Archive for the ‘Organic’ Category

Some Very Peculiar NMR Spectra in Organic Letters

Monday, August 19th, 2013

A close examination of the Supporting Information attached to this paper from 2011 in Organic Letters reveals some pretty interesting NMR spectra:

compound_5d_hnmr_zoom

(compound 5dfull spectrum)

Hmmmmm. I have collected hundreds of NMR spectra, and I can’t ever recall seeing a spectrum in which intensity was not a reasonably continuous function of chemical shift. That is, values of chemical shifts had only one associated intensity each, and no spectra had missing chunks of signal.

Here are some other interesting pieces of spectra from the same paper:

compound3j_hnmr_zoom(compound 3jfull 1H NMR spectrum)

 

compound3j_cnmr_zoom(compound 3jfull 13C NMR spectrum)

 

compound_7c_zoom  (compound 7cfull spectrum)

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You can check out all of the spectra in the SI for yourself—the file is open access.

So, what is going on here? One explanation is that we’re seeing something very scientifically interesting. I hope this is the case. Another explanation could be user error, or a malfunction on the part of the instrument and/or software used to collect and analyze the data.

Yet another explanation could be that unexpected or undesired peaks (e.g., those corresponding to impurities in the samples) have been erased from the spectra. Some of you might think this suggestion is outlandish—why would a chemical researcher manipulate spectral data in this regard?—but I cannot take credit for conceiving of this idea. I believe the first time I was alerted to this (highly unethical) practice was by the Editor-in-Chief of the journal in which this work appears.

Organic chemists and readers of this blog will recall that earlier this summer, Amos B. Smith III—the Editor-in-Chief of Organic Letters—penned an editorial documenting that he hired a data analyst to examine spectra and other data submitted to the journal for possible manipulation. The editorial included the statement:

I write to alert the organic chemistry community to a serious problem related to the integrity of data being submitted for review and publication by Organic Letters and to outline steps that the Journal is taking to address this concern. Recently, with the addition of a Data Analyst to our staff, Organic Letters has begun checking the submitted Supporting Information more closely. As a result of this increased scrutiny, we have discovered several instances where reported spectra had been edited to remove evidence of impurities. Such acts of data manipulation are unacceptable. Even if the experimental yields and conclusions of a study are not affected, ANY manipulation of research data casts doubts on the overall integrity and validity of the work reported.

I wish to reiterate that I have no definitive idea of what happened in the production of the spectra in this paper; this post only notes that they don’t look normal. In an effort to ascertain more about the spectra, five days ago, I reached out by e-mail to the first author, corresponding author, and Editor-in-Chief of the journal.

Dr. Bruno Anxionnat, the first author of the paper, did not respond. His former PI and the corresponding author on the paper, Professor Janine Cossy, replied with the following statement:

Dear Professor Bracker

There is probably a mistake as I know that the 1st supporting information with some spectra were wrong and I asked an other student to reproduce the experiments and sent back an other SI with the right spectra, may be the 1st SI was not changed by the right one.

Right now, I am abroad and can not check but I am going to check with the Organic Letters editorial office and I will tell theñm to contact you

Sincerely yours
Janine Cossy

I will note that Professor Cossy is an Associate Editor of the journal in addition to being corresponding author on the paper. You may recall that Smith’s editorial in Org. Lett. addressed the responsibilities of corresponding authors quite clearly:

In some of the cases that we have investigated further, the Corresponding Author asserted that a student had edited the spectra without the Corresponding Author’s knowledge. This is not an acceptable excuse! The Corresponding Author (who is typically also the research supervisor of the work performed) is ultimately responsible for warranting the integrity of the content of the submitted manuscript.

The responsibility to foster a research environment where all involved can confidently present their results, even if they are not optimal, resides with each research supervisor and Corresponding Author. At times, the inherent power of a research advisor’s position can create an atmosphere that leads some to embellish results.

In my e-mail to Professor Smith seeking comment, I made sure to mention his recent editorial. He sent back the following note:

Dear Bracher,

Thank you for bringing these discrepancies to my attention. As with any allegation concerning published articles, we have shared your concerns with the author, who is as you note an Associate Editor. Organic Letters has standard procedures for handling inquiries regarding the content reported in published articles, which are in play here.  As you may be aware, COPE (http://publicationethics.org/) provides  journal editors and publishers with guidelines for handling such issues.  Speculation and comment are premature at this time.

ACS and ACS Editors hold the conviction that the observance of high ethical standards is vital to  the entire scientific enterprise. Guidelines for a course of conduct by  those engaged in the publication of chemical research, specifically, editors, authors, and manuscript reviewers are set forth in ACS Ethical Guidelines to Publication of Chemical Research http://pubs.acs.org/userimages/ContentEditor/1218054468605/ethics.pdf.

Amos Smith

So, there you have it. The matter is being examined more closely, and it would appear the ball is in Organic Letters’ court. Interestingly, there are a few more papers (listing Anxionnat as first author and Cossy as corresponding author) where you might notice similar-looking spectra:

Anxionnat, B.; Pardo, D.G.; Ricci, G.; Cossy, J. Eur. J. Org. Chem. 2012, 4453–4456. (paper, SI)

Anxionnat, B.; Robert, B.; George, P.; Ricci, G.; Perrin, M.-A.; Pardo, D.G.; Janine Cossy. J. Org. Chem. 2012, 77, 6087–6099. (paper, SI)

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Go have a look and judge for yourself.

 

The OM Paper vs. Drinkel’s PhD Thesis

Friday, August 9th, 2013

ChemBark InvestigatesAs part of our investigation into the controversial paper published by Reto Dorta and coworkers in Organometallics, ChemBark contacted a source in Europe who was able to obtain a copy of the Ph.D. dissertation of the first-author of the paper, Dr. Emma Drinkel. Chapter 4 of the thesis carries the title “Synthesis, Structure and Catalytic Studies of Novel Palladium and Platinum Bissulfoxide Complexes”, and the chapter appears to describe the vast majority of the work reported in the publication in Organometallics.

The entire thesis is 174 pages long. ChemBark has made the editorial decision not to republish Drinkel’s thesis in its entirety, but rather, to provide a set of small excerpts that highlight important information, including a number of discrepancies with the paper in Organometallics. We are also republishing excerpts from the SI of the paper. I believe that this approach constitutes “fair use” with respect to copyright law, because (i) there is a time-sensitive need for the community to be informed about this important case, (ii) these excerpts represent a small fraction of the whole of the published works, and (iii) republication of these excerpts does essentially nothing to deprive Drinkel or ACS Publications of financial gain.

ChemBark’s excerpts from Chapter 4 of Emma Drinkel’s Ph.D. Thesis
ChemBark’s excerpts from the Supporting Information of the OM Paper

Drinkel’s thesis is dated “Zurich 2011”. In her curriculum vitae included at the end of the thesis, Drinkel reports her Ph.D. studies as having spanned “09.2007-09.2011”. Dr. Drinkel’s LinkedIn profile reports that she was at Zurich until December 2011, and she began work as a postdoc at Universidade Federal de Santa Catarina (Brazil) in July 2012. It is worth noting that the Organometallics paper was received by the journal on January 7, 2013—a full year after Drinkel departed from Zurich. This piece of information is interesting when one considers whether “just make up an elemental analysis” could mean “perform an elemental analysis” versus “fabricate the elemental analysis data”. Of course, the (arguably) ambiguous instruction could have been written many months prior to submission of the paper—while Drinkel was still in Zurich—or Drinkel could have carried all of her samples from Switzerland to Brazil.

A brief examination of the dissertation reveals that much of the information published in the supplementary file of the OM paper is identical to the information published in Chapter 4. This includes most of the characterization data and the prose used to describe the experiments. But a rapid comparison is hindered by what appears to be the root cause of the confusion between the main paper in OM and its corresponding supplemental file: Drinkel misnumbered some of the compounds in her thesis. The numbers in the discussion section of chapter 4 are shifted relative to the data reported for the same compounds in her experimental section. For example, compound 14 in the thesis’s experimental corresponds to compound 15 in Figure 13 from the thesis (pasted below). This compound is labeled 14 in Scheme 5 from the OM paper and 154 in the OM supporting information. The same problem goes for compound 16a/15a/15a/165a and others.

Figure 13 from the Thesis

Figure 13 from the Thesis

 

Scheme 5 from the Main Paper

Scheme 5 from the Main Paper

 

The numbering discrepancies in Drinkel’s thesis not only went unnoticed, they were exacerbated when the OM authors built their paper off of the chapter and decided to delete the label from compound 14 in Scheme 5. This is the compound associated with the now-infamous instruction to “just make up an elemental analysis”.

The written response from the editor-in-chief of Organometallics on the SI’s controversial statement regarding compound 14 included the following:

The author has explained to us that the statement pertains to a compound that was “downgraded” from something being isolated to a proposed intermediate. Hence, we have left the ASAP manuscript on the web for now. We are requiring that the author submit originals of the microanalysis data before putting the manuscript back in the print publication queue.

Indeed, there are no data for 14 written in the experimental section of Drinkel’s chapter 4—its preparation occurs as an intermediate in the preparation of 15 (using the numbering from Figure 13). With that said, the discussion section of chapter 4 mentions:

When 5a was treated with only 1 equivalent of AgBF4, unlike in the Pd case, the stable complex 14 was formed. No crystals could be grown to confirm the structure, but the 1H NMR spectrum of the complex shows the ligand is still symmetric. There is precedence for this type of chloro-bridged Pt dimers in the literature with phosphine ligands.

This statement from the thesis might appear to refute the claim in the letter that the authors could not isolate 14 and that it was simply a proposed intermediate, but the text of the main paper states that NMR was taken “in situ” after the first reaction. With that said, no NMR data are provided for compound 14 in the Supporting Information file, and an instruction is given to Emma (Drinkel) to insert these data. Perhaps the instruction to “insert” was given because the instructor already knew the data existed (based on what was written in the discussion section of the thesis)?

Beyond the problems associated with misnumbering, there are several discrepancies between the data reported in the thesis and the data reported in the SI of the Organometallics paper. All of the examples that I could find related to elemental analyses. Specifically:

SI-5b vs Thesis-5b

Compound 5b from the SI

Compound 5b from the SI

 

Compound 5b from the Thesis

Compound 5b from the Thesis

 

SI 11a vs Thesis 9a

Compound 11a from the SI

Compound 11a from the SI

 

Compound 9a from the Thesis

Compound 9a from the Thesis

 

SI 12 vs. Thesis 12

Compound 12 from the SI

Compound 12 from the SI

 

Compound 12 from the Thesis

Compound 12 from the Thesis

SI 165b vs. Thesis 15b

Compound 165b from the SI

Compound 165b from the SI

 

Compound 15b from the Thesis

Compound 15b from the Thesis

 

You can see that the authors chose to “count” different associated solvents when calculating the expected values for the elemental analyses, and they reported different observed results in the paper vs. the thesis for some compounds. Were these samples run multiple times? Since the original data have been demanded by the journal, I guess we’ll find out.

 

Stay tuned for continuing coverage…

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Note: In the reporting of this story, we wanted to give both the first author of the paper (Emma Drinkel) and the corresponding author (Reto Dorta) the chance to comment on the discrepancies we found in the data prior to the publication of this post. ChemBark first attempted to contact Professor Dorta by e-mail on Tuesday night (St. Louis time) and received no response. Dorta also has yet to respond to a second message, sent Thursday afternoon, that sought comment on the discrepancies reported in this story. A message seeking comment was also sent to Dr. Drinkel, at the same time, through her Facebook account. Should either author respond to our requests for comment, the responses will be posted in their entirety.

A Disturbing Note in a Recent SI File

Tuesday, August 6th, 2013

ChemBark InvestigatesA recently published ASAP article in the journal Organometallics is sure to raise some eyebrows in the chemical community. While the paper itself is a straightforward study of palladium and platinum bis-sulfoxide complexes, page 12 of the corresponding Supporting Information file contains what appears to be an editorial note that was inadvertently left in the published document:

Emma, please insert NMR data here! where are they? and for this compound, just make up an elemental analysis…

This statement goes beyond a simple embarrassing failure to properly edit the manuscript, as it appears the first author is being instructed to fabricate data. Elemental analyses would be very easy to fabricate, and long-time readers of this blog will recall how fake elemental analyses were pivotal to Bengu Sezen’s campaign of fraud in the work she published from 2002 to 2005 out of Dalibor Sames’ lab at Columbia.

The compound labeled 14 (an acac complex) in the main paper does not appear to correspond to compound 14 in the SI. In fact, the bridged-dichloride compound appears to be listed an as unlabeled intermediate in Scheme 5, which should raise more eyebrows. Did the authors unlist the compound in order to avoid having to provide robust characterization for it?

ChemBark is contacting the corresponding author for comment, and his response will be posted in full when we receive it.

This story points to very real concerns that young researchers can be instructed and pressured to fabricate data. Would a scientist be so concerned that a journal would reject his manuscript over a piece of missing characterization data that he’d feel pressure to make something up?

Expect more as this story develops…

Andrew Myers and Harvard Sued by Former PhD Student

Sunday, June 30th, 2013

ChemBark InvestigatesDr. Mark Charest, a chemistry PhD student who graduated from Harvard in 2004, is suing the university and Andrew Myers, his PhD advisor, over the royalties associated with a patent covering intellectual property developed during Charest’s graduate work.

In 2005, the Myers Lab published this paper in Science that described a new synthetic route to 6-deoxytetracycline antibiotics. Charest was the first author on the paper, and the work was patented by Harvard’s Office of Technology Development (prior to submission for publication). A company, Tetraphase Pharmaceuticals, was started to commercialize the work by licensing the tetracycline patent from the university.

According to Charest’s complaint:

  • Harvard’s policy is to distribute royalties equally among all of the inventors on a patent unless the inventors agree to a different distribution.
  • Harvard OTD asked Charest and his former labmates to voluntarily accept a distribution of 50% to Myers, 15% to Charest, 15% to Dionicio Siegel, 15% to Christian Lerner, and 5% to Jason Brubaker (the five co-authors of the paper).
  • The four co-authors besides Myers agreed amongst themselves to a distribution of 18.75% to Charest, 11.25% to Siegel, 10% to Lerner, and 10% to Brubaker. Myers would not participate in this discussion and his 50% share was not open to discussion.
  • When Charest later spoke to Myers, Myers told Charest to “tread lightly”, “be careful”, and “think about [his] career”. Charest interpreted these statements as threats.
  • Charest initially refused to accept an unequal distribution of the royalties, and then engaged in a series of exchanges where Harvard’s representative threatened to directly cut Charest’s share of the royalties or to shift the distribution of licensing payments to a second patent on which Charest was not listed as an inventor. Fearful of this threat, Charest signed an agreement to accept 18.75% of the royalties for the first patent (presumably, the distribution arranged by the four postdocs/students).
  • The second patent never materialized, and Charest believes it was a ruse fabricated to force his hand to volunteer to let Myers get a 50% cut of the royalties.
  • Later, Charest describes a second act in which Harvard’s OTD did shift royalties away from Charest’s patent.
  • Myers refused to serve as a reference when Charest applied for a position at a venture capital firm, and Myers would not return phone calls when a potential employer directly contacted Myers regarding Charest.

Charest appealed to an internal review board at Harvard, but his case was unsuccessful. His lawsuit filed on Friday seeks reallocation of the royalties, punitive damages, and a bunch of other stuff that is outside my complete comprehension. Read the document for yourself.

It will be interesting to see how this story plays out, but it would seem to be yet another cautionary tale that when you are a graduate student, you are in a position of incredible weakness. As is said, your advisor holds your paycheck in one hand and your letter of recommendation in the other. And in case you are naive, the chains don’t get unshackled just because you’ve graduated. You’re still going to need that letter of recommendation for future jobs, so if your old boss wants to take 50% of the royalties, what’s to stop him?

Nothing.

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Disclosure: I went to Harvard for my graduate work and regularly came into contact with Myers, Charest, and Brubaker, as my desk was right next to the Myers Lab. I know Mark Charest and had several conversations with him over the course of my graduate career. I think I saw him one or two times after he graduated, and I’ve had no interaction with him since I graduated from Harvard.

H/T to A.D. for tipping off ChemBark

Elsewhere: Universal Hub, Chemjobber (analysis of prof-student/postdoc fiduciary relationship), Chemistry Reddit, Chemical & Engineering News, In The Pipeline, The Harvard Crimson.

BRSM is Coming to America

Tuesday, May 28th, 2013

There’s a chemblog carnival afoot to wish BRSM well on his upcoming postdoc in the U.S. @JessTheChemist is curating the posts on her blog, here. You can check out more info on Twitter with the hashtag #BRSMBlogParty.

BRSM is a synthetic organic chemist with a great blog dedicated to the subject. I know little else about BRSM beyond that he/she is currently based in the UK. (Obviously, I’m not even 100% sure about his/her gender.) That makes answering some of the carnival questions harder, but I’ll give it a shot anyway:

1. What is your message for BRSM?

Best wishes for your upcoming postdoc in the US, wherever it may be and in whatever area of research.

2. What is one postdoc survival tip you would give to BRSM?

Try to be nice to—or at least respectful of—your colleagues. Be especially nice to people like janitors, security guards, secretaries, instrument staff, and administrators. There will be times where you’ll need their help getting out of a bind, and having any of these people as enemies can make your life hell.

3. Do you have a fun story you could share from your postdoc and/or US academic experience?

Well, there was the kitty job interview. There was also the time we (unknowingly) named our high-school science outreach program after a sexual act. Oops.

4. A survival tip for living in the US?

Relative to what you have in the UK, our public transportation is poor. If you are going to live in or near New York City, Boston, or San Francisco, you probably do not want a car—parking stinks. If you are going to live somewhere else, you probably do want a car.

5. What would you like to see on BRSM blog in the future?

Tasteful nude photos.

No, seriously, whatever you want. I would rather you keep blogging about what interests you than burn out blogging about what interests other people. And thanks for posting the Felkin-Ahn slides; I think they make a nice companion to Dave Evans’ Chem 206 notes.

6. Anything else?

Nope. Safe travels!

Quiz: Named Chemical Reagents and Catalysts

Sunday, May 26th, 2013

I made this little ditty on Sporcle. Given a systematic name of a molecule, provide the last name of the chemist for whom the reagent or catalyst is named…