Fluorine NMR is underused in chemistry. Well, then again, maybe it's not, but it's one of those thing that just seems like it should have more uses than it does. (Here's a recent bookon the subject). Fluorine is a great NMR nucleus - all the F in the world is the same isotope, unless you're right next to a PET scanning facility - and the different compound show up over a very wide range of chemical shifts. You've got that going for you, coupling information, NOE, basically all your friends from proton NMR.
There's a pretty recent paper showing a good use of all these qualities (blogged about here at Practical Fragments as well). A group at Amgen reports on their work using fluorine NMR as a fragment-screening tool. They can take mixtures of 10 or 12 compounds at a time (because of all those different chemical shifts) and run the spectra with and without a target protein in the vial. If a fragment binds, its F peak broadens out (you can even get binding constants if you run at a few different concentrations). A simple overlay of the two spectra tells you immediately if you have hits. You don't need to have any special form of the protein, and you don't even need to run in deuterated solvents, since you're just ignoring protons altogether.
Interestingly, when they go on to try other assay techniques as follow-up, they find that the fluorines themselves aren't always a key part of the binding. Sometimes switching to the non-fluorinated version of the fragment gives you a better compound; sometimes it doesn't. The binding constants you get from the NMR, though, do compare very well to the ones from other assays.
The part I found most interesting was the intra-ligand NOE example. (That's also something that's been done in proton NMR, although it's not easy). They show a case where 19F ligands do get close enough to show the effect, and that a linked version of the two fragments does, as you'd hope, make a much more potent compound. That's the sort of thing that fragment people are always wanting to know - what fits next door to my hit? Can they be linked together? Fragment linking has its ups and downs, going back to the Abbott SAR-by-NMR days. That was a technique that never really panned out, as far as can be seen, but this is at least an experimentally easy way to give it a shot. (Of course, the chances of the fluorines on your ligands actually being pointed at each other is probably small, so that does cancel things out a bit).
Overall, it's a fun paper to read - well, allowing for my geeky interests, it is - and perhaps it'll lead a few more people to think of things that could be done with fluorine NMR in general. It's just sitting there, waiting to be used. . .