Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

I wrote not long ago about another use of atomic force microscopy images to determine chemical structures, and now here’s another paper on the same general topic. Pretty soon, this is going to become too common to note, and structure determination will have changed forever (once again!)

Shown are some asphaltenes – and if you’ve never had to think about asphalt from a chemical point of view, maybe you’re lucky. It’s a real brew of high-molecular-weight hydrocarbons and heterocycles, and these are just a few of them. There’s been a lot of analytical chemistry done on these systems over the years (there are more compounds in there to separate than you’d want to think about), but even once you’ve separated them, figuring out the structures is what the folks at the bench call “nontrivial”. You can get a molecular weight by blasting away with the mass spec machines, but there are a lot of possible structures per molecular weight up in that range, and these kinds of molecules tend to look very, very similar by NMR and optical spectroscopy. (Here’s a recent review).

These things are perfect candidates, though, for AFM. The authors have taken an asphalt mixture and scattered it onto a surface of sodium chloride crystal layered onto copper, and then just scanned around the surface, picking out one molecule after another. Three representatives are shown; the paper has over a hundred in total. Comparing material from different sources also shows different patterns in the structural classes, as you might expect, opening up a whole new area for fingerprinting such samples. I’d guess that almost all the molecules in this paper are new to science, in the sense of having been described as separate entities (you could draw such stuff on a whiteboard all day long, if you were so minded). And they look even flatter and less soluble than the drug candidates I’ve worked on over the years, which (in a few cases) is really saying something!