science news

Alleged Data Manipulation in Nano Letters and ACS Nano from the Pease group

Leonard Pierce III

A recent paper from Rajasekhar Anumolu and Leonard F. Pease in Nano Letters entitled, “Chopstick Nanorods: Tuning the Angle between Pairs with High Yield“, had a collection of very interesting TEM images. Below are a set of images from both Figure 4E and 4F.

The images below show the boundary of one nanorod apparently overlapping the adjacent nanorod. This is not the only type of artifacts that are visible.

1 3 4
Adapted with permission from Nano Lett., Article ASAP (DOI: 10.1021/nl400959z). Copyright 2013 American Chemical Society.
In other parts of the same figure, nanorod boundaries seem to be obviously different colors than the surrounding background.

5 2
Adapted with permission from Nano Lett., Article ASAP (DOI: 10.1021/nl400959z). Copyright 2013 American Chemical Society.
Image manipulation does not seem confined to only this manuscript; in the supporting information of another paper in a different journal, this time in ACS Nano, entitled, Fabrication of Highly Uniform Nanoparticles from Recombinant Silk-Elastin-like Protein Polymers for Therapeutic Agent Delivery, Figure S2C looks to me to be manipulated. My eyes can find a grey square and a grey ellipse added to the image.

0
Adapted with permission from ACS Nano, 2011, 5 (7), pp 5374–5382 (DOI: 10.1021/nn103585f). Copyright 2011 American Chemical Society.
Both Professor Pease and Rajasekhar Anumolu were contacted two days prior to publishing this story for comment. Professor Pease informed me there was an investigation underway at the University of Utah into this matter and strongly encouraged me not to publish this story until the University completed its investigation. No comment was received from Rajasekhar Anumolu.

Prior to publishing this story Jeffrey R. Botkin, Associate Vice President for Research at University of Utah, contacted me confirming that “the University of Utah was informed of this matter by the editor of the journal and the University is conducting a thorough investigation for research misconduct.”

Update (8/15): Nano Lett paper is withdrawn.

Mitch

By August 13, 2013 85 comments science news

When is a Proton not a Proton?

A recent article in Accounts of Chemical research discusses this very topic as well as some other interesting facts revolving around protons, their structure and their generation. What does H+ signify? Well it means different things to different disciplines. If you are a physicist it refers to one of the fundamental elementary particles, if you are a chemist it refers to a hydrogen ion. So what is it exactly? Well it is a very strong acid about 1056 times stronger than 100% sulphuric acid! Its place in chemistry is well documented even although you can only add H+ to a molecule in the gas phase whereas only a solvated proton can be added in less gaseous media. This has great implications for biology especially where proton pumping is an important function, thus the structure H(H2O)+turns out to be a very important structure. This is especially so because the degree of solvation affects the rate of protonation particularly in proton/electron transfer.

According to Professor Reed, the author of this article a self – ionising acid, HA is very unlikely to form a H2A+ cation, the structure is better represented by the following equation:

proton

In the last few years it has emerged that the H+ is a 2-coordinate species, however, even this may extend to multi-coordinate when hydrogen bonding is involved. So what is the structure of H+ in water? This turns out to be a very difficult question to answer, and several instrumental methods have been applied to solve this problem, including IR and x-ray crystallography. These two methods and lots of hours have turned up H13O6+ ions as the structure. The experimental evidence backing up this claim can be found in this paper, which is open access!

Talking about protons leads to the strongest acids known H(CHB11Cl11) or H(CHB11F11), however the latter species is very difficult to obtain due to the ease with which it gives up its proton. These acids can easily protonate benzene or better alkanes! They are very useful in the study of protonation due to the complete inertness of the anions that do not undergo the usual corrosive reactions associated with other types of super acids. The acid H(CHB11F11) protonates butane to give the t-butyl cation at room temperature. Ethyl chloride is also protonated by H(CHB11Cl11) with concomitant loss of HCl to give the diethyl chloronium salts which can be isolated.

Oxatriquinanes are tricyclic analogues of the H3O+ ion. These very strong acids can H-bond to the last lone pair of oxatriquinane, which is a tetravalent oxygen species with a 2+ charge and is an analogue of the H4O2+ ion.

The Oxatriquinane oxonium cation.

ion

 

So if you are searching for a proton source not accompanied by the usual destructive counter ions try one of these carborane acids.

By August 8, 2013 6 comments science news

When Authors Forget to Fake an Elemental Analysis

Reto-Dorta

As first posted by ChemBark, a recent paper in Organometallics by Professor Reto Dorta at the University of Zurich is catching the ire of the online chemical community today [, ] for a quick throaway note left in the supporting information in the paper entitled, “Synthesis, Structure, and Catalytic Studies of Palladium and Platinum Bis-Sulfoxide Complexes“. On page 12 of the supporting information a note is left for the first author Emma E. Drinkel*, presumably by Reto Dorta, saying, “Emma, please insert NMR data here! where are they? and for this compound, just make up an elemental analysis…”.

Emma Drinkel Note

The full supporting information file is attached for your reference. Supporting information for: Synthesis, Structure and Catalytic Studies of Palladium and Platinum Bissulfoxide Complexes

Update 1: Letter from the Editor and Chief of Organometallics

gladysz

Wednesday 07 August
Dear Friends of Organometallics,

Chemical Abstracts alerted us to the statement you mention,which was overlooked during the peer review process, on Monday 05 August. At that time, the manuscript was pulled from the print publication queue. 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. Many readers have commented that the statement reflects poorly on the moral or ethical character of the author, but the broad “retribution” that some would seek is not our purview. As Editors, our “powers” are limited to appropriate precautionary measures involving future submissions by such authors to Organometallics, the details of which would be confidential (ACS Ethical Guidelines, http://pubs.acs.org/page/policy/ethics/index.html). Our decision to keep the supporting information on the web, at least for the time being, is one of transparency and honesty toward the chemical community. Other stakeholders can contemplate a fuller range of responses. Some unedited opinions from the community are available in the comments section of a blog posting: http://blog.chembark.com/2013/08/06/a-disturbing-note-in-a-recent-si-file/#comments

If you have any criticisms of the actions described above, please do not hesitate to share them with me. Thanks much for being a reader of Organometallics, and best wishes,

John Gladysz

Editor-­in­‐Chief

Update 2: Reto Dorta allegedly responds by email to Sufi.

reto-dorta2

Dear Sufi,

Thank you for your e-mail.

Compound 14 in the SI is an intermediate and has not been fully characterized, hence does not have a number in the manuscript. Wording and numbering of the compounds in the supporting information are wrong (on different levels!). Characterized compound 14 and 15a-c of the article correspond to compounds 154, 165a, 165b and 165c of the supporting info.

Anything else is being dealt with by the editors of the journal as we speak.

Best regards

Reto Dorta

Update 3: Carmen Drahl and Stephen K. Ritter report in C&EN:

blog-drahl

TL;DR Organometallics editor Gladysz told us that Dorta told him that the “just make up” statement was inappropriate. Also, the now-infamous SI was an earlier version uploaded to the journal servers at the point of submitting corrections. Reviewers saw another version.

Update 4: John Gladysz, Chief Editor of Organometallics, leaves a very detailed response on Paul’s blog.

john2

I have been meaning to contribute a post to this blog, where there has been so much good dialog involving the Reta Dorta manuscript on the ASAP site of Organometallics (om-2013-00067 or DOI: 10.1021/om4000067). There have been hits and misses, but I’d like to thank everyone for all input and commentary. Although I write this sentence with a wink to all my friends on my masthead page (http://pubs.acs.org/userimages/ContentEditor/1219929142245/orgnd7-masthead.pdf), this has made me muse whether an Editor-in-Chief could dispense with a high-maintenance Editorial Advisory Board and simply throw the various thorny issues that arise out for adjudication on a quality blog like Chembark.

I’ll attempt to address some of the many good points raised in a series of posts. I can’t promise I can reply to any counterpoints (e mail traffic has been heavy and will likely remain so), but I’ll be sure to read them.

A lot of comments have been made about the breakdown of the peer review process in this particular instance, and if you read to the end of this post you will get some specifics, within the confidentiality bounds that I am obliged to maintain as an Editor. However, you are going to have to bear through a general analysis of the many things that can go wrong with SI first.

The first vulnerability is in the initial submission. I don’t want to put down coauthor written manuscripts, but there are some corresponding authors who have clearly never laid an eye on their SI. Without this check, and I’m talking about a word-by-word read with attention given to every reagent quantity, spectroscopic data point, significant digit cutoff, etc., major errors are much more likely to slip through. My research group uses a proofing checklist, with every author fully participating, crystallographers excepted (except for their sections).

The second vulnerability is with the referees. I want to comment that I consider the pool of reviewers used by Organometallics as extremely conscientious. But obviously there will be cases, with any journal, where the SI is neglected.

A relevant digression involves JACS manuscripts. A reviewer may decide that the manuscript does not meet certain breadth/urgency criteria, and therefore not critique the SI. When such manuscripts are resubmitted to Organometallics (often with copies of the JACS reports), we do not render an Editorial decision until we are confident that the entire manuscript has been thoroughly peer reviewed.

The third vulnerability is with the Editors. I do not expect my Editors to carry out a word-by-word examination of the SI. However, we do follow an internal check list that I could in principle share, but all of the points therein can be found in our “Author Guidelines” (http://pubs.acs.org/paragonplus/submission/orgnd7/orgnd7_authguide.pdf)

An attendant vulnerability, pointed out by several on this string, involves the submission of the revised manuscript and accompanying SI. Suppose a reviewer or Editor requests that a melting point be added. At this stage, the Editor is unlikely to check anything other than the relevant paragraph. If an author has introduced other errors by some means (many comment about fixing minor typos), these will be overlooked.

In summary, it is necessary to look at error introduction from a number of perspectives, and it may be difficult for “younger” authors with less publishing experience to view things from the inside. I’ll eagerly “steal” any substantive additions that anyone offers if I ever have to present this analysis again, or incorporate it into a future Editor’s Page of Organometallics.

There are other things that can be done to reduce errors. When I did my major rewrite of the “Author Guidelines” that I inherited from my predecessor, I stole an idea from Dale Poulter at J. Org. Chem. and more or less required that all experimental data be reported in the main text of full papers. This excerpt is from section 4.3.8:

“For Articles and Notes, the bulk of the experimental section should be presented in the main text. Supporting Information should only be used to describe the syntheses and characterization of new compounds of subordinate interest: for example, the preparation of an isotopically labeled species by an otherwise known procedure or a salt with an alternative counteranion. Characterization data for known organic compounds prepared using a new catalyst would also be appropriate for Supporting Information.”

When om-2013-00067 was submitted, the experimental section (including all compound syntheses) was in the main text and the referees did exemplary jobs. One commented among other remarks “There is a fair amount of work in this paper, however 51 pages is definitely too much so downsizing the article would be appreciated especially as the relevance of the work is lost in the size of the article”. Neither the reviewer nor the processing Editor in his response recommended moving any content to SI. However, the author, in a not illogical attempt at accommodation, replied to reviewer 2 as follows: “We have shortened the article by taking away …. We have also incorporated all experimental data into the supporting information.” Exceptions are sometimes allowed to our policies, and in the processing Editor’s judgment it was more appropriate to honor the reviewer recommendation than adhere the protocol in section 4.3.8 of the Author Guidelines. Most Editors, including myself, would assume that a straight up cut/paste transfer between two documents could be competently carried out. However, this was not checked and nothing was returned to the referees, so the rest is history.

As noted above, additional posts may follow if time allows.

May your chemistry be highly successful, and may you execute it thoroughly and write it up in such a way that it can forever stand the test of time.

Best wishes,

John Gladysz
(on whose desk “the buck stops” for everything, good and bad, at Organometallics)
(for non-native speakers: http://en.wikipedia.org/wiki/Buck_passing)

Update 5: John Gladysz goes into extraordinary detail on what to do when a product is solvated [null]. Provides a handout: Solvates: Avoiding Common Errors

There has been due attention given to the microanalytical data in the Dorta manuscript and Drinkel thesis in this string.

Personally, the first thing first caught my attention was that both documents report identical reactant quantities, identical reaction conditions and workups, and identical product quantities and yields for the four compounds highlighted in the ChemBark post. However, the products are represented as solvated in the thesis, and unsolvated in the manuscript.

This of course cannot be, and is issue I want to focus on in this comment.

First, I’m a stickler for reporting both mass (typically g or mg) and molar (mol or mmol) quantities of all products (just as one does for reactants), not just the yields or yields and masses. I recognize that yields/masses only is a common format today, but this was not case some decades ago. Having the molar quantities greatly helps in checking the yield data, something I always do as a reviewer when solvates are claimed.

It is often the case that yields are incorrectly reported for solvates, and I made this mistake myself once (“Regiospecific and Stereospecific Reactions of Ph3C+ PF6– with Rhenium Alkyls (η-C5H5)Re(NO)(PPh3)(R); α vs ß Hydride Abstraction”, Kiel, W. A.; Lin, G.-Y.; Bodner, G. S.; Gladysz, J. A. J. Am. Chem. Soc. 1983, 105, 4958-4972. DOI: 10.1021/ja00353a020). Hence, ever since the mid-80s I have had a group handout on this topic with the example from the paper. The present version is on my research group website and pasted below:

Solvates: Avoiding Common Errors

I’ve never sent this out for external review, but this post is a step in that direction. Subject to input, it may eventually become an appendix in the author guidelines of Organometallics.

One point is that a solvated compound has a greater FORMULA weight than an unsolvated compound. This is the quantity that must be used in the yield calculation. The yield associated with a solvated product will always (for a given mass) be lower than that associated with an unsolvated product.

Another point is that the presence of solvate molecules must be independently verified, with NMR being the obvious choice, but there are other options. I’ll refer readers to the handout for this. I’ll also comment that hydrates are the most difficult types of solvates to treat quantitatively, sometimes there is no perfect slam-dunk solution for them.

Thus, with respect to the Dorta manuscript and Drinkel thesis, we will be focusing (apart from many other questions) on whether the reported procedures give solvated or unsolvated products (it cannot be both), and then whether the yields given are correct (we have done the calculations both ways, and also looked at the NMR spectra per the group handout).

Update 6 (8/16): Emma’s mother speaks up at Synthetic Remarks: In defense of Emma

Dear Dr Kieseritzky

I hope you don’t mind me contacting you, but I would just like to thank you for your comment on ChemBark. My name is Mary-Anne Drinkel, and I am mother of Emma. We are very proud of our daughter she has worked hard and conscientiously to earn her first class degree at Durham, her PhD at Zurich, and presently her Post doctorate work in Brazil- we know that fabricating data would be alien to her. I cannot believe that her good reputation, built up over these years can be destroyed in a week. I know nothing of the academic community, but the hostile and aggressive comments left on the blog sites are unbelievable. I don’t know if Reto Dorta was careless or has done a very bad thing, but I do know that Emma is the innocent party in this affair. How many PhD thesis could withstand the hostile scrutiny that Emma’s has been subjected to, with these bloggers determined to find evidence of wrongdoing – boasting about who broke the news first.

Emma’s husband has a new industry position in Switzerland, and they will be moving back to Europe very soon; this means Emma will be applying for jobs – she fears this affair will affect her chances, as she would be honest with prospective employers about her situation. They had decided to leave the academic world long before this episode because the competitiveness and political environment of university life was not for them. Emma is devastated that her good name at Durham and Zurich University will be forever tarnished by this affair.

My husband and I have felt so sad and so helpless as these events have developed – when I saw your comment that was sympathetic to Emma’s plight, it was the first bit of humanity I had witnessed in the whole affair, and I am grateful to you for that. Emma will get through this, she is resilient and has the support of her husband, family and friends – but we feel so angry that Emma has been subjected to this through no fault of her own.

Once again thank- you,

Best wishes,

Mary-Anne Drinkel

Mitch

By August 7, 2013 28 comments science news

Has Tamiflu got a cold?

Tamiflu, made by Roche and licensed by them from Gilead and stockpiled in many countries has proved to be a big money maker for Roche. It is one of two neuramidase inhibitors currently available for the treatment of influenza, the other being Zanamivir from Glaxo. Tamiflu is sold as its mono-phosphate salt. During the recent outbreak of avian flu due to the H5N1 virus Tamiflu was the drug treatment of choice for many physicians.

 

Now questions are being asked again about it’s effectiveness and it’s actual performance in clinical trials, the data of which has not been fully published by Roche in spite of promises to release this information. A new web site has been established to achieve the aim of providing doctors and patients’ access to this information. In a hard hitting editorial the editor of the British Medical Journal gives big Pharma a well deserved tongue (or in this case pencil) lashing, criticising the lack of information as to the clinical trial results of not just these two compounds but a number of others. Which she says must be made available to independent scrutiny.

It turns out that an review of the data on the available neuramidase inhibitors, commissioned by the British Government, discovered that around 60% of the data of the phase III trials collected by Roche has never been made available for examination.

Why does Big Pharma have a level of secrecy that would make the CIA look proud? Well I suppose in the first instance it’s about big money. One Tamiflu pill costs about $10, and that’s expensive. The recommended dosing regimen is 75 mg twice a day for 5 days, $100. Multiply that by the huge number of people contracting influenza and it comes to a lot of money. This year the sales are expected to DOUBLE from $350 million to around $750 million. So, I suppose that alone justifies the most of the secrecy concerning the reluctance to produce the complete trial results. Combined with a supply problem keeping the demand high also pushes the price up. I would hope that the deficit in supply is due to capacity problems and nothing else. Secondly; publishing the results of clinical trials give an insight into the companies working practices, which they most certainly don’t want made public. In the third instance if any minor complications turn up in the trials this may lead the company to tone down their significance, if there is any. Fourthly; could there be any bad publicity arising from any side effects of the compounds. No doubt there are perhaps other reasons that I am unaware of.

Moving back to chemistry the optimisation of the synthesis of Tamiflu makes a very interesting read and I recommend it as an excellent source of solutions to scale-up difficulties. It can be found here unfortunately behind a paywall. The synthesis starts off with shikimic acid and delivers Tamiflu in 17-22% yield after 15 steps. It has two azide reactions; the first one opens an epoxide to give a mixture of hydroxy azides 1 & 2 in a 9:1 mixture:

Both isomers form the same aziridine in the next step. The hydroxy azides are thermally labile, the stability being better in solution.

The next crucial step is the one pot sequence consisting of aziridine formation, via a Staudinger type process, using triphenylphosphine, followed by ring opening with sodium azide/sulphuric acid and finally acylation.

This series of reactions circumvents the unfavourable thermal properties of both the aziridine and the amino azide and allows for faster reactions and higher yields while maintaining process safety and quality of the product.

For this superb piece of process chemistry the Roche group received the Sandmeyer prize of the Swiss Chemical Society in 2006.

By February 16, 2013 3 comments science news, synthetic chemistry