How many ways do we have to differentiate samples of closely related compounds? There's NMR, of course, and mass spec. But what if two compounds have the same mass, or have unrevealing NMR spectra? Here's a new paper in JACS that proposes another method entirely.
Well, maybe not entirely, because it still relies on NMR. But this one is taking advantage of the sensitivity of 19F NMR shifts to molecular interactions (the same thing that underlies its use as a fragment-screening technique). The authors (Timothy Swager and co-workers at MIT) have prepared several calixarene host molecules which can complex a variety of small organic guests. The host structures feature nonequivalent fluorinated groups, and when another molecule binds, the 19F NMR peaks shift around compared to the unoccupied state. (Shown are a set of their test analytes, plotted by the change in three different 19F shifts).
That's a pretty ingenious idea - anyone who's done 19F NMR work will hear about the concept and immediately say "Oh yeah - that would work, wouldn't it?" But no one else seems to have thought of it. Spectra of their various host molecules show that chemically very similar molecules can be immediately differentiated (such as acetonitrile versus propionitrile), and structural isomers of the same mass are also instantly distinguished. Mixtures of several compounds can also be assigned component by component.
This paper concentrates on nitriles, which all seem to bind in a similar way inside the host molecules. That means that solvents like acetone and ethyl acetate don't interfere at all, but it also means that these particular hosts are far from universal sensors. But no one should expect them to be. The same 19F shift idea can be applied across all sorts of structures. You could imagine working up a "pesticide analysis suite" or a "chemical warfare precursor suite" of well-chosen host structures, sold together as a detection kit.
This idea is going to be competing with LC/MS techniques. Those, when they're up and running, clearly provide more information about a given mixture, but good reproducible methods can take a fair amount of work up front. This method seems to me to be more of a competition for something like ELISA assays, answering questions like "Is there any of compound X in this sample?" or "Here's a sample contaminated with an unknown member of Compound Class Y. Which one is it?" The disadvantage there is that an ELISA doesn't need an NMR (with a fluorine probe) handy.
But it'll be worth seeing what can be made of it. I wonder if there could be host molecules that are particularly good at sensing/complexing particular key functional groups, the way that the current set picks up nitriles? How far into macromolecular/biomolecular space can this idea be extended? If it can be implemented in areas where traditional NMR and LC/MS have problems, it could find plenty of use.