The Incredibly Consistent R.B. Woodward

Fans of the blog know of my playful hero-worship of R.B. Woodward. A man so well-known for both his chemical triumphs and signature eccentricities (blue suits, cigarettes, slow lectures) should expect nothing less.

Recently, the ACS Division of Organic Chemistry gave me good reason to go goof around on their newly-designed site. I became especially intrigued with their collection of old National Organic Symposium brochures. Among male contemporaries, only E.J. Corey spoke at more NOS meetings (8) than RBW (tied with six others at 6 apiece).

Check out my slow-mo time-lapse photography, culled from appearances in the NOS brochures:

First, E.J. Corey, over a 52-year NOS span:

Next, RBW, over 28 years:

Wow. Same suit, same glasses, same haircut, same expression, far as I can tell!

(He really favored that left side, huh?)

Check out the titles of Woodward's talks:

• 1977 - "Recent Advances in the Chemistry of Natural Products"
• 1967 - "Recent Advances in the Chemistry of Natural Products"
• 1957 - "Recent Advances in the Chemistry of Natural Products"
• 1953 - "Recent Advances in the Chemistry of Natural Products"
• 1949 - "Recent Studies on the Structure of Natural Products"

(P.S. All of E.J.'s talk titles were completely different!)

Tiny Victories from Bloggy Activism

The chemblogosphere has certainly taken an activist turn in the past few years. Remember feeling the excitement of Paul's 2009 NaH oxidant live-blog? The ensuing four years saw chem blogs "cantrilling" space dinosaurs, uncovering IBX's secrets, investigating suspicious TEM images, and even weighing in on Nobel Prize selection. Heavy stuff!

Long-time readers understand that I've been in something of a self-imposed exile in the past few months, owing to a lengthy job search. But I couldn't resist writing about a mini-Christmas-miracle that arrived on 12/26. Seems that Dr. Brian Myers, the current ACS Division of Organic Chemistry webmaster, had acted upon my June post investigating the strange DOC logo:

"As a result of this posting, the ACS Organic Division has reverted to using the older version of the logo where the "D" is more prominent. It turns out the logo was "updated" in about 2007 while trying to make a high-resolution graphic for posters, NOS bags, and such. At that time, the leadership was unaware of the fact that the molecule was supposed to spell out DOC.  

As one senior DOC executive committee member recently wrote: 'I assumed it was a truncated steroid, which made historical sense. However it isn't because the ethyl and methyl aren't attached to the right places of what would be the CD rings.'"

Presto, Change-o!

Huzzah! The corrected logo now proudly adorns the DOC main page, and I even got a shout-out in their FAQs. I'm not gonna lie - I felt a small twinge of pride seeing this tiny change I helped effect.

But how did we get the logo in the first place?

Challenge: Dr Myers wants to know if anyone out there can remember the initial DOC logo designer:

"As far as I can tell, the first appearance of the logo was in 1985 on the NOS Program book; however, I would love to know the history of this including the name of the person who designed the original logo"

Anyone with insider info should leave a comment or email me at seearroh_AT_gmail. Let's put this chemistry "cold case" to bed!


A belated Merry Christmas to all, and hopes for a very Happy New Year
See Arr Oh

Friday Fun: Corporate Indicator? Refrigerator.

Here's a picture of our work fridge:

No, we didn't just clean it out; this is how it's looked all week. Amazing how little it's used when the company only employs a handful of people.

Gone are the niceties of early start-up life, the beer, the free soda, the fresh fruit and snacks. We don't even stock milk for coffee anymore. Note what's also missing: Forgotten lunches. Tupperware. Old birthday cake. Fast food leftovers.

That seltzer on the right? The boss's. Ditto the hard lemonade in the drawer. The Coke? The part-time facilities guy. I don't even know who owns the bruised fruit.

The champagne, however? That's mine. Relic of a more optimistic era - I was going to crack that when we won our first big contract.

Been sitting there for over a year.

Happy (?) Friday,
See Arr Oh

Highly Active, Barely Seen

Bench chemists know it's tough enough to control the multiple variables that go into any one reaction. But what about the ones you never saw coming?

The literature abounds with cautionary tales: Trace nickel (II) in the NHK reaction. Trace phosphate in the GFAJ "arsenic life" saga. "Metal-free" couplings found to rely upon parts-per-billion levels of Pd or Fe contaminants in "pure" sodium carbonate.

In yesterday's post, a volcanic mudpot-dwelling bacterium flourished in lab culture, but only when its growth media was doped with a rare earth element (REE). The authors had quite a bit of trouble eliminating residual metals from the growth media:

"When testing REE dependency (salts > 99% pure), it was observed that standard serum bottles resulted in a highly variable growth. . . Sand is one of the major raw materials of glass and may contain considerable amounts of REE, and Ce may be used as an additive during glass manufacturing. It was concluded that REEs in glass are extractable, at least partly, by the acidic media used."

Whoa! I confess, I've stirred hundreds of acidic solutions in glassware of all shapes and sizes, and never once have I assayed the rare earth content! And the glass wasn't the only cause for concern:

"Contact of the acidic medium with needles used for sampling was minimized as the metal seems to release REE as well. For these experiments, concentrations of trace elements were (in μM): NiCl2, 1; CoCl2, 1; Na2MoO4, 1; ZnSO4, 1; FeSO4, 5; and CuSO4, 10."

For those playing at home, some of these trace metals guest star at the ppm level in this media. Due to the materials used in glass and disposable needle manufacture, I guess there will always be a baseline of (potentially active) metal contaminants in acidic solution.

Want to take bets that one or more play roles in our favorite cross-coupling reactions?

Counterion Conundrum

(For Popkin's great Science News writeup, click here)
(Update - Also, Chemistry World!)

Update (11/13/13) - Blog buddy Lila Guterman of Science News has the inside scoop:
"An answer! Authors via @gabrielpopkin: cerium(III)chloride heptahydrate (99.9% pure) from Sigma (cat. nr. 228931-25G)"

~~

Fascinating news for the inorganic biochemistry fans out there: Scientists have ID'd a bacterium (Methylacidiphilum fumariolicum) living in highly acidic volcanic pools that seems to use rare earth metals in one of its enzymes. A multinational team modeled the enzyme with a variety of rare earth cores, and the bacterium appeared to selectively take them up in cell culture. Cool!

Just one small problem: What's the counterion?!?

My crack online reporting team has scoured the manuscript, finding only mentions of a mysterious Ce(III), along with triply-oxidized La* and Pr. Nowhere in the Supporting Information do they mention reagents used, and the reporter has confirmed that this subject wasn't broached.

Given the other salts the researchers added to the media, it's likely that they used either cerium (III) sulfate or cerium (III) chloride. However, Sigma-Aldrich sells no less than 10 different cerium (III) salts (Strem has over 20!), and I'm willing to bet they have markedly different bioavailability, oxidation potential, aqueous solubility...the works.

Readers, does anyone know what the cerium source is in this paper?** I certainly don't wish to draw unwarranted conclusions, but we're all still touchy over another recent dust-up having to do with a miraculous trace element.

Please let me know in the comments.

*IUPAC police: Throughout the paper, the authors refer to "Ln ions." Do you suppose they mean La (lanthanum)? Are elements abbreviated differently in other places?

**Interestingly, the authors note that their acidic growth media leached trace rare earths out of the glassware. I've never looked at that as a reaction contaminant, but I guess I'll have to start!

Start-up, Year Two

As my tiny company hovers on the brink of non-existence, I recently passed my second-year employment anniversary. Here's how the numbers shake out for 2013:

(Year One Stats)

Time
"Standard" 40-hour work weeks: 2
45-60 hour weeks: 46
60+ hour weeks: 4
Total hours where I've been the only employee in the facility: >300
Weekends worked: 4
Holiday + vacation + sick days used: 29
Paycheck snafus: 3

Chemistry
Total Reactions Run (2011-2013): >850
Synthesized compounds evaluated in disease models: 10
Total NMR Experiments (2011-2013): >1,150
Total Papers Downloaded (2011-2013): >2,200
Total Inventory Chemicals: 380
Fume Hood Failures: 3
Total boxes of gloves used (2011-2013): 23

People
Turnover (2011-2013): 70%
Company Interviewees: 7
Happy Hours: 1

Biz Dev
Grants Submitted: 12
Teleconferences: 63
Conferences / Events: 14
Slide Decks constructed: 36
Presentations: 5
Total Business Cards Distributed (2011-2013): 400+ 
Total Reimbursed Mileage (2011-2013): 3,100+

Ephemera
Total Purchase Orders (2011-2013): 317
Continuing Ed / Training Classes: 20 hours
Holiday Parties: 0

What's that 'Bright Orange' Chemical?

As reported by NPR this morning, the U.S. Supreme court hears the case of Carol Anne Bond, convicted of violating the Chemical Weapons Convention through her repeated attempts to poison her husband's mistress with two industrial chemicals. From NPR:

"Bond stole toxic chemicals from the chemical manufacturing company where she worked and ordered other chemicals over the Internet. She combined the chemicals into a compound that is potentially lethal in small amounts — and is also bright orange. Bond spread the toxic material on her rival's mail, mailbox, front doorknob, car door and other surfaces.

But because of the orange color, the mistress, Myrlinda Haynes, easily spotted the chemicals and avoided any injury except a thumb burn."

 I tried to look for information on the identity of this "bright orange" substance. Digging into the SCOTUS brief, it seems Ms. Bond purchased two chemicals:

". . .petitioner [Bond] decided to punish Haynes. She purchased some potassium

dichromate (a chemical commonly used in printing photographs) from Amazon.com, and stole a bottle of 10, 10-chloro-10-H-phenoxarsine (an arsenic-based chemical) from her employer. Petitioner knew the chemicals were irritants and believed that, if Haynes touched them, she would develop an uncomfortable rash."

According to this oral argument from 2011, Ms. Bond had been a microbiology technician with Rohm & Haas, from whom she nabbed the arsine compound. What I haven't been able to figure out from the stories or briefings is whether she intended the combination of two potentially poisonous, irritant substances to function apart, or to perform some sort of solid-phase oxidation to, for example, phenoxarsine oxide (a known antimicrobial compound).

This case needs more chemical context...paging Deborah Blum!

Cast a Wide Net

After Tuesday's post (covered graciously by Derek and Chemjobber), I received plenty of well-wishing and interesting emails pointing to potential jobs. I'm truly thankful for all of the kind responses.

One persistent question came up in multiple venues: What type of job was I looking for?
Was I, perhaps, being too picky?

Below, I've listed a smattering of the job titles I've applied to in the past three years. I'll let you be the judge(s):

Scientist I
Scientist II
Scientist III
Sr. Chemist
Project Leader
Principal Scientist
Blogger
Research Investigator
Investigator
Associate
Polymer Scientist
Consultant / Manager
Flavor Scientist
Technical Adviser
Patent Associate
Biochemist
Asst. Professor
Adjunct Professor
Educational Assistant
Tutor
Editor
Asst. Editor
Social Media Manager
Science Writer
Medical Writer
Lead Chemist
Business Development Associate
Business Development Manager
Marketing Rep
Sales Associate
Customer Affairs Rep
Organometallic Scientist
Accounts Manager
Business Analyst
Applications Development
Metallurgy Engineer
Research Chemist
Food Scientist / Engineer
Analyst
Team Leader
Asst. Director
Technician
Metabolism / Fate Scientist
Research Asst. Professor
Technology Transfer Specialist
Product Specialist

(more as I dig 'em up...)

Reconciliation

A few days ago, I made a sardonic comment on Twitter about the never-ending scientific job quest:

An odd thought: if major diseases aren't cured in my lifetime, it may be because my entire generation spent its time applying for jobs.
— See Arr Oh (@SeeArrOh) October 18, 2013

So, was I just being over-the-top? Let's do some math.

In the past 4 years, I've held 3 different jobs; I'm currently looking for Job #4.

Jobs Applied To, by cycle: 184, 43, 126 (so far!) = 353 jobs
@ 1 hour per job (discovery, cover letter, emails, recommendations, etc.) = 353 hours

Phone Interviews, by cycle: 13, 3, 10 (so far!) = 26 phone calls
(Just 15 minutes? In my experience, they last 45): 26 * 0.75 hour = 20 hours

On-Site Interviews, by cycle: 7, 2, 3 (so far!) = 12 on-sites
@ 8 hours per interview + avg. 4 hours travel = 144 hours

Miscellaneous: Job fairs, reformatting CV, career events, webinars, networking events, ACS meetings, cold-calls, personal development, continuing education = 100 hours

Grand Total: 617 hours spent on some aspect of job-hunting.

Let's put that number into perspective. 617 hours is 25.7 days. Not working days, mind you. Actual 24-hour days. Many U.S. companies start entry-level employees at 2 weeks' vacation, or 80 hours of earned time. That's 320 hours over 4 years.

I have spent nearly twice as long applying for jobs as I have taking vacation in the last 4 years.

(Bonus irony: Several of those vacation days were taken to attend on-site interviews.)

If we measure a "standard" industrial chemist working week at ~50 hours, then I've spent 12.3 working weeks looking for jobs. That's 3 weeks' time, annually.

How much science could you do with an extra 3 weeks? Or if you actually used your vacation to relax, as opposed to looking for work?

Final thought: I'll bet you good money that I'm underestimating the time I've spent searching.

Any leads? I'm willing to listen. Drop me a line, seearroh_AT_gmail

~ Still no new job. Resume radio silence ~

A Brief Interlude

No, I haven't found a new job yet. But, I wanted to take a brief respite from watching a small start-up company crumble all around me, in order to point you to this:

Credit: Randall Munroe | Science Magazine
(Here's the full comic)

Yes, that's the Randall behind xkcd, drawing an Open Access journals infographic in last week's special "Communicating Science" section in, well, Science (!!!). He now joins Jorge Cham (PhD Comics) in the pantheon of cartoonists-cum-science-communicators to grace its hallowed pages in the past few years. It perhaps does not surprise regular readers that I'm an ardent fan of both artists.

I figured that, given recent calls for greater public understanding of science, and even chatter of drawing total synthesis cartoons, these early sci-comic trailblazers should be widely recognized and praised for their efforts. I certainly enjoyed it!

[Back to the hunt...Resume radio silence]

Hiatus

My apologies to regular readers, but Just Like Cooking is going into radio silence while I look for jobs.

I must redouble my search effort, and something's gotta give.

If you have any helpful information, I'm willing to listen. seearroh_AT_gmail

Respectfully,
See Arr Oh

Summer flowers, 2013

A Tasty New Development

Hey there, readers! You may have seen the chatter this morning, or perhaps you've seen Carmen's or Andy Revkin's write-ups?

It's time to hear it from the dog's mouth: I'm now part of the Food Matters family over at Scientific American!

Now, this doesn't mean I'm closing up shop here at Just Like Cooking; far from it. Following Ash's example, I'll write about my love of food chemistry over there, and my love of [everything else] over here. Sound good?

Have a peek at Bora's intro post to learn more about all the new faces, and check out all the smart things my co-authors have written over the years.

Looking forward to this exciting new adventure. Thanks again to everyone who made it happen, and for all of you here at JLC for reading.

Stock Photo Science - Colchicine

Our tiny company doesn't have a true marketing or business development staff, so publicity often falls to the scientists - y'know, during our "down time." : )

For the past month, I've been trawling stock photo sites and "how-to" guides to assemble some company brochures for an upcoming event. Yesterday, I dug up this stock photo gem:

Source: iStockphoto

Now, Just Like Cooking 1.0 might have beleaguered the graphic artist, decrying his lack of experience and shouting about why we need more chemists in design departments. 

But I'm tryin', Ringo. I'm tryin' real hard to be the shepherd. Let's go piece by piece and try to figure out why we can't print this on our marketing materials.

For starters: the molecule I think they're looking for, colchicine, isn't exactly unknown. Doctors and healers have prescribed this plant extract for centuries to treat gout and local inflammation, despite concerns over its toxicity. Chemists have known how to make colchicine since at least the mid-1950s. 

So, here's how the molecule should look. There's some important differences here, perhaps most importantly that the acetamide (the "top" functional group, CH3-C=O-NH) should actually have a bond to the central ring. 

Next, let's move to the bottom right ring, which I'd call a cycloheptatrienone ("hepta" = 7, "trien" = 3 double bonds, "one" = ketone functional group). See how the double bonds are shuffled around in the stock photo? That would be OK, since the system does have other resonance structures, forms where just the electrons move around without breaking the carbon framework. But this structure, where the C=O and C=C bonds overlap, makes 5 bonds at that carbon. That only happens under very specific conditions, but certainly not in this drug.

Finally, check out those bonds on the left. We organic chemists use bond notation to infer a lot of crucial details, not least which atoms connect to which other atoms! Note the line drawn from the 6-membered ring to the "C" of the bottom methoxy (H3CO-) group. Perhaps an artistic choice, centering the group over the bond, but the real molecule shows a C-O bond. 

I know photographers don't often consult chemists before they take these shots, but I'd invite their input here. Wouldn't their business do better if their photos were accurate? 

Speaking as a scientist-cum-designer, it would make my job easier.

Happy Friday, everyone.

-SAO

Bruceollines: Short and Sweet

You can't put your finger on it, but sometimes you just feel compelled to read a paper. This one, from Org. Lett. ASAP, scratched all the usual itches: protecting-group free total synthesis (check), traditional medicine (check), tropical diseases (check), and cool off-the-shelf reagents (check).

I must admit, Gordon Gribble's name at the top caught my attention, but his co-authors hail from the University of the West Indies, a school I've always been curious about.*

The goal? Fast, selective production of bruceollines, medicinal compounds isolated from the roots of a Chinese shrub. The authors initially try to assemble the common indole (the 6-5 aromatic ring) core of the bruceolline family using Fischer conditions, but the starting materials have other ideas and form non-productive intermediates. Starting over, palladium catalysis proceeds smoothly, then relatively gentle oxidation (DDQ) produces the fully oxidized bruceolline E (see picture).

To access the final compound, Gribble & Co. must reduce just one of E's two ketones. The authors attempt borane reductions, but the "usual suspects" (CBS, Alpine) fail miserably. Optimization with (+)-DIP-Cl produces the final bruceolline J in high yield and ee. To make the unnatural enantiomer, the authors turn to a personal favorite: Baker's yeast, more commonly found in breads than labs. After 14 days in a warm, sweet slurry, the wee beasties return ent-bruceolline J in 98% ee.

The synthesis, only 4 short steps, should open the door to develop new antimalarial compounds.


*First, the Hawaii paradox - recruiting high-end, serious grad students to work 4-6 years in a tropical paradise. How does that work? And how do shipping delays from the mainland impact project selection? I can imagine that protecting group-free, relatively robust chemistry would have to be the norm, to survive storms, delays, humidity, etc.

WWWTP? C'mon, TIME Magazine!

Update, 18:00 GMT - TIME has removed the stock photo,  fixed the strange "Period Table" language, and appended a correction. Kudos to the editorial staff for fast turnaround.

You can't go anywhere on the Internet today without hearing the clamor surrounding newly-confirmed element 115. Fantastic achievement, and another stepping stone towards the long-predicted "island of stability" - super-heavy atoms rumored to have longer lifetimes and higher stability (somewhere north of 118).

But the reporting surrounding the feat? A little less excellent.

Take, for example, this snippet from TIME's Science & Space desk. It hits all the high points, culling quotes from Lund's press release and explaining in plain English how the element came to be. But there's two glaring errors in the first inch of column!

Source: Time.com

1. Where on Earth did that stock photo come from? And who vetted it? First, no one uses the term "Joliotium" for Element 105 anymore; that's been Dubnium since 1997. Even when Joliotium was in play, no one abbreviated it as "Ji" (they used Jl). And Rutherfordium (Rf) isn't 106, but 104. 106 honors Glenn Seaborg, and shortens to Sg.

2. I've never heard the Periodic Table called the "Period Table" before. Are we describing atoms and elements, or 18th-century furniture?

C'mon, TIME, you can do better than this!

On Jargon

While reading Gary Stix's interview with Breaking Bad scientific advisor Prof. Donna Nelson, I stumbled upon a very telling chunk of text (emphasis mine):

"...the reduction step [for methamphetamine production] can vary from one synthesis to another, and there's a lot of differences in the reducing agents. And so I said, I don't know what reagent you want. They said to send them a list, and they liked the one that was aluminum-mercury because it would be easier for the actors to say those words.

That's another example of where I let [the producers] be boss. I wouldn't go back to them and suggest another reagent because it might be safer, cheaper, or have a higher yield. I just said, 'yes, sir.'"

"Sodium cyanoborohydride? No way am I saying that!"
Credit: AMC

Food for thought, especially for those of us trying to package chemistry in a more palatable format for folks outside the lab. But, the more I scratched my head over this situation, the more I wondered...are reducing agents that tough to pronounce?

Over at xkcd, Randall Munroe cheekily trounced our current cultural fixation on trochees, spoken words with a two-syllable stressed / unstressed pattern (ninja, pizza, Wal-Mart, Ke$ha, Xbox, etc.). "Aluminum-mercury," though taken right from the periodic table, hardly rolls off the tongue: seven* syllables!

"Classic" reagents for the reaction in question, like sodium cyanoborohydride (10 syllables) or sodium tris-acetoxyborohydride (12) certainly won't get by the writers without a grumble. But what about formic acid (4, with two trochees)? Raney nickel (4, two trochees) should also pass muster. Even better, maybe you could just fold the first two reductants into the generic "borane" (2, trochee) category?

Hey, AMC: Let's do lunch.

*And, of course, 8 if you live in the UK, and add that extra "i" to aluminium!

Link Farm: Chemistry Communication

Blogs, like any medium, shift, change, and grow over time. At first, I devoted my humble corner of the internet to food chemistry. After a while, it became a tool to root out misconceptions about chemistry in popular culture.

Well, to borrow a phrase from Click and Clack, I've come around for the "third half of the show" - figuring out how to bridge the gap between the growing public desire for accessible, informative, entertaining science content and chemistry's approach to that communication. A lot of terms have swirled around this issue: "punching down," #BogusChem, "Inside Baseball," 'in-reach' not outreach, #chemophobia, and "dumbing down," to name just a few.

Thanks for the tip about the magnets, Andre!
(P.S. Yes, I know "D" isn't an element)

This post will serve as a (growing) collection of pieces dedicated to thoughtful chemistry outreach.
Readers: Have a favorite post I haven't included? Send it along in the comments.

Janet Stemwedel, Doing Good Science: "When we target chemophobia, are we punching down?"

Chad Jones, The Collapsed Wavefunction: "Punching down? I don't remember swinging at all."

Ash Jogalekar, The Curious Wavefunction: "Where's the chemistry lobby? On why we need a National Center for Chemical Education."

See Arr Oh, Just Like Cooking: "The Chemistry Popularity Conundrum"

Michelle Francl, Slate: "Don't Take Medical Advice from the NY Times Magazine"; Nature Chemistry: "How to counteract chemophobia";

Paul Bracher, ChemBark: "Combatting Chemophobia"

Rebecca Guenard, Atomic-O-Licious: "Chemistry Isn't Just About Chemicals"

Science 2.0: "Chemophobia - The Unnatural Fixation of Activists"

Chemjobber, Dr. Rubidium, See Arr Oh, Chemjobber: "Chemistry Avengers" (podcast)

Marc Leger, Atoms and Numbers: "Consider the audience when addressing chemophobia"

Chris Clarke, Pharyngula: "Did you know douchebags are full of dihydrogen monoxide?"

Andrew Bissette, Behind NMR Lines: "In defense of #chemophobia"

More to come...

Podcast: Calcium Redux

My post on calcium catalysis didn't really engage a wide audience of readers the way I had wanted it to. A few kind souls helped me refine my approach, which I thought might work better as a radio blurb.

Dear Jake: Thanks, I took on your challenge. Here's my new entry:

Music: Hall & Oates, Bird and the Bee

Readers, whaddaya think? More accessible, less? Please let me know in the comments!

Catching Copper's Ghosts

Copper, copper, everywhere (and much more than you'd think). It's found in coins, wiring, statues, paints, and even as part of a balanced diet. Chemists, in particular, have long loved copper for its ready availability, well-defined redox states, and its wealth of reactions; just last week, Prof. Sherry Chemler (SUNY-Buffalo) recounted nearly 100 years of copper's catalytic successes* in a Science perspective.

Source: Ogle / Bertz group | Angew. Chem.

Though scientists have long studied copper-catalyzed reaction, several short-lived, unstable intermediates
have defied characterization. Now, Profs. Craig Ogle and Steven Bertz (UNC-Charlotte) may have caught one of these ghosts: an elusive C=O copper pi complex. Using rapid-injection techniques at -100 degrees C, the team "freezes out" the complex, which they study by 2D NMR (which shows relative positions of various atoms) and cryoloop X-ray crystallography (shows absolute position in a fixed crystal lattice).

When the team warms the compound much above -10 degrees C, it immediately falls apart.

Isolating otherwise reactive intermediates lets us peer inside** the "black box" of catalysis. In this structure, the lithium atom tugs at the oxygen's lone pair, allowing the copper to slip into pi-coordination in a "side-on" fashion. Though it's tough to see from this picture (left), the authors point out that five atoms (O, C, Cu, Me-a, Me-b) all sit together in one plane, which validates earlier NMR models. Finally, there's some hints of reactive fate here, as the "bottom" methyl group shortens up, preparing to jump off the copper atom and onto the central carbon, while at the same time, the copper atom cozies up to the oxygen. Remarkable stuff.

* And that was just on one class of reactions!
**The deeper we look, the more crazy, head-scratching stuff we find. Ask your local organometallic enthusiast for more info...

Friday Fun: Super-Calcium!

Super-Calcium
Source: Niggemann Group, RWTH Aachen

I like to stroll through journals on quiet mornings, over coffee. After a few months, you start to see trends crop up: The Gold Rush. Carbon-carbon bond cleaving chemistries. Fluorine and boron everywhere.

A new trend almost snuck in under my radar: Calcium catalysis. In the past, a few groups had played around with amino-ene reactions, arylated tertiary alcohols, and made some enantioselective calcium pincer complexes. But I couldn't honestly tell you that I had branded any specific group with the "calcium" label, as opposed to the "palladium" or "organocatalysis" badges worn by many.

Well, the Niggemann group in Aachen, Germany appears to want that distinction. Prof. Meike and her team have released a slew of interesting reactions - Friedel / Crafts, [3+2] cyclizations, cyclopropanations - with more popping up seemingly monthly. But...calcium? The stuff ingrained in our bodies, stapled in the phosphate matrix of our bones and teeth? The stuff I eat in yogurt, milk, and cheese is now a catalyst?

Source: Niggemann Group, RWTH Aachen

Let's dig a bit deeper. To start, Niggemann's group uses a weakly-coordinated calcium complex, calcium (II) bistriflimide. Next, they exchange anions with a quaternary ammonium source, producing the "mixed" catalyst Ca(II) PF6 NTf2, increasing organic solubility. The group claims that this complex exhibits both high selectivity for olefin coordination and stability against air and moisture - both important properties if you're exploring new reactions!

This new catalyst combo, dubbed "Super-Calcium" (with mascot, above), reacts like a wild hybrid of alumnium, gold, and palladium. It activates alcohols as leaving groups (Al). It permits [1,2] hydride shifts (Pd). It's a hard enough Lewis acid to unzip donor-acceptor cyclopropanes, but soft enough to permit hydroarylation (Al / Au). Checking some of the historical calcium-catalysis reactions (above) reveals even more head-scratching reactivity reminiscent of magnesium, titanium, or vanadium.

So, what's really going on here? First, I'd say it's early days: Some deuterium-labeling studies were done on the older reactions, and molecular modeling on this latest batch, but several steps (Vinyl cations? Hydride shifts?) make me wonder exactly how intimately the central calcium atom gets involved. Second, no one yet knows the exact structures of these reagents in solution; look how long it took to figure out LDA!!! Third, Meike's battle cry rings mostly true: reactions exploring the reactivity of early alkali metals (potassium? barium?) remain largely terra incognita.

More reactions will lead to more interest; perhaps a Calcium Craze looms over the horizon? Time will tell.

Happy Friday, Everyone!
-SAO

Hey WIRED, Why No Chemistry Love?

101 Signals, WIRED Magazine's latest compilation of "...best reporters, writers, and thinkers on the Internet" just went live. They've broken down the list, which includes blogs, Twitter, and Tumblr feeds, into chunks: Business, Design, Consumer Tech, Gov't & Security, Culture, and Science.

Here's the Science group. A distinguished bunch, but guess what?
Not a chemist among them!!!

Sure, we've got great, well-known personalities like Ed Yong (Not Exactly Rocket Science) and Randall Munroe (xkcd), Phil Plait and Robert Krulwich. I see plenty of physicists, biologists, astronomers, geneticists, and science writers, but no chemists.
And yet, two Tumblr accounts with the word "f*ck" sprinkled in (Classy, WIRED, classy).

I suppose Maggie Koerth-Baker, who has written about chemistry several times, is the closest we get to full representation. But she's plugged as the BoingBoing science editor / NYT columnist, with nary a mention of chemistry to be found.

So, what gives? Folks on Twitter have suggested a few issues with the chemblogosphere, from "in-reach" in place of outreach, to a tendency to "punch-down," or even (gasp!) that our stuff just doesn't appeal to a mainstream audience.

All valid points. Well, allow me to retort: An aspect of chicken-and-the-egg surely works behind these listicles. Although we haven't fully ironed out all of chemistry bloggers' quirks yet, not featuring our blogs in mainstream offerings just exacerbates the problem!

How can we be part of the solution,* if we can't even get in the door?

In case a WIRED staffer happens upon this post, please consider the following widely-followed, high-quality chemistry blogs to include in your next collection:

In the Pipeline
ChemBark
Elemental
The Curious Wavefunction

*Please don't say, "If you're not part of the solution, you're part of the precipitate." We've all heard that one.

Also Appearing at...

Chad and Sam, brain trust over at The Collapsed Wavefunction, recently decided to have me over for some podcast magic. You'll have to go over there to experience the full effect, but let's just say it includes all of the following: Breaking Bad, Mythbusters, The Matrix, Jar-Jar Binks, Battlestar Galactica, Samuel L. Jackson, pending summer blockbusters, Jurassic Park, Francis Crick, and general tomfoolery.

What are you waiting for? Go have a listen!

Bonus: Make sure you stay through the end credits!

Podcast: Chemjobber, Stu, and SAO Discuss Plagiarism (Part 1)

Way back in February, Chemjobber and I sat down with Stuart Cantrill, Chief Editor of Nature Chemistry, for a chat about plagiarism in scientific publishing. We had so much fun talking that the recording ballooned into a 2-h epic podcast; I didn't know where to start editing!
Mea culpa - the conversation languished on my desktop, and I made excuses each week not to get it done.

Finally, Part 1 of the CJ / SC / SAO "Epic Podcast" arrives!



0:07 - Special guests
1:29 - Stu's day job: What happens to papers submitted to Nature Chem?
4:29 - How do you define #1?
8:19 - "Actually, actually, actually..."
10:42 - Journals already use plagiarism-checking software!?!
12:10 - (and get way too many submissions)
16:22 - Cantrill, automated.
18:47 - Who bears the cost of plagiarized papers?
22:50 - CJ's curious: What happens to the person caught copying?
28:12 - The self-correcting scientific literature
28:58 - Bloggers: A small group of people who care too much...
30:17 - Why publish or perish? Shouldn't it be quality, not quantity?
32:09 - Indexes (Indices?)
33:18 - Opening the door to Hour 2...

P.S. - If you need a primer, the earlier podcast CJ and I refer to is here.

JFK Scare: Analytical Chemistry at the Airport

Please see below for updates as I receive further information...

As reported by multiple news outlets (CNN, Daily Mail, The Atlantic), a 'suspicious package' leaked an unknown substance* onto two customs inspectors at JFK International Airport Sunday afternoon. When the workers fell ill, the FBI quarantined two facilities - one customs, one mail sorting - and tested the material.

Initial assays indicated potential organophosphate chemical weapons. Later tests, however, confirmed that the substance was actually phosphoric acid, leaking from a faulty cosmetics package. The two inspectors, after receiving on-scene treatment, declined further medical attention.

A few points about this story (emphasis mine):

• Most news agencies reported hesitantly, but not the Daily Mail, which declared: "The package from China tentatively tested positive for VX nerve gas, which can be used as a weapon of mass destruction..." (They even included a strangely-rotated space-filling model of VX in the article!)

I'd be quite interested to know how the FBI field tests for organophosphate nerve agents (Sorry, Daily Mail, but VX, due to its high boiling point and viscosity, is actually not a gas but a thick liquid much like phosphoric acid). I'm aware of certain colorimetric pesticide test strips, and certainly blood chemistry assays for exposed individuals would tell the tale.

But could phosphoric acid give a false positive here? Its chemical properties aren't overall very similar to nerve agent. Unlike VX, phosphoric acid has acidic protons, rendering a much different reactivity and solubility profile. VX soaks deep into skin due to its carbon appendages - hence, organophosphate - which wouldn't really occur with the acid. Perhaps JFK sent a sample out for 31P NMR? This analytical technique would show a resonance close to that of VX, which might incite a high-threat response. Perhaps an LC-MS might also ring warning bells: both compounds should show a fragment around 94 m/z.

• The Atlantic cheerfully summarized: "It turns out what made the two men sick was actually organophosphate, an ingredient in soda pop."

If I ever find organophosphate in my Coke can, I'm suing. That is, if I survive the encounter...

Organophosphates, to which VX, sarin, soman, and several potent insecticides belong, have alkylated (carbon-functionalized) bonds on their oxygen atoms. Once ingested or absorbed, they tend to interfere with acetylcholinesterase, an enzyme involved in neural signaling. The reporter perhaps meant to say "phosphorus compound" or even "acid," but unfortunately chose the wrong word.

One more thing: I completely understand the highly cautious nature of the law enforcement response. Organophosphates can sicken or kill at remarkably low doses, thus their unfortunate appeal as terror weapons. If any of my readers have experience with airport chemical detection, please write in to set me straight on your detection methods of choice.

Update, 8/12/13 - Changed "parent peak" to "fragment"

*Update 2, 8/12/13 - Chemjobber points out, via Twitter, that the NY Post reported ordinary nail polish remover (usually acetone, or ethyl acetate / iPA) as the culprit. Now I'm even more confused as to how this triggered a nerve agent analytical read!

Update 3, 8/12/13 - Commenters on Reddit and JLC (thanks!) remark that airports have at their disposal DART-based benchtop MS, or perhaps Barringer IONTRAP ion mobility spectrometers. Another commenter suggests M8-M9 detection paper. Vibrational spectroscopy (Raman, IR, etc) has been bandied about as well.

Book Review: Gulp

Note: For other reviews, check out Neurotic Psych, Science News, the New York Times, or the Boston Globe.

It took a bit longer than anticipated to finish Mary Roach's new book Gulp: Adventures on the Alimentary Canal.  Not any fault of hers - the book reads glibly enough, with just enough science to hold my interest (and just enough yuuuckk for wider audience appeal!).

Other reviews (see above) have explored the book's structure, which jokes hit or miss, and whether it holds water compared to Roach's other works. I'm going to take a slightly different take:

Gulp is a chemistry love story, wrapped in fart jokes and gallows humor.

As before, I'm just going to jump around to different chapters for moments I unexpectedly learned something about the unique chemistry of taste, smell, digestion, and excretion.

Page 44: "Pyrophosphates have been described [to author Roach] as 'cat crack.'"
(Finicky eater? Add some phosphates!)

Page 56: "A serving of liver provides half the RDA for vitamin C, three times the RDA for riboflavin, nine times the vitamin A in the average carrot, plus good amounts of vitamins B12, B6, and D, folic acid, and potassium."

"What's the main ingredient in dog food palatants? Liver."

Page 73: Huh: L-cysteine extracted from human hair has been used to make fake soy sauce.

Page 110: Baby saliva contains extra lipase, to compensate for "...the newborn's high-fat, 100% whole-milk diet."

Page 111: Fabric softener works by "...ever so gently digesting the fibers" using enzymes.
[Interestingly, howstuffworks.com, Wikipedia, and Answers.com seem to disagree, attributing the effect to static dispersal]

Page 142: Why does fruit crunch? "When you bite into an apple, the flesh deforms, and at a certain moment the cell walls burst."

Page 175: Oysters go into shock at low pH. Thus, "Researchers who need to sedate crustaceans use seltzer water."

Page 226: Apparently, in the early days of NASA space-flight, researchers expressed real concerns over capsule explosions due to methane and hydrogen gas produced during astronaut digestion.

Page 234: "Bean gas" results from complex oligosaccharides passing through the stomach and fermenting in the small intestine.

Page 245: Three sulfurous compounds contribute to most human flatulence odor: hydrogen sulfide, methanethiol, and dimethyl sulfide (the redolent-of-farts haze formed after a successful Swern oxidation.)

Page 247: Bismuth subgallate pills "...reduce 100% of sulfur gas odor, [functioning like an] 'internal deodorant.'"

Page 263: More on hydrogen sulfide, the "...hottest area in biomedicine right now: it's a gastrotrasmitter, a signaling molecule, [and] it has tremendous therapeutic value."

Page 275: Rats and rabbits engage in autocoprophagia - eating their own feces - as a method of supplementing vitamins (B5, B7, B12, thiamine, riboflavin) produced only by bacteria in their intestines.

Page 316: When processing "samples" for a stool transplant, a blender is modified to deoxygenate and store the material under nitrogen, thus promoting survival of anaerobic gut bacteria.

Overall, I really enjoyed the book, though I couldn't escape feeling that certain chapters (4, 11, 16?) had been shoehorned in from other projects only tangentially related to these "alimentary adventures." One interesting thing differentiating Roach's writing involves asides* to the reader, giving one the feeling that you're leaning in for a secret bit of wisdom...or an extra-terrible pun.

Seeing that Mary's last few books have dealt with (decidedly dirty) topics like death and digestion, I can only assume the next book will be titled Waste, and will uncover the exciting science of garbage and landfills.

If she writes it, I'll be first in line for a copy.

*Seriously, I know I'm supposed to 'kill my darlings' in writing, but I can't resist doing this sometimes...**
**Nor, apparently, can I resist ellipses. Dangit.

Friday Fun: Traveling Salesman

"Let's add some more zeroes to that number..."
Source: Mad Men | AMC

Out shilling for funds again. I've packed my book of spells, a suit, my voodoo doll, the rain stick, and a thesaurus. #phdlife #startup

— See Arr Oh (@SeeArrOh) August 8, 2013

Suit pressed.

Hair cut.

Shoes shined.

Marketing done.

Presentation saved to (one, two...) multiple USB drives.



...maybe I'll even have time for some chemistry today...

Wish me luck! 
Happy Friday, everyone.
-SAO

Enamine Double-Take

When I have a few minutes of down time at work, I like to flip through the most recent issue of C&EN.  Granted, it's been a busy summer, so I'm a few issues behind; I just cracked the cover of the July 29, 2013 issue today!

As I flipped through, an interesting-looking story covering fluorinated pyrrolidines caught my eye.
But wait, something's wrong here. Did you catch it?

Source: Enamine / C&EN July 29, 2013, p. 12

It just looks like a story! Someone clever over at the company matched the C&EN font, style, and text layout to camouflage their ad as a real story!

Well played, Enamine.

Coaching Science

Scrolling through my ACS Matters newsletter, I came across an interesting program I hadn't seen before:


The ACS Science Coach Program.

Participants in the program volunteer with a local elementary, middle, or high school, visiting at least six (6)
times, helping to plan labs and mentor young scientists. ACS even chips in a small grant ($500) to support the effort. Sounds like a cool program to me!

Just one question: Do you suppose the admins ever read the #ChemCoach carnival? [crosses fingers]

Update: Apparently, this dates back to pre-2011, so perhaps *I* subconsciously used *their* idea!

Valleytronics? More 'Borrowed' Phrasing...

Update: 8/9/13: Editors respond...

@SeeArrOh Thank you so much for this. We have taken notice, and we will act as soon as possible. @NatureNano
— Nature Materials (@NatureMaterials) August 9, 2013

***

Tonight must be "Twitter tipster" and "authors behaving badly" night!

From the 'News & Views' pages of two vaunted Nature publishing journals come the latest chunks of potentially plagiarized text. Please open your browsers to this 2012 Nature Nanotech article, and then this 2013 Nature Materials piece. Now, I'm not going to pretend I'm a p-chem or 'valleytronics' expert, but I can certainly spot duped text on command:

NN paragraph 2:

"Electrons travel through a crystal as waves, which are described by a momentum (which is a continuous variable) and a spin (which is a discrete index). It is possible for a crystal to have two or more crystal axes that differ in their orientation, but are otherwise identical: such axes can support electron waves that are also identical apart from their direction (or, more precisely, their momentum)."

NM paragraph 2:

"Electrons travel through a crystal as waves, which are described by a momentum (which is a continuous variable) and a spin (which is a discrete index). It is possible for a crystal to have two or more crystal axes that differ in their orientation, but are otherwise identical: such axes can support electron waves that are also identical apart from their direction (or, more precisely, their momentum)."

Missed the changes? There are none; this is lifted word-for-word.

Another, perhaps?

NN graf 3:

"As in spintronics, there are two main challenges facing researchers trying to make valleytronic devices. The first is restricting electrons to one quantum number, which for valleytronics means localizing them to one momentum valley. This is also referred to as achieving valley polarization. The second challenge is to detect the valley-polarized current."

NM graf 3:

"As in spintronics, there are two main challenges facing researchers trying to make valleytronic devices. The first is restricting electrons to one quantum number, which for valleytronics means localizing them to one momentum valley. This is also referred to as achieving valley polarization. The second challenge is to detect the valley-polarized current."

Hope you didn't blink much, 'cause that one's identical, too.

Although I don't excuse it, I can understand the pressure to grab text under a research deadline, or to emulate a master author. But for news write-ups?!? Looks like someone's got some 'splaining to do...

Cryptic Retraction, Uncovered

Earlier today, a curious Twitter tipster wondered aloud about an "obtuse retraction notice" in JACS:

"The structure of compound 1, the major compound, of the manuscript was mistakenly assigned. As a result the authors withdraw this manuscript."

You heard it right, folks: An entire (published) manuscript, all down to one set of spectra.

So, what went wrong here? Here's the carbon-13 spectrum, from the SI:

Source: Jang group | JACS 2008

Whoa! That's a lot of carbons for that relatively simple product. I count 39 signals, aside from solvent, despite the compound's formula - and the authors' peak lists - only accounting for 26.

Another tweet (thanks, Neil!) clued me in to this Organometallics paper, in which they prepare the same compound. Compare the spectrum above to this one:

Source: Hor group | Organometallics 2011

I count 26 major signals, about as many as should be there, given the slight magnetic inequivalency of the benzyl carbons.

So, what went wrong? One clue might be solvent; the first spectrum's taken in a highly polar solvent (d6-acetone), whereas #2 uses ol' NMR stand-by deuterated chloroform. Given the highly polar nature of the first compound, along with the extra signals (and perhaps a second benzyl group in the proton NMR), I'm guessing that spectrum #1 actually shows a quaternary ammonium salt, which might result from "over-benzylation" of the cinchonine starting material.

The real bummer here? I've looked through the rest of the SI, and most compounds appear spot on.

Certainly, the authors managed to perform a challenging radical addition with high selectivity. Even more curiously, the ammonium salt used to effect the transformation (1a) looks correct!

Tough pill to swallow. Kudos to the authors for making the right (tough) choice here, voluntary or not.

Update, 8/8/13: Over at Reddit, stop_chemistry_time has staged a fantastic, ongoing debate with me in the comments. Here's the link.

CPME? New to Me!

While reading through the latest Org. Lett. ASAPs, I came across a slick cross-coupling reported by the Walsh group (UPenn). The reaction unites acetamides and aryl chlorides, helped along by a "hybrid" Buchwald-Kwong pre-catalyst. Neat stuff.

Source: Org. Lett. | Walsh group

A certain passage caught my eye, midway down the second page (emphasis mine):

 "...four common solvents [toluene, cyclopentyl methyl ether (CPME), dioxane, and dimethoxyethane (DME)] were screened..."

All 'common' solvents, even CPME? I don't recall seeing that solvent in Trevor Laird's OPRD piece. Or on several solvent boiling point charts. In fact, I don't think I've ever used it...and I'm doing cross-couplings all day!

A quick literature dig on CPME turned up this OPRD, perhaps its grand introduction to the process scene. Looks like it exhibits several advantages over diethyl ether (higher boiling, lower peroxide formation), and improved safety metrics over dioxane or THF.

Readers: Am I just late to the game? Are process folks everywhere charging liters of CPME into reactors 24/7? Please clue me in.

Open Letter to Recruiters

Dear Biotech Recruiters:

Good morning! It's me, early-to-mid-career synthetic chemist with multiple first-author papers, Ph.D. / post-doc from a Top 10 program, and pharma job experience.

How's things?

I'm a bit worried that my emails and phone calls to you have gone unanswered since we'd last spoken. See, my (tiny) chemistry company could go bust at any moment, and I'd really like to have one of your jobs in my back pocket, y'know, just in case...

I'm not entirely sure who you're looking for, but I'm starting to think it's not me. I do apologize for having not been born 10 years earlier, when I could have taken full advantage of the '90s Biotech Boom.

Back then, doctoral degrees only took 4 years, and then you could jump out into a six-figure job designing drugs straightaway - no post-doc required! Project teams swelled up, thus you got listed on more patents and papers, and probably got all sorts of crazy performance incentives. (I won't even bring up stock options and signing bonuses, since they've mostly gone the way of the dodo). Those lucky folks are now eminently qualified, experienced, and well-connected. They're shoo-ins for any job you have listed.

Well, what about me? I'm young, hungry, internet-savvy and have pretty low salary expectations. I don't yet have a family, and I work tons of unpaid overtime.

I feel like I'm playing against a stacked deck, where everyone has Aces and Kings, but I'm stuck with Crazy Eights. Can I ever catch up?

Looking forward to your call,
-SAO