil, plankton, avocado oil, primrose oil, and bark extracts found in the "alternative" sunscreens - have just as many, if not more bioactive compounds!

For chemophobic consumers, the general (albeit, flawed) reasoning seems to go something like this:
Many small, aromatic, heteroatom-containing molecules may be endocrine disruptors.
Industrial companies produce many such chemical compounds.
Therefore, many "industrial" chemicals cause health problems.
Magically, however, this logical logjam clears if you mention "natural," "organic," or "chemical-free" formulations. I suspect the reasoning goes:
Many small, aromatic, heteroatom-containing molecules may be endocrine disruptors.
Natural product extracts contain dozens of compounds, some unknown, many untested.
But, since they're from plant extracts, they're probably safe.
Would consumer impressions of oxybenzone change if it were. . .a natural plant extract? Good news: it is.

That's right, the compound occurs naturally in various flower pigments, which chemically trained eyes might have detected in the "resorcinol-like" framework. To stretch the metaphor, given the eased FDA rules regarding dietary supplements, I wonder if one could employ this tactic to produce a "natural, plant-based sunscreen" that still contains oxybenzone!

Happy summer, everyone! Think clearly, ask questions, and challenge assumptions. And, wherever you buy it from, remember to always wear your sunscreen.

For a different perspective on EWG's sunscreen data, head over to Science-Based Medicine

Saturday, May 19, 2012

"Hot Rocks" Cause Injury, Mystery

As reported on Yahoo / GMA (video), and by the ever-vigilant Jyllian Kemsley over at Safety Zone, a real-life chemical mystery is unfolding. A few days ago, a California couple strolled the beach with their kids, and pocketed a few interesting-looking rocks they had found. Later that evening, the rocks caught fire while in Lyn Hiner's pants pocket, with a "...bright, intense flame," that, according to reports, couldn't be patted or smothered out. The resulting fire hospitalized both wife and husband with severe burns.

Source: AP
So, the question remains: what was on the rocks? The orange substance, found on green and gray surfaces, may indeed be "phosphorous" [sic], as mentioned by a mildly chemophobic (nearby nuclear plant, firing range?!) Associated Press report. A local geologist commented that the orange coloration is "...not natural, it's human made." With some imagination, you could probably come up with a few phosphorus alternatives (looking at you here, ExploSci!).

Pyrophoric Metals - Finely dispersed powders of magnesium, zinc, or thermite could certainly react with a little acid or moisture. However, these don't fit the bill as "orange substances."


Flash powder - Often used in special effects and flares. This blend of oxidizers and reactive metals would have to have been intentionally placed on the rocks, since they wouldn't have remained stable for long, out in the open air.


Reactive Groups - Many organic groups react with violent decomposition or exotherms when sparked, touched, or heated. Although certainly far-fetched, someone fooling around with picrates, nitrates, or perchlorates could have inadvertently doped the stones in question. There's at least a few dozen of these salts around, and many (iron perchlorate, mercury fulminate, ammonium picrate) may actually be orange or yellow-colored.