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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« Making the Non-Flat, Non-Aromatic Compounds | Main | A Total Synthesis Archive »

May 31, 2013

Check Out These Molecules

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Posted by Derek

It's molecular imaging week! See Arr Oh and others have sent along this paper from Science, a really wonderful example of atomic-level work. (For those without journal access, Wired and PhysOrg have good summaries).
Arylenes.jpg

As that image shows, what this team has done is take a starting (poly) phenylacetylene compound and let it cyclize to a variety of products. And they can distinguish the resulting frameworks by direct imaging with an atomic force microscope (using a carbon monoxide molecule as the tip, as in this work), in what is surely the most dramatic example yet of this technique's application to small-molecule structure determination. (The first use I know of, from 2010, is here). The two main products are shown, but they pick up several others, including exotica like stable diradicals (compound 10 in the paper).

There are some important things to keep in mind here. For one, the only way to get a decent structure by this technique is if your molecules can lie flat. These are all sitting on the face of a silver crystal, but if a structure starts poking up, the contrast in the AFM data can be very hard to interpret. The authors of this study had this happen with their compound 9, which curls up from the surface and whose structure is unclear. Another thing to note is that the product distribution is surely altered by the AFM conditions: a molecule in solution will probably find different things to do with itself than one stuck face-on to a metal surface.

But these considerations aside, I find this to be a remarkable piece of work. I hope that some enterprising nanotechnologists will eventually make some sort of array version of the AFM, with multiple tips splayed out from each other, with each CO molecule feeding to a different channel. Such an AFM "hand" might be able to deconvolute more three-dimensional structures (and perhaps sense chirality directly?) Easy for me to propose - I don't have to get it to work!

Comments (21) + TrackBacks (0) | Category: Analytical Chemistry | Chemical News


COMMENTS

1. Model on May 31, 2013 8:30 AM writes...

beautiful

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2. student on May 31, 2013 10:33 AM writes...

Fucking awesome

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3. anon biochem on May 31, 2013 10:46 AM writes...

I feel like this and the previous hydrogen atom images are going to be a staple of chemistry textbooks for decades.

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4. Wile E. Coyote, Genius on May 31, 2013 12:44 PM writes...

Why the foul language? Can't someone express awe without being crude and vulgar? I think it was Shaw (paraphrase) that said that someone that finds it necessary to use vulgarities is only compensating for a sorely deficient vocabulary. I've seen heated debates here, but very infrequently the foul language. I really like the class (generally) of the responders to this blog.

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5. MoMo on May 31, 2013 1:32 PM writes...

Look at the Acetylenes! Spectacular! They look like little Balls of electron density!

Can I say "Balls" Wile E. Coyote? And don't go quoting Shaw and scaring off Students new to this blog with Oyster Bay blueblood mannerisms.

Shaw was a drunken Irishman, into eugenics and anti-science and medicine, and I am sure said worse.

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6. nitrosonium on May 31, 2013 2:01 PM writes...

in no way am i questioning the work or integrity of the researchers but i always wonder with these things if knowing what you're looking for in anyway biases how the data is processed or enhanced (colored/grey scaled) to give a final image. in other words...if you gave them an "unknown" would they get these beautiful images that look just like the chemdraw structures??

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7. C.W. Boghorne on May 31, 2013 2:03 PM writes...

Student: less than eloquent, but no crime.

Wile. E. Coyote: sanctimonious scrote.

Please find the wherewithal to distinguish between style and content.

Behave yourselves.

CWB.

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8. pete on May 31, 2013 2:25 PM writes...

stunning stuff -- and effin' awesome, too.

as defined by CRUACPISS: The Committee to Regulate The Use of Awesome & Cussword-Proxies In The Same Sentence

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9. Wile E. Coyote, Genius on May 31, 2013 2:25 PM writes...

@ C.W. Great, so now we're into name calling. I still really do believe that the quality of Derek's blog draws a higher class of commenter (generally). And you're right, nothing criminal in the use of the words previously expressed, but why not be civil instead of crude? There's too much unpleasantness in this world as it is, why contribute? And why not admonish when seen? If that make me sanctimonious, I guess I'll wear that appellation with pride. I'm done with this thread as it is now way off topic.

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10. Sisyphus on May 31, 2013 9:38 PM writes...

What is the difference between a summary and infringing on a copyright?

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11. student on June 2, 2013 3:28 PM writes...

I think Stephen Fry puts swearing in perfect context:
https://www.youtube.com/watch?v=icLZGGNKKfE

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12. Li on June 2, 2013 6:47 PM writes...

Just awesome!
As far as the crude language: It is offensive to some people. Does anybody here not know that?! Do some here really believe its ok to knowingly offend people unnecessarily? In case people need potty-mouth training (and believe me I have one), it is inappropriate in public discourse.
I once made the mistake in a internal sales meeting of saying that the problem was "not in the fucking product" in an attempt to add emphasis. I offended the Vice President of Sales (among others).
He often alluded to it (even 3 years later). Civility requires appreciation of AND respect for diversity. Take a hint.

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13. Anonymous on June 3, 2013 5:35 AM writes...

"sanctimonious scrote" - sorry, but that did make me laugh.

Wonderful, mind-blowing images. As someone who spent a few years hunched over these temperamental pieces of equipment I can only imagine how much blood, sweat and tears went into obtaining these.

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14. Anonymous on June 3, 2013 5:57 AM writes...

Derek,

excellent 2D molecules after 3D ones from last week.
Room for every and all kinds of molecules within the chemistry space!
By the way, I love 3D, but deeply impressed by these 2D pictures

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15. Jonathan on June 3, 2013 8:50 AM writes...

I think the only appropriate response to the topic of foul language is this one:

https://www.youtube.com/watch?v=cf9erulmi_4

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16. barry on June 3, 2013 10:19 AM writes...

at the risk of seeming hopelessly naive--I don't get it. Why is no structure visible in the silver substrate? What does "smooth" mean in the context of a technique that can resolve atoms?

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17. Electrochemist on June 3, 2013 12:29 PM writes...

@#16, barry - The short answer is that they used a single CO molecule adsorbed on an AFM tip at low temperature and thus only detected interactions between the tip and other C-atoms.

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18. barry on June 3, 2013 1:23 PM writes...

@#17
and silver atoms are magically invisible to a CO probe? That seems like less than an explanation.
I know that a "smooth silver surface" is commonplace in these accounts. But I very much want to understand what that means.

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19. Derek Lowe on June 3, 2013 1:32 PM writes...

Barry, one factor is that the CO tip is ratched down far enough to start interacting with the electron clouds around the adsorbed molecules, but not so far that it detects anything from the silver surface. You can certainly see the silver plane if you go down far enough.

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20. Electrochemist on June 3, 2013 1:47 PM writes...

@ Barry and Derek - There is a better description in an earlier Science paper of the modified tip AFM technique and the origin of the image contrast (See: SCIENCE 28 AUGUST 2009, VOL 325, p. 1110). The quantity being measured in these experiments is the change in resonance frequency of the AFM tip (delta f). They adsorb a single CO molecule with the oxygen oriented towards the sample molecule at 7 deg K. There is no measurable change in frequency when moving from one region of the underlying Ag substrate to another. Only when a C-containing molecule interacts with the adsorbed CO is an image ("contrast") registered.

BTW: I would be interested in a reference demonstrating that "You can certainly see the silver plane if you go down far enough."

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21. Derek Lowe on June 3, 2013 2:55 PM writes...

#20, Electrochemist. I'm probably thinking of STM versus AFM. Here's an image of iron atoms on a silver plane, using a CO tip with an STM. See Figure 4:

http://www.sciencemag.org/content/286/5445/1719.full

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