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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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March 7, 2014

A Structure From the Molecular Sponge

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Posted by Derek

There's an interesting report from the Buchwald group using the Fujita "molecular sponge" crystallography technique. The last report on this was a correction, amid reports that the method was not as widely applicable as had been hoped, so I'm very happy to see it being used here.

They're revising the structure of a new reagent (from the Lu and Shen groups in Shanghai) for introducing the SCF3 group. It was proposed to be a hypervalent iodine (similar to other reagents in this class), but Buchwald's group found some NMR data and reactivity trends that suggested the structure might be in the open form, rather than the five-membered iodine ring one.

Soaking this reagent into the MOF crystal provided a structure, although if you read the supporting information, it wasn't easy. The compound was still somewhat disordered in the MOF lattice, and there were still nitrobenzene and cyclohexane solvent molecules present. The SCF3 reagent showed up in two crystallographically independent sites, one of them associated with residual nitrobenzene. After a good deal of work, though, they did show that open-form structure was present. (The Shen et al. paper's conclusions on its synthetic uses, though, are all still valid; it's just the the structure doesn't fall into the same series as expected).

So the MOF crystallography method lives, although I've still yet to hear of it giving a structure with a nitrogen-containing compound (which rather limits its use in drug discovery work, as you might imagine).

Comments (10) + TrackBacks (0) | Category: Chemical News


1. FX on March 7, 2014 10:59 AM writes...

(For a bit of background, my own speciality is in the understanding of confined fluids and how confinement affects the fluid. Part of my recent work is on MOFs.)

It's been widely established that confinement into spaces of molecular dimensions (zeolites, MOFs, you name it) induces drastic changes in a fluid's structural, dynamical and even electronic properties. So, even if I like the idea of “molecular sponge” crystallography, how can they assess that confinement did not affect the molecular conformation? (To say nothing of reactivity/chemisorption between the MOF and the guest, which is another issue altogether, and might be at play in nitrogen-rich compounds for example.)

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2. organometallica on March 7, 2014 11:09 AM writes...

Oh! I'm shocked that I forgot about this when we were talking the other day. I'm really happy to see this repeated and desperately want to try it for my compounds! Let's see, do you think a metal phosphine complex will soak into the MOF?

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3. Rhenium on March 7, 2014 11:34 AM writes...

How amusing. I saw this on the Baran blog perhaps two days ago and sent an email to one of the authors expressing my delight. Now it turns up here!

Based on my reading of the supplementary material I understand that the structural solution is still quite challenging due to solvent inclusion and disorder.

I should point out that the Fujita group has a Nature Protocols paper from January 2014, that details their method much more clearly.

#5) The pores are relatively small, they might fit a small organometallic, say Fe(CO)x, but I think PPh3 might be a bit of a stretch. Perhaps a very compact silver carbene might fit?

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4. Haftime on March 7, 2014 12:42 PM writes...

Pore size is not going to be the problem for adsorption in MOFs - GFP has been adsorbed in one of Yaghi/Stoddart's bigger beasts - the real problem is going to be binding sufficiently strongly to avoid disorder. This raises the questions that FX asked - is the structure representative? I guess it's true to say that no crystal structure is truly representative of what is most interesting for most organic and organometallic synthetic chemists, but the unusual confinement and strong binding might exacerbate this problem.
I imagine organometallics will be particularly tricky because soaking a reactive complex with a strongly binding ligand could cause the complex to substitute into the MOF (this has been used synthetically), as FX hinted.

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5. Derek Lowe on March 7, 2014 1:08 PM writes...

For small molecules, I'm not so worried about the conformational information - I think that just compound ID and gross structure will be a boon. As for proteins, I think the thing to do would be to run a number of them whose structures are already determined by other methods, and compare. One can already have doubts (as pointed out by Haftime, #4), under any crystallographic conditions, so we'll have to see where these fit in, once (or if) anyone gets a protein structure by this method.

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6. Quintus on March 7, 2014 1:56 PM writes...

I like this method for X-ray structures.
Can anyone explain why there has not been a structure reported containing nitrogen? Is there a problem here, or is it that it simply hasn't been reported yet?

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7. Colonel Boris on March 8, 2014 12:55 AM writes...

A nitrogen-containing species shouldn't be a problem as such as a lot of the MOFs I've worked with have pyridyl or dimethylammonium groups in the pores. I guess it's a case of choosing the right MOF architecture for what you're hoping to trap.
Not all MOFs require high-temperature synthesis in DMF, so there's always the chance of species inclusion at the synthesis stage, in addition to post-synthetic absorption.

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8. Anonymous on March 11, 2014 9:02 AM writes...

Speaking from personal experience as someone currently trying to replicate this work, it is possible to use nitrogen containing compounds. I have used and diffracted successfully several simple anilines in my test rounds while getting used to the technique.

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9. Canageek on March 11, 2014 6:09 PM writes...

Wasn't there talk of a Nature Methods paper? Did that ever come out?

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10. Hap on March 12, 2014 9:03 AM writes...

Yes it was (from the Fujita group website):

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