The Fujita group has a new paper out on their “crystalline sponge” method for X-ray structure determination. I had the chance to hear Prof. Fujita speak on this recently – a very interesting talk indeed – and I’ve been looking forward to the paper. (Here’s a summary from an equally impressed Quintus).
This time, they’re looking at oxidation reactions of the cyclic terpene humulene. That compound, as a glance at its structure will indicate, is not a crystalline solid, but it soaks into the zinc-containing metal-organic framework just fine. And so do all the epoxide and aldehyde oxidation products when the starting material is treated with MCPBA or selenium dioxide. These structures would not be a lot of fun to figure out from NMR data alone, but the X-ray sponge technique nails them all down.
During his seminar, Fujita said that it’s been his experience that if a parent structure fits will into the metal-organic frameworks, that derivatives of it tend to have much higher success rates as well, and that seems to have been the case here. (The overall success rate, from all sorts of structures, is lower). But I’m not surprised that it doesn’t work every time – what continues to surprise and delight me is that it works as well as it does.
One source of tension during the advent of this technique has been the crystallographic rigor of the results. Crystallographers are nothing if not rigorous with their data – if you’re not, you can get lost so many ways that it’ll make your head spin. (That especially goes for protein/ligand crystals, which are very rarely obtained with the resolution of small molecules). The “crystalline sponge” technique is sort of in-between: protein crystallographers look at it and say “Hmm, not so bad”, while small-molecule crystallographers are more doubtful, especially when they see use of solvent-exclusion routines and other data-cleanup techniques. But the recent guidelines proposed by the Clardy group have probably helped in that regard.
I’m no crystallographer myself, but looking over the Supporting Information file for this paper, I note that it details when crystallographic restraints had to be used during the various structure refinements, which is welcome. You can also see that the group did a lot of refinement of the crystal soaking conditions for each compound, which is something that Fujita emphasized during his seminar as well. Interestingly, in one of the complexes, an impurity showed up also ordered in the crystalline framework, which is probably a phthalate plasticizer (leached out of labware). There’s a possibility that it’s a disordered nitrobenzene, a solvent used to produce the crystals initially, but an infrared spectrum of the crystals showed CO bands. (Clardy’s procedure for making the crystals dispenses with the nitrobenzene entirely, so it’ll be worth watching to see if phtalates show up from that recipe once in a while, too).