36 Recently published DFT calculations by Giacomo Saielli and Alessandro Bagno in Organic Letters (DOI: 10.1021/ol900164a) have suggested the claim that LaClair’s purported synthesis of Hexacyclinol may be a hoax.
The evidence:
La Clair’s purported substance is the, erm, endoperoxide thingiee 1. The shifts, at least based on these high level calculations, aren’t even close. The conclusion: Some allege he may be untruthy in certain aspects of his professional work.
P.S. Here is a photo of the Xenobe Research Institute where Jim La Clair works:
At least they don’t have to go very far for tacos!
Back to top
mmmmmmmmmm tacos……..
Actually, that’s an Irish pub to the left. (You know a bar is good when folks are drinking beers at noon on Saturday.) But there’s a Mexican place to the right (not in picture — I’m sure you can get a taco there.)
The back of XRI is um, urban alleyish.
“That’s an Irish pub to the left”
That explains all the problems with the synthesis
You know, we should be able to get Google Street View for the Bionic Bros. in Berlin…
It’s not the sketchiness of XRI that’s the problem with La Clair’s AC paper – it’s the Bionic Brothers’ place (where there doesn’t appear to be facilities appropriate for a lab, no on-site NMR, etc.). How one would have done a multi(kilo)gram-scale synthesis there is unclear (and unlikely, probably).
Maybe the Scientology people have a related home base (though I would have figured they’d be more upscale). Maybe it was previously used by the people who neutered themselves for Hale-Bopp?
I don’t believe people will forgive JJLC – at this point, he’s like the Pete Rose of the chemistry world (minus the actual achievements and presumably the women friends in every National league city). Once Rose admitted he lied, people were pissed about that, and he was nuked anyway.
Is there discussion of the Bionic Bros. somewhere in the chemblogosphere? I remember folks making comments about the NMR thing, but I’d love to know if someone in Berlin ever made a trek.
I don’t know – I thought people made comments about the BB place on Dylan’s blog. Searching for it, I think someone had said that it had previously been used for video game makers (I had said that on In The Pipeline, and I’m pretty sure that a comment on Tenderbutton was the source). The on-site NMR thing I thought was from a note in the paper. DS’s comments on the BB were well liked. I don’t know if a local reader actually wandered over to the BB place.
Yeah, the last footnote (this last footnote BTW was added in proof) said that the NMRs were “determined by contract services” and were collected by N. Voss (Berlin).
Now that I have been in industry for a few months, I can say there are a lot of outfits who do not have NMRs on site but they are usually in Asia. (They do kilo work completely blind and then send you what they get out of it. I don’t guess they care if it is really what they say it is because by then they have your money.)
In the same note, it mentioned the operator “added the peak for CDCl3 to the spectrum of synthetic hexacyclinol” against the wishes of La Clair and then referenced it incorrectly.
Just bizarre.
Well, I guess we can use A-Rod as another test case for the Pete Rose phenomenon. Dude, high-stakes lies by people not well respected (or with lots of detractors) don’t end well – two thousand people with picks and shovels will inevitably unearth your bodies (and probably some other things you would have preferred stay unfound). Oh, and no one likes being lied to – finding out that you aren’t even worth a reasonably well-constructed and consistent lie isn’t going to make you feel warm and fuzzy, and if you happen to be a reporter with lots of sources, it isn’t going to be good for whoever did the lying.
I think people are sort of unreasonable at some level in the roid fiesta (we didn’t mind the ‘roids and their numbers while we could pretend they weren’t there, but we can’t actually deal with them once we know that they are and were), but lying to everyone in sight when they no longer trust you seems like dipping yourself in napalm and then starting a fire and roasting marshmallows at a propane tank farm. I guess that is one way to bring closure.
That kills me that Xenobe is next door to the Ould Sod. I had no idea that all the boozing I had done in North Park additionally offered a great wall to urinate on after the bar closed . . .
JJLC is in the house at In The Pipeline – he’s apparently unhappy with his criticism.
I can hear the violins from here.
I see he went for the ‘reframing as an ad hominem attack’ approach.
Derek was quite diplomatic, meanwhile… wonder if he’ll stop by here.
I would argue that this paper would have never been published had they chosen any molecule besides hexacylinol as a model. The paper makes poor effort to answer the question in the title. In fact, the calculations performed in the paper provide theoretical evidence against what we already know is experimentally possible. Similar but different molecules CAN have very similar NMR spectrum. We already know that we can calculate NMR spectra with a fair degree of accuracy. What qualified this paper to be an Org Lett article? I think that a fair amount of criticism is due to Saielli and Bagno for publishing weak research on the coat tails of controversy. By the by, the only true solution to this LaClair controversy is to synthesize his target molecule independently and publish the findings. Good luck getting funding for that.
I don’t think anyone but Dr. La Clair is looking for a solution at this point. Science has this pesky thing called data – because it is essentially impossible to refute a negative in most cases, people look for the burden of evidence. There isn’t a whole lot of evidence to support Dr. La Clair’s contention that his synthesis made hexacyclinol or the putative structure, since the NMRs have the funny solvent peaks (and someone on ITP noted, no solvent satellites or impurity peaks) that make them difficult to trust. In the absence of experimental data on the intermediates in the synthesis (which would have made this problem go away more than two years ago), the solution would be to take the paper as bogus, because no one is particularly interested in spending a few million to prove it so (or not).
Hexacyclinol is probably an easier test case for spectral simulation than lots of others, because the structures are polycyclic and so signals are likely to be highly interdependent and stereoschemistry-dependent. The paper shows what people can do with spectral simulation, and does it with a model system that should be reelatively easy. I don’t know if it’s worth an OL other than the controversy over hexacyclinol, but it does something useful anyway.
There have been many papers in recent times on computational calculation of NMR spectra that have helped to resolve problems with structure. Many of these have appeared in OL, JOC and JNP. Many of them have been the proof-of-principle variety. In any field, the earlier pioneering proof-of-principle papers usually get published in good journals. Once the method becomes accepted and established, then good journals would need something more substantial and relevant. If journals such as OL start demanding higher standards from such papers, it would only be a good sign indicating that they have accepted the method as an established one. On the other hand, enough number of interesting structural conundrums still lurk in the shadows to warrant such computational approaches and consequent publications in good journals.
On another note, one more reason why hexacyclinol is a relatively easy case is because it is conformationally rigid; a more flexible compound with averaged C13 NMR shifts would be harder to tackle because of the conformational dependence of the shifts.
My argument is that this is not proof-of-principle. The conclusion is based on the assumption (albeit a reasonable one) that the two molecules have different NMR data. However, we do not unequivocally know that the two molecules have different spectra. Its more like “support of principle” based on assumption. Most pioneering computational papers employ models that are known until that method is accepted. I think that this was a big leap, and it only got through because the model compound would generate reader interest.
Nothing in science is known unequivocally.
Mitch:
Yes it is. If I submit a proposal to NIH it gets trashed!
Does that actually count as science or as politics?
Yes it is. In the beginning God created the heaven and the earth in six days. An unequivocal scientific fact.
I disagree. Data is unequivocal(unless fraudulant), as are correlations. Interpretation of the data is where controversy arises. The IR spectrum of a molecule is just that. It says nothing definative about the structure of that molecule. Anything more than that requires accepting varying degrees of assumption depending on how far out on a limb you are willing to go. The credibility of scientific work has historically relied on being able to minimize the assumptions required to accept an interpretation of data. The paper in question could have minimized the amount of assumption required by comparing their data to the real data for an independently synthesized sample of La Clair’s target. This is an unlikely option. Another option would have been to at least compare to a subunit of the target. The peroxy ring would have been an excellent place to start. I think that more could have been done to make the paper more credible. I think they would have been called out on this had they chosen any other molecule.
By the way, does anyone know La Clair’s pedigree? I went to the XRI website thinking he might have a page, etc., but nothing….
I am not sure what his exact pedigree is, but I did work with him a few years back while interning at Dr. Michael Burkart’s lab at UCSD ( and no I am not one of the bionic brothers). I seemed to remember that he has an ivy league connection, either Columbia or Yale.
I think he worked with Gilbert Stork at Columbia at some point
Yes, he did graduate work at Columbia with Stork as did Rychnovsky. I wonder if these two have a beef from long ago???
2 things:
1) i learned from a german guy in my lab that bionic brothers used to be an rc car company that has since gone out of business and
2) his nmr spectra are completely ridiculous. no impurities, incorrect solvent peaks, and apparently no c-13. if you blow them up, you’ll notice that there are no c-13 satellites… meaning he worked with carbon not from this planet or he is completely full of shit (again)
subterfuge…
I have no beefs with anyone but am really getting sick and tired of this childish display of hate.
This site is going far further than discussing the scientific issues (albeit some of you focused on them). It is outright slanderous and shows a level of unprofessionalism that is simply put disgusting.
It is time that you stop slandering me and get back to work.
Please take this page down without further a due.
Jim La Clair
Thank you for the notice. I have softened the language. In the interim, I suggest you read the following article:
New York Times Co. v. Sullivan
On the advice of my attorney I will either remove the post or keep it up. We should know in the next few days.
You know, one would figure there were better things for you to do to legitimize your synthesis, starting with coming up with data and procedures for it (still waiting….), then to whine on blogs about being slandered and asking those who criticize you to shut up (or asking the blog owners to shutter criticism of you). That might have worked in 1970’s East Germany, but this isn’t the 1970’s and you’re in the wrong hemisphere.
Oh, and it’s “ado” (not “a due”). If you’re going to make threats, the least you could do is write them competently.
It’s also liable and not slander. But we’re just splitting hairs here.
My bad. Sorry.
On the advice of The Chem Blog’s legal staff, I have toned down the wording in the article but must remind you that I have, so far as I can, made every effort to provide you with the ability to defend yourself here on points of merit and fact and not made any claims about you that can be considered false or misleading by any measure as there exists an increasing body of work which establishes that your claims to have synthesized the molecule in question are, indeed, inaccurate or misleading.
Should you synthesize and prove my allegations incorrect I would be more than happy to be the first to apologize. If you have any data that you feel would establish the claims you make are true, please send them my way (kylefinchsigmate@gmail.com) and I will publish them as evidence that you are indeed not fabricating these matters of fact.
If the evidence you have is of a confidential nature, I would ask that you email me in a private communication about the nature of these facts (though I will not press you to send me the data) and I will, as soon as I read this, publish an immediate acknowledgment that I may have been wrong and the present supporting articles published in the aforementioned journals are factually incorrect.
However, as I do not believe such evidence exists (or could possibly exist on the basis of what I have read by others), I will keep this post in place – insisting that I am acting in good faith and have not made any libelous statements and that I stand by what I say as matters of fact established by rigorous scientific inquiry by multiple parties.
Thank you for understanding,
The Chem Blog
Well, you can have other hobbies outside of work. It’s not all or nothing. I’ve got a better idea genius. Why don’t YOU get back to work on re-synthesizing cyclohexanol. And stop threatening Kyle with fictitious legal crap.
Oh and by the way, it’s not hate. It’s just bemusement for now, but will depend on your behavior toward the blog author and commenters. Want to discuss a ’scientific issue’? Okay, how about the fact that your article is a case of ’scientific fraud’ in my expert ’scientific opinion’? I read the original in detail and looked at the spectra and also did some low level calculations on your proposed structure and I now present you with my expert ’scientific judgment’. You are guilty until proven innocent at this point.
Is that scientific enough? I am really angry that this article devalues Andjewandte, one of my favorite journals. So, I’m going to sue the crap out of you for hurting Andjewandte. My people will be in touch with your people shortly.
The World is full of adversities – those thorns strewn in ones path… Too bad that Dr. Voss added a chloroform solvent peak at 7.5 ppm but without the satelites.
Hell, Kyle: Take down this entire friggin’ blog! I demand it!
Oh, wait — no I don’t. But reverse psychology! Yes, I do. I demand it, without further a due!
I have nothing to contribute to the debate as I got to grad school and turned into a biologist, but having walked past that storefront many time in the last month, I would like to offer an observation. The building appears to be empty, but there are 6 or 8 blown-up copies of the first page of several publications hanging in the window on a variety of topics, but they all bear La Clair’s name.