Tracking Reactions? AFM FTW

Thanks to @slugnads at Wired for pointing out this story!
Update 5/31/13 - Derek's also got a great review going at Pipeline.

Remember 2009, when you gasped for a moment at the beautiful IBM structure of pentacene? 

Credit: BBC News | IBM | Science

In 2012, just in time for the 2012 London Olympics, the same team helped to image "olympicene."

Credit: BBC | IBM

And now, just 5 months into 2013, a team of researchers from UC-Berkeley / LBNL and several physics institutes in Spain have watched cyclizations occur on silver surfaces, using AFM tips to detect the ghostly products in stunning resolution:

Credit: Science | LBNL | UC-Berkeley | Wired

HOLY. COW.

As if this couldn't sound any more amazing, the researchers were able to predict and visualize several products previously predicted by theory, but never directly observed (stabilized diradicals, anyone?). 

So, will this be a standard technique for the practicing chemist? I'm guessing not for quite a few years, since the hardware involved still isn't commonplace, and the technique probably works best at prohibitively high dilutions with flat molecules. Med chem? Sure, you could watch a Suzuki coupling occur, or watch a Cope rearrangement, but for "3D" molecules (read: alkaloids, vitamins, sugars, etc...) I think NMR and X-ray crystallography will still be your best bets. 

But to paraphrase the futurists, predictions ironically suffer from poor foresight - after all, just over a month ago, a Japanese group disclosed how to take on-demand crystal structures of just about anything. So, I'm sure someone will invent a "rugged" surface capable of guiding the AFM tip around points and curves to monitor, say, real-time Pictet-Spengler reactions. Can't wait!

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.