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This Week On CENtral Science: Percy Julian, #sherisangji update and more

Tweet of the week:

Before we head to the network highlights, just a note that this overlord will be taking a spring break, so Grand CENtral will, too. And no, we are not headed to party central in Cancun with Beaker.

To the network:

Newscripts: Amusing News Aliquots and Tribute To A Numerical Inorganic Icon: Kenneth Wade

Terra Sigillata: Google Features Percy Julian, Legendary African-American Chemist and The Case Of The Malodorous Metabolite

The Chemical Notebook: Coke Committed To Plant Bottle Despite JBF’s Bio-based Ethylene Glycol Cancellation

The Safety Zone: People v Patrick Harran: Opposition to the appellate court petition and Chemical safety tidbits and papers, from OPRD

The Watch Glass: Birthdays abound: Percy Julian and Robert Burns Woodward, plus Liner laminate


Tribute To A Numerical Inorganic Icon: Kenneth Wade

University of Durham chemistry professor Kenneth Wade, famously known for the borane electron-counting rule that bears his name, passed away on March 16 at age 81. Chemists at the University of Nottingham, led by big-haired chemistry professor Martyn Poliakoff, have prepared a lovely video tribute to Professor Wade as part of their Periodic Table of Video series.

wadeChemists use electron-counting rules to determine bonding patterns in different classes of compounds, such as the familiar octet rule for first- and second-row elements, the 18-electron rule for transition metals, and the Hückel 4n + 2 rule for aromatic compounds. However, these rules don’t readily apply to electron-deficient molecules such as boranes that utilize multicentered bonding–a pair of electrons shared between more than two atoms–so other rules have been devised.

In 1971, building on the collective observations of other chemists, Wade formulated his n + 1 rule. Wade’s rule states that a cage molecule with a geometry based on a closed polyhedron constructed of triangles with n vertices will possess n + 1 skeletal bonding electron pairs.

Wade’s rule and its corollaries have been refined and extended by a number of researchers. When coupled with spectroscopic studies and theoretical calculations, these rules have been successful in showing the structural interconnections between boranes, carboranes, other heteroboranes, carbocations, organometallic complexes, and transition-metal cluster compounds.

Hats off to Professor Wade.


Google Features Percy Julian, Legendary African-American Chemist

What a fantastic surprise this morning on the 115th anniversary of Percy Julian’s birth:

 

Screenshot of Google search page on 11 April 2014 features chemist, Percy Julian. Credit: Google

Screenshot of Google Doodle on 11 April 2014 features chemist, Percy Julian. (Credit: Google)

 

I’m beside myself with joy to see this pioneering chemist be recognized by the most prominent search engine in the world.

I don’t know where to begin about Julian but I’m sure that many of you have seen The Forgotten Genius, the PBS-produced NOVA life story of the chemist. Julian suffered many indignities in his training, from being denied dormitory residence while earning his B.S. at DePauw University to progression to racial issues limiting him to a M.S. at Harvard. He later completed his Ph.D. work at the University of Vienna in 1931.

Julian is probably best known for using natural products as a template for making drugs. His first major feat, the synthesis of physostigmine, a cholinesterase inhibitor from the Calabar bean used to treat glaucoma has been recognized by ACS as a National Historic Chemical Landmark at DePauw University. This 11-step synthesis from phenacetin, the active metabolite of acetaminophen, was completed with his Vienna colleague, Josef Pikl, and students in the laboratory.

Julian synthesized cortisone, estrogen, progesterone, and testosterone from the Calabar bean compound, stigmasterol. Later, at Glidden Paint Company, a happy accident led Julian to find that soybean extract (soya oil) also contained the 17-member sterol nucleus, a much more accessible source. At this time, we had absolutely no treatments for rheumatoid arthritis. But cortisone, then made by Merck in a laborious 36-step synthesis, was found in 1949 to transform the treatment of rheumatoid arthritis. However, Merck’s starting material was deoxycholic acid from bovine bile. Julian’s synthetic work beginning with sigmasterol.

I could go on. So I strongly suggest that readers consult the ACS National Historic Chemical Landmark dedication and, please, watch The Forgotten Genius. You should buy the DVD, as I did for teaching in my pharmacology classes, but you can watch it in segments at the PBS NOVA page.


Amusing News Aliquots

Silly samplings from this week’s science news, compiled by Sophia Cai, Bethany Halford, and Jeff Huber.

This squirrel loves to horse around. Credit: Jim Zielinski/ZielinskiPhotography.com

This squirrel loves to horse around.
Credit: Jim Zielinski/ZielinskiPhotography.com

When is a squirrel not a squirrel? When it’s eating out of a squirrel feeder shaped like a horse, of course. [Washington Post]

Researchers get prairie voles soused and then study their “pairing behavior.” Anyone who’s been to a bar on a Saturday night knows how this study ends. [National Geographic]

“Shots, shots, shots, shots, shots – everybody!” Turns out, the teens who most enjoy listening to songs with alcohol-soaked lyrics are also most likely to drink and binge on alcohol. No word on whether training kids to emulate song lyrics can be traced back to Baby Mozart CDs. [NPR]

After being asked by a local radio station to name the ingredients in the chicken patty sandwich it serves students, Chicago Public Schools has responded by saying the sandwich consists of a “chicken patty” and “bun.” The evasive response has resulted in irate parents wanting to serve the school system plenty of knuckle sandwiches. [WBEZ]

Although Newscripts condones peeing in the ocean, researchers find that peeing in a swimming pool creates toxic byproducts. [Washington Post]

Oft overlooked elements get a little attention. Were you feeling taken for granted, Europium? [Mother Nature Network]

Have you checked out the Compound Interest blog? It’s pretty nifty. [Daily Mail]

Crank up that chemistry set. A $5 chemistry lab is in the making, inspired by wind-up music boxes. [C&EN]

According to researchers at the University of Louisville, three-dimensional printing may one day be used to construct a heart. The news is yet another example of the medical community putting the needs of tin woodmen ahead of the needs of scarecrows and cowardly lions. [San Francisco Chronicle]


People v Patrick Harran: Opposition to the appellate court petition

New arguments were filed this week in a California appellate court regarding the case against University of California, Los Angeles, chemistry professor Patrick Harran. Harran faces trial on four felony violations of the state labor code. The charges stem from the 2009 death of Sheharbano (Sheri) Sangji from injuries sustained in a fire in Harran’s lab.

One judge ruled nearly a year ago after a preliminary hearing that there was enough evidence to send Harran to trial. Last August, another judge ruled against defense motions to dismiss the case. Then, last October, Harran’s attorneys filed a “Petition for writ of mandate, prohibition, or other appropriate relief” with the California Court of Appeal.

To quote from a Safety Zone post on the petition:

The petition covers similar territory as the demurrer motion from last August: The defense argues that UC was the employer and Harran merely a supervisor. California Labor Code section 6425(a) makes it a crime for “Any employer and any employee having direction, management, control, or custody of any employment, place of employment, or of any other employee” to willfully violate an occupational safety or health standard in such a way that causes death or permanent or prolonged impairment of the body of an employee. Nevertheless, Harran’s attorneys write, the specific occupational safety and health regulations Harran is charged with violating reference either employer or no one at all (Title 8, sections 5191(f)(4), 3203(a)(6), 3383(a), and 3383(b)). Other regulations do call out supervisors. From the petition:

In the regulatory scheme, Cal/OSHA thus specifically identifies supervisors as the party legally responsible for certain acts when it deems necessary. In other circumstances, it simply prescribes duties of employers, and leaves to the employer how to divide responsibility for internal implementation of the safety standards. There is no principled justification to disregard the expressed policy preferences of the administrative body charged with promoting workplace safety in this state.

The two arguments filed this week were from the Los Angeles County District Attorney’s Office, in opposition to the petition. One, the “Opposition to request for judicial notice,” argues that the appellate court should not consider exhibits submitted by Harran’s team to support the petition. “The court may not consider outside facts on a demurrer, and may only consider questions of law relevant to the facial sufficiency of the pleadings,” the opposition document says.

The other argument filed this week is the “Opposition to petition for peremptory writ of mandate or prohibition.” This document first argues that Harran’s petition involves contested issues of fact that are properly addressed in a trial. It then goes on to argue that Harran was Sangji’s employer:

Harran stated to investigator Baudendistel that although Sangji’s payment was administered through the UCLA payroll department, the funds were from his research funds and “other funds that he controlled.” (Exh. 3, p. 91.) Sangji came to work for UCLA in response to an ad Harran placed. (Ibid.) Harran was responsible for the recruitment and hiring for his lab, and he conducted the job interviews. (Ibid.) According to Harran, it was he, not the UC, who was responsible for Sangji’s safety training because of her “classification by the University.” (Id. at p. 92.) Since Harran was in charge of the lab (id. at p. 90), presumably he controlled her day-to-day activities. The totality of these conditions seems to create a strong suspicion that Sangji was “any natural person in service” of Harran. (§ 3300, subd. (c); § 6304.) …

Under [the sponsored project] arrangement, Harran appears to administer an independent project with outside funding with support from the UC. Under this arrangement, he therefore shares employment responsibilities with the UC.

And regardless, he is liable as either an employer or supervisor:

In assigning criminal liability to supervisors, the Labor Code recognizes the basic truth that all companies must act through their employees. …

These examples show that the regulations do not establish a rigid scheme of employer duties, with the occasional imposition of a supervisory position. Rather, they should be given a common-sense reading in line with the reality of how firms operate. The more appropriate interpretation is that the regulations describe safety standards to be implemented by firms in a practical manner depending on their size and structure. As discussed ante, the Labor Code then becomes the relevant source of criminal or civil liability. It does not appear that the broad liability seemingly imposed by section 6425 is artificially limited by the regulations to only those instances where they impose specific duties on a “supervisor.” The more reasonable approach is to apply the plain meaning of section 6425 and impose criminal penalties on supervisory employees who have actually been given safety responsibilities by their employer, and who willfully violate those duties.

Replies to the opposition arguments are due to the court on April 30. Harran’s next status check with the trial court is on June 5, although the trial cannot proceed until the appellate court rules.

The Toronto Star recently published a long story on the case: A young lab worker, a professor and a deadly accident


Chemical safety tidbits and papers, from OPRD

A tweet from Chemjobber that Organic Process Research & Development editor Trevor Laird is retiring at the end of the year made me realize that I forgot to highlight OPRD’s annual “Safety of Chemical Processes” section at the end of last year. Making up for the omission:

Laird’s editorial: “There is a long way to go to educate and train to a high standard all chemists working in laboratories and chemical plants and to minimize the number of these incidents, which lead to damage to buildings and loss of profits, as well as loss of life. Companies always measure the cost of doing something (e.g., training) but never measure the cost of not doing something; there is a cost of not training staff, however, just as there is a cost associated with not complying with regulations (e.g., FDA regulations).”

Safety Notables: Information from the Literature, including notes about Togni’s reagent, dimethylsulfoxide, hydroxylamine, peroxides, dimethyldioxirane, nitro-explosives, and safer reagents for a number of reactions

Hydrazine and Aqueous Hydrazine Solutions: Evaluating Safety in Chemical Processes, from Lilly Research Laboratories

Safer Preparation of m-CPBA/DMF Solution in Pilot Plant, from Suzhou Novartis Pharma Technology

Process Safety Evaluation To Identify the Inherent Hazards of a Highly Exothermic Ritter Reaction Using Adiabatic and Isothermal Calorimeters, from Mylan Laboratories

Safe Scale-Up of a Hydrazine Condensation by the Addition of a Base, from AbbVie

Merck’s Reaction Review Policy: An Exercise in Process Safety, from Merck


Coke Committed To PlantBottle Despite JBF’s Bio-based Ethylene Glycol Cancellation

Here’s something that wasn’t very well publicized: JBF Industries has cancelled its project to build a bio-based ethylene glycol plant in Brazil.plantbottle-pkg

The company, and Indian polyethylene terephthalate producer, disclosed that it was putting the project “on hold” as part of its earnings back in August.

This is a far cry from the original announcement in September 2012, which took the form of a joint press release between JBF and Coca-Cola. JBF would have built a 500,000-metric-ton plant that would have derived ethylene glycol from cheap Brazilian ethanol. Coke would have used the glycol as part of its PlantBottle program, which incorporates bio-based glycol instead of synthetic glycol in the PET resins used in its soft drink bottles.

The Chemical Notebook learned about the JBF cancellation development at IHS’s recent Latin American Petrochemical Networking Meeting.  Otávio Carvalho, principal of the consulting group MaxiQuim, listed the cancellation in a presentation slide.

I asked Coca-Cola whether the cancellation had broader implications for the PlantBottle program. The company denied that it did. Coke blamed the cancelled project on “unexpected construction costs an a challenging economic environment”. The company said further that it is in discussions with other firms on a new glycol project. The talks may proceed for several months. Coke doesn’t expect such a plant to come onstream before 2016, which would amount to a delay of about a year versus JBF’s plans.

Coke also said that it is still working with Virent, Gevo, and Avantium, on a route to a bio-based alternative to terephthalic acid.

The JBF project always seemed like a stretch. This is an Indian PET company, albeit with a good track record of building projects overseas, constructing a glycol plant in Brazil, a bio-based glycol plant at that. Braskem, Oxiteno, or Dow would have seemed like more likely candidates. I suspect a few such firms did sniff out the project two years ago and decided that the setup Coke had in mind wouldn’t earn the cost of capital. (Actually, I know that one of the companies did exactly that at the time.)

 

 


The Case Of The Malodorous Metabolite

Over where I also write at Forbes.com, Matthew Herper, Senior Editor for Pharma and Healthcare, reported on GlaxoSmithKline’s NEJM clinical trial of darapladib in coronary artery disease. The drug had been developed as a small molecule, orally-formulated, subnanomolar inhibitor of lipoprotein-associated phospholipase A2.

Lp-PLA2 is associated with apolipoprotein B-containing lipoproteins, such as LDL and non-HDL particles, and is found in the necrotic center of atherosclerotic plaques. Formerly known as platlet-activating factor acetylhydrolase, the enzyme produces pro-apoptotic lysophosphatidylcholine and stimulates the synthesis and release of proinflammatory mediators such as IL-1 beta, IL-6, ICAM-1, and VCAM-1.

A meta-analysis of nearly 80,000 patients across 32 trials indicated that Lp-PLA2 was associated with a relative risk for coronary artery disease of 1.10 for each 1-standard deviation increase in activity, even when correcting for other influences. This magnitude of relative risk is similar to that for non-HDL cholesterol or systolic blood pressure.So, the enzyme seemed like a reasonable target for small-molecule inhibition.

Darapladib (SB-480848) emerged from screening for inhibitors and a synthesis campaign, each published in 2002 and 2003, and was selected for clinical trials. A study with 330 patients with coronary artery disease, The Integrated Biomarkers and Imaging Study-2 trial, showed that 12 months of darapladib (160 mg daily, p.o.) decreased the progression of atherosclerotic plaques that occurred in the placebo group, even when they were also receiving standard-of-care statin therapy.

Darapladib (SB-480848; N-[2-(diethylamino)ethyl]-2-(2-{[(4fluorophenyl)methyl]thio}-4-oxo-4,5,6,7-tetrahydro-1 H-cyclopenta[d]pyrimidin-1-yl)-N-{[4’-(trifluoromethyl)-4-biphenylyl]methyl}acetamide

Darapladib (SB-480848; N-[2-(diethylamino)ethyl]-2-(2-{[(4fluorophenyl)methyl]thio}-4-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[d]pyrimidin-1-yl)-N-{[4’-(trifluoromethyl)-4-biphenylyl]methyl}acetamide

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