Post Tagged with: "Derek Lowe"

Hot news on an old story

Some stories never seem to end. The hexacyclinol story is one of them. Is it over now?

I assume most readers will be familiar with the controversy about the two proposed structures of hexacyclinol, the original one (1) and a revised one (2), and about a total synthesis of 1 by James LaClair that was challenged by Rychnovsky and Porco on the basis of calculations and a synthesis of 2. The debate has been extensively covered in the blogosphere, e.g. in C&EN and by Derek Lowe.

Proposed structures of hexacyclinol

Proposed structures of hexacyclinol

There is some new evidence now. An Italian group have simulated the 1H and 13C NMR spectra of both structures using DFT calculations (Org. Lett. ASAP). The calculated spectra seem to point to 2 as the correct structure. In addition, 1 cannot have the same spectra as 2 according to the calculations. The authors summarize: “The structure of hexacyclinol is confirmed to be 2. Furthermore, if 1 had been synthesized or was formed from an unforeseen reaction, its NMR spectra are sufficiently different from those of 2 as to guarantee their distinction.” This seems to exclude LaClair’s claim that structure 1, which is the target of his total synthesis, happens to have the same spectral data as 2. The authors of the paper are of course reluctant to draw the obvious conclusion.

Update: This piece of news has been covered in Derek Lowe’s blog. There has been quite a discussion, with James LaClair participating in person! It has also appeared in The Chem Blog.

By February 13, 2009 4 comments synthetic chemistry

tert-Butyllithium Claims Fellow Chemist at UCLA

butyllithium

Story is from UCLA Newsroom (Jan 19th):

A UCLA research assistant who was seriously burned in a laboratory fire last month has died of her injuries.

The 22-year-old woman, whose name has not been released, died on Jan. 16 at Grossman Burn Center in Sherman Oaks. She was transferred there after initial treatment for second- and third-degree burns at Ronald Reagan UCLA Medical Center.

The accident occurred Dec. 29 while the assistant was working with T-Butyl lithium, a highly flammable compound, in UCLA’s Molecular Sciences Building. The fire was extinguished by a colleague.

The fire is under investigation by UCLA’s Environment, Health and Safety department.

Link to article: Research assistant dies of injuries suffered in December lab fire

Update 1: More experimental details are coming out.

A 23 year old female research associate/laboratory technician intended to add an (unknown) aliquot of 1.6 M t-bu-Li (in pentane) to a round bottom flask, placed in a dry ice/acetone bath. She had been employed in the lab for about 3 months. The incident occurred on Dec. 29, during the UCLA holiday shutdown between Christmas and New Years. Researchers are granted permission to work during the shut down for “critical research needs.” There were two post doctoral researchers working in the lab and the adjacent lab, with limited English proficiency.

The principal investigator had trained the employee to slightly pressurize the bottle (an ~ 250 ml Aldrich Sure Seal container) with Argon and withdraw the desired aliquot using a 60 ml syringe, fitted with a 20 gauge needle. The PI likes to use these particular syringes because they have a tight seal. There is no evidence that the employee used this method. Speculation: she may have just tried to pull up the aliquot in the syringe. Somehow, the syringe plunger popped out or was pulled out of the syringe barrel, splashing the employee with t-bu-Li and pentane. The mixture caught fire, upon contact with air. She was wearing nitrile gloves, safety glasses and synthetic sweater. She was not wearing a lab coat. The fire ignited the gloves and the sweater.

Six feet from the fume hood was an emergency shower. When the employee’s gloves and clothing caught fire, she ran from the area away from the shower. One of the post-docs used his lab coat to smother the flames. 911 was called. UCLA Fire Dept. and emergency medical, Los Angeles City Fire, and Los Angeles County Haz Mat. The EMTs put the employee in the safety shower for gross decon and then transported her to the ER. She’s currently in the Grossman burn unit in Sherman Oaks with second degree burns on her arms and third degree burns on her hands, a total of about 40% of her body. There was very little damage to the lab. Bill has not interviewed the employee.

From: http://list.uvm.edu/cgi-bin/wa?A2=ind0901&L=DCHAS-L&P=13210

Update 2: From Daily Bruin (Jan 14th): Lab safety to be revised

Update 3: For those interested, the Chemistry Reddit is also tracking this story: A death in the science family. Be carefull with tert-butyl lithium!

Update 4: Proper Aldrich Sure-Seal technique can be found here: Handling air-sensitive reagents

Update 5: Name has been released from the Daily Bruin (Jan 21st): Assistant dies of fire injuries.

Update 6: Jyllian Kemsley from C&EN has picked up the story (Jan 22nd): Researcher Dies After Lab Fire

Update 7: Sheri Sangji facebook memorial for friends and family (Jan 22nd):
http://www.facebook.com/group.php?gid=116158190606

Update 8: Derek Lowe reminiscing on fires with tertiary butyllithium (Mar 2007): How Not to Do It

Update 9: Rebecca Trager also covering the story for RSC’s Chemistry World (Jan 23rd): UCLA lab assistant dies

Update 10: Derek Lowe mentions new fatality from trimethylsilyl diazomethane (Jan 23rd): The Real Hazards of the Lab

Update 11: Critiques of lab safety in Academia: Lab safety and chemical hygene in acadamia blows[TCB], A Death in the Lab[MCC]

Update 12: I was cleaning up some of the rabble-debate whether to release the PI name and accidentally deleted more comments then was my intention. Apologies to all commenteers effected. (Feb 19th)

Update 13: C&EN releases PI name. Insights: Learning From Mistakes (Subscription needed, Feb. 23rd)

Update 14: Los Angeles Times investigatory story on the accident. Deadly UCLA lab fire leaves haunting questions (Mar 1st)

Update 15: ChemJobber: What happened to Sheri Sangji? (Feb 27)

Update 16: LA Times: New details emerge in fatal UCLA lab fire (Apr 29)

Update 17: LA Times: State fines UCLA in fatal lab fire Fined $31,875 and Cal/OSHA will prepare an additional report to present to the Los Angeles County district attorney for consideration of criminal prosecution. (May 5th)

Update 18: ChemJobber: Patrick Harran, peeing in the jury pool? (May 5th)

Update 19: Statement of Patrick Harran

My students and I deeply mourn the death of our friend Sheri Sangji, and we realize our pain cannot possibly compare with the anguish felt by her family. She was an exceptionally gifted young woman with a bright future ahead, and her loss is truly tragic.

Since Sheri’s death, attention has focused on inspection and training records. These protocols are very important in developing and documenting a culture of safety, but in this case they are largely unrelated to the accident of Dec. 29, 2008. Sheri was an experienced chemist and published researcher who exuded confidence and had performed this experiment before in my lab. Sheri had previous experience handling pyrophorics, chemicals that burn upon exposure to air, even before she arrived at UCLA. Her most recent position prior to joining the group involved “scale-up process safety.” However, it seems evident, based on mistakes investigators tell us were made that day, I underestimated her understanding of the care necessary when working with such materials.

Sheri’s death resulted from a tragic accident. The California Division of Occupational Safety and Health has found no willful violations in its report. Throughout my career, I have strived to create a culture of safety. I am haunted by memories of this tragedy and wish that nothing like it happens again – in my lab or any other. In continuing our research, I go forward with a heavy heart in remembrance of Sheri and with a rededication to safety. I will also work tirelessly to achieve Chancellor Block’s goal of making UCLA the leader in safe laboratory practices.

(May ~5th)

Update 20: Chemical and Engineering News: UCLA Fined In Researcher’s Death (May 5th)

Update 21: Chemical and Engineering News: Negligence Caused UCLA Death (May 7th)

Update 22: Harry Elston’s Recipe for disaster editorial in the Journal of Chemical Health and Safety 2009, 16 (3), 3. (DOI: 10.1016/j.jchas.2009.03.011) (March 29th 2009)

Update 23: Science: Taken for Granted: The Burning Question of Laboratory Safety (May 1st 2009)

Update 24: ChemJobber: If I were working with tert-butyllithium… (May 10th 2009)

Update 25: The Sheri Sangji Petition: A tragic & preventable death (May 12th 2009)

Update 26: The California Fatality Assessment and Control Evaluation (CA/FACE): Worker Fatality Alert (May ~14th 2009)

Update 27: A Tribute to Sheri Sangji: www.sherisangji.com (May ~15th 2009)

Update 28: C&EN: UCLA Appeals Citations by Jyllian Kemsley (June 17th 2009)

Update 29: LA Times: Family of UCLA lab fire victim criticizes investigation (June 22nd 2009)

Update 30: LA Times: Cal/OSHA chief to oversee criminal investigation of fatal UCLA lab fire (June 30th 2009)

Update 32: An intensely detailed account of the experiment that caused Sangji her life. C&EN — Learning From UCLA (August 3rd 2009)

Update 33: ChemJobber and Chemical Space

Update 34: C&ENtral Science — Evaluating Safety (August 3rd 2009)

Update 35: C&ENtral Science — Personal Protection from Fire (August 4th 2009)

Update 36: C&ENtral Science reports their timeline of the accident and allegations of tampering — Tampering with Evidence? (August 5th 2009)

  • The fire occurred shortly before 3 PM on Dec. 29, 2008. Sheharbano (Sheri) Sangji was taken to the emergency room and Harran followed.
  • After Sangji and Harran left, Los Angeles County hazardous materials crews cleaned up the lab. (Recall that medical personnel had put Sangji under the safety shower. Showers are supposed to run at a minimum of 75.7 L/minute for 15 minutes, so there should have been about 1,100 L of water to test and mop up.)
  • Harran returned to the lab around 7 PM and was asked by fire officials to shut down the experiment to ensure the hood was safe.
  • Sometime after Harran shut down the experiment, UCLA deputy fire marshal Christopher Lutton took photographs of the lab and Sangji’s hood. Lutton also told Harran that the lab would be locked and investigated, although there’s no record of exactly what Lutton said.
  • At around 7:30 PM, Lutton left the lab and went down to his vehicle remove his gear, call the locksmith, and call one of his colleagues.
  • At about 8:30 PM, Lutton returned to the lab to find Harran and postdocs Weifeng Chen and Hui Ding in the lab. In a later interview with Gene Gorostiza, the UCLA police detective who investigated the scene tampering allegations, Ding said that he and Chen removed six empty flammable liquids containers from the lab and put them in the building’s trash. They also put other solvent containers into a lab storage cabinet.
  • Lutton ordered everyone out of the room and stayed on the scene until the locksmith arrived at 9:55 PM.
  • The locksmith finished changing the locks at 11:35 PM. At that point, the doors were locked and Lutton took possession of the only key, put up yellow barrier tape, and left.
  • Lutton returned to the lab the next morning to find that the restraining bolts in a side panel to one of the doors had been released, allowing the door to open freely. Lutton told Gorostiza that at that point he discovered that the room contents had been tampered with. A timeline of the incident included in UCLA fire marshal documents says that, comparing photos of the lab taken in the morning to the ones taken the previous evening, containers of flammable liquids were removed, other containers were moved into a walk-in fume hood, a cabinet door was left ajar, and some items in the fume hood where the fire had occurred had been moved around.

Update 37: C&ENtral Science — Promoting Safe Research Practices (August 6th 2009)

Update 38: C&ENtral Science — Some Thoughts on Lab Incidents (August 7th 2009)

Mitch (Our best thoughts, from everyone at Chemistry Blog, go to her family at this time)

By January 20, 2009 103 comments Uncategorized

Diaza[12]annulene: Would You have Known Better?

The recent retraction of two papers regarding diaza[12]annulenes by Yamaguchi et al. and Shi et al. from separate groups have strengthened the argument for stronger peer review and more thorough literature review by authors. http://dx.doi.org/10.1002/anie.200704704

But anyone can be an armchair synthetic chemist and point fingers at what should have been done after the fact. The easiest finger to point, is presumably between 7 coauthors, 4 reviewers, 2 editors no one ran the appropriate literature searches to find that these reactions are known and yield products with exactly 1/2 the mass as those reported in the papers. But, now we come to the bitter truth in modern chemical research, we simply do not perform the thorough literature searches of yester’year. Some will say this is a problem, but assuming those 13 scientists are typical of scientists of today then it simply isn’t a fair commentary to make. So, I thought it would be more beneficial to reread the papers and see if I would have come to the same conclusions given the same series of data, as I’m oblivious to heterocyclic chemistry in general and the Zincke reaction in particular, and have a typically topical background like most chemistry graduate students (I’m a Nuclear Chemist after all).

First up the Yamaguchi paper: http://dx.doi.org/10.1021/ol061585q
The title is the One-Pot Synthesis of N-Substituted Diaza[12]annulenes. Just looking at the title, we should be expecting 1H,13C-NMR, definitely MS data, and likely a crystal structure since the molecule would have two cationic-like centers. Picture shown below.

As can be seen in the structure this monstrosity should have some serious pi-pi stacking possibilities, and isolating crystals shouldn’t have been too problematic, but none are isolated. An image of their NMR data for the structure above is below.

It would be at this point that the little voice in my head would be like, “hmm…. why do I have aromatic proton peaks? I should probably count those pesky buggers again. Yup, 12 delocalized electrons.” If one is postulating that this is antiaromatic, then one hallmark of antiaromatic hydrogens, located on the outside ring, are that they shift upfield (lower ppm) and lie to the right of 8 ppm and likely 7ppm. So, it would have been at that point where the paper would of confused me.

Second up the Shi paper: http://dx.doi.org/10.1002/anie.200702140
The title is the [12]Annulene Gemini Surfactants: Structure and Self-Assembly. So, we should be expecting yucky yellow oils, and with the word structure, perhaps even a crystal structure. The molecules examined are shown below.

Independently, they confirm the odd aromatic protons of Yamaguchi and they obtained a yellow powder, not necessarily an oil, but well within reasonable expectations. They did some calculations with Gaussian and discovered the results below.

The expected distorted structure is seen in II but lied 1.7 kcal/mol higher in energy than I. This is just odd, for a cyclic antiaromatic system we should expect to see 2nd order Jahn-Teller distortions shift the molecule away from planarity and this was not seen by calculations. This is where the authors and reviewers can be faulted, at that point some one should have suggested an experiment to see whether the NMR peaks would move upfield as a function of temperature. As scientists, we love making graphs, and that would have been a neat confirmation of both the structural predictions from calculations, and an easily verifiable hypothesis.

In summary, I don’t feel it is fair to fault the authors, reviewers, editors for not knowing every obscure heterocyclic named reaction. However, it is prudent upon all of us to ask the right questions about our research, to put-off deadlines if necessary, and to apply our full intellect and diligence to our experiments.

Some Armchair commentary here:

Mitch

By December 14, 2007 2 comments synthetic chemistry