Determining the structure by looking at the molecule


ResearchBlogging.orgIn many cases it is notoriously difficult to determine the exact structure of a molecule, especially with larger ones. Stereocenters tend to make things worse, and interesting molecules tend to have several of them. Have you ever sat up to the neck in a pile of inconclusive spectra and wished you could just hold it and see the molecule just like in those colored balls-and-sticks-models everyone likes to draw in their papers?

Well, take hope. You may remember the snapshots taken of pentacene molecules a while ago by atomic force microscopy that, surprisingly, looked exactly like pentacene? The ones where you could see that the rings at the ends were slightly lifted up, because the interactions with the surface were stronger in the middle of the molecule?

The group that did those images is at it again, and this time they tried something a little more complicated this time. The target molecule, cephalandole A, already hat it’s structure determined – wrongly, as it turned out, as the first structure had to be corrected.

Source: Gross, L. et al., Organic structure determination using atomic-resolution scanning probe microscopy. Nature Chemistry 10.1038/nchem.765, 2010.

The result is of course not as intuitive as that of pentacene, where electron density closely follows the molecular scaffold. A molecule with several different functional groups has a far greater variation in electron density and it shows in the image. Nevertheless you can still see parts of the actual structure.

Even better, the researchers could use this representation to identify the correct molecular structure from the four possible variants that the original NMR Data could not distinguish. So even at this early stage, the technique can be used to solve actual structure determination problems. Expect the technique to improve quickly, as NMR did. This may well change the way we determine molecular structures forever.

Speaking of change, the image had me thinking: What will this do to our perception of chemical molecules, and to the way we draw them? Chemists never had images of molecules, so they had to devise ways to show their important characteristics from scratch. That’s how we arrived at lines linking balls or letters, or, on a slightly more sophisticated level, bulgy van-der-Waals surfaces and the like.

But the molecules created by this technique don’t look like that. What comes out of the atomic force microscopy is far more real, in a chemical sense, because the tip of the cantilever measures something that actually determines chemical behavior. So the cephalandole A published by Gross et al. looks weird and unfamiliar at first, but maybe this is because we used to draw them in the wrong way. Maybe this is how chemists should draw such molecules, at least in some way.

I believe as the technique progresses and becomes more commonplace, the power of images alone will make it happen.

Gross, L., Mohn, F., Moll, N., Meyer, G., Ebel, R., Abdel-Mageed, W., & Jaspars, M. (2010). Organic structure determination using atomic-resolution scanning probe microscopy Nature Chemistry DOI: 10.1038/nchem.765

2 Responses to “Determining the structure by looking at the molecule”

  1. Neuroskeptic Says:

    That’s some amazing work.

    I don’t see the new image as that counter-intuitive – on the contrary I’m amazed at how similar it is to a lines-and-letters structure. They’re not just abstract representations, they’re actually pretty good representations! But then I’m not a chemist…

  2. Lars Fischer Says:

    It takes some getting used to, but yes, you’re right. You have to detach yourself from the instinct to see only the red parts as belonging to the molecule.

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