Sunday, November 29, 2015

xkcd Quiz in the New Yorker

Source: Randall Munroe, for the New Yorker
If you haven't taken Randall Munroe's Thing Explainer quiz in the New Yorker, click on over for 5 minutes of fun.

I'm sure anyone reading this blog'll get a perfect score, but it's an interesting approach to scientific outreach all the same.

Click here to try your luck!

Molten Salt Bath, Anyone?

While paging through Organic Reactions, Vol 1 in the chemistry library*, I encountered some unusual conditions in a review of the Elbs reaction. If you're not familiar, it's a high-temperature pyrolysis** of ortho-tolyl ketones to produce polycyclic aromatic hydrocarbons (PAHs). Products produced from the reaction find use as analytical standards for oil processing, in studies of DNA intercalation, and as molecular wires.

PAH prepared by heating at 500 oC
Bonus: Roman numerals in older reviews? Classy, but confusing.
Source: Organic Reactions 1, p. 154
As alluded to above, the chemistry itself wasn't what caught my attention, but rather this sentence:
"The flask is charged with 152 g of the crude ketone and heated in a nitrate-nitrite bath (care!) a430 ± 5 oC."
Four hundred degrees! During all my years in lab, I can't remember heating reactions past about 300, and those were with machined blocks of aluminum on an ancient Thermo hotplate.*** 

I realize that pyrolysis technologies have advanced in 70 years' time - FVP permits higher temperatures for much shorter residence times - but the concept of a molten mixture of sodium nitrate and potassium nitrite seemed both dangerous and alluring.

This is either Hawaii's Mt. Kilauea, or a molten salt bath. Or both.

Looking through SciFinder, it seems that molten salt baths still find regular use in case-hardening and nitriding of steelwork, along with applications in cleaning organic residues off polymer extrusion dies. For extreme data-philes, the Molten Salts Research Center thoroughly analyzed a variety of salt mixture properties in a 150-page reference. Park Thermal International has published what seems to be a very conservative safety manual for nitrate-nitrite baths, and with good reason: aluminized leather aprons, tinted visors, and gauntlets help protect workers from glowing pools of salts at temperatures just below "decomposition...with extreme explosive violence."

Though I've never worked with molten salts, that doesn't mean none of my readers have. I see Milkshake has softened a 2L round-bottom flask by heating up to 380 with a graphite flake dry bath. How about you, Chemjobber?

Or are molten salt baths potential entrants in Derek's "Things I Won't Work With"?

Update (29 Nov): A commenter points out some previous Milkshake high-T campaigns.


*Real books! Complete with yellowing pages, musty smells, and indexes full of names like Fuson, Fieser, and Bachmann.
**Can't get enough Elbs? Curious readers are directed to Name Reactions for Carbocyclic Ring Formations, 2010, Jie Jack Li and Timothy T. Curran. Review starts on p. 324.
***Obviously not counting use of a butane torch to pull pipettes, heat sieves and salts, etc.

Friday, November 27, 2015

Chemistry from the Deep: Geomimicry

Hydrothermal vent
Lots of fascinating chemistry occurs in places humans can't routinely visit. Deep-sea hydrothermal vents, super-hot fissures formed from volcanic activity below the ocean floor, produce plumes of minerals and organic compounds. Through "geomimicry," researchers hope to harness similar conditions for use in labs here on dry land.

A team from Arizona State University - a geochemist, a biogeochemist, and a physical chemist  - report in JOC ASAP some interesting oxidation conditions using only copper salts and hot, pressurized water. With cupric chloride as an additive, benzyl alcohol and phenylacetic acid are oxidized to the corresponding benzaldehyde and benzoic acid in water at 250 Celsius and 40 bar (580 psi). The researchers speculate that the copper ions form different chloride species at high T and P, capable of promoting a series of single-electron transfers out of the organic substrates.

The article closes on an intriguing, somewhat humbling note:

"The vast majority of the organic material on Earth does not participate in the familiar, conventional surface carbon cycle because it is located deep within the crust and therefore undergoes chemical reactions under hydrothermal conditions. In contrast to the majority of reactions close to ambient [temperature and pressure], which tend to be controlled by enthalpic and kinetic factors, reactions...under geochemically relevant conditions tend to be controlled by entropic and thermodynamic forces...this suggests that much new useful organic chemistry may be geology."

In other words, the reactions and catalysis we tend to study in labs "above ground" are just the tip of the organic chemistry iceberg....err, volcano?

Monday, November 16, 2015

3D Recipe: Drug Design Meets Virtual Reality

I still remember the distinct sense of wonder upon seeing the first immersive chemistry visualization environments in pharmaceutical companies' hiring brochures. These culminated in CAVEs*, where groups of scientists could congregate, done special glasses, and be surrounded by room-size, manipulable molecules. Now, the promise of bringing virtual reality to every bench chemist seems a little closer, thanks to the Molecular Rift.

Source: UIC CAVE virtual environment

In last week's ASAP issue of the Journal of Chemical Information and Modeling, a team of researchers from Lund University (Sweden) and AstraZeneca teamed up to deliver a relatively inexpensive ($500) virtual reality setup based on the Oculus Rift, a VR headset, paired with the Microsoft Kinect, a motion sensor popularly used with the Xbox. The paper prescribes a collage of open-source software - including the video game engine Unity and the chemistry informatics package Open Babel - that the Swedish researchers utilize to model metal complexes and a CB1 receptor, complete with undulating ribbons of secondary structure.

Source: Lund University / AZ

So, what's the big advance here? It's all in the control: the Kinect sensor watches the user's hands, allowing navigation of the molecular model using intuitive hand gestures. This way, the chemist doesn't have to intrude on the immersive VR with keyboards, joysticks, or mouse clicks.

Hoping to "...stimulate further development in a collaborative fashion," the authors have released the source code to the public** through the open-source code repository GitHub. If you're among the first to try it out, drop me a line!

* Cave Automatic Virtual Environment. It wouldn't be software without a good recursive acronym...
**VR headset and Kinect sensor not included : )

Thursday, October 8, 2015

Chemistry Soliloquy

Good evening, honored blog readers. It's been pretty sparse 'round these parts lately.

Found at a country market out in the woods.
Perfect Fall sunflower.
Not to worry...I'm not hanging up my proverbial spurs just yet. But life sure is different, nearly two years into my latest #altchemjobs venture. Remember my initial post, where I couldn't quite come to terms with the size and intricacy of my new professional home?

Well, I still haven't.

It's a strange feeling: I spent nearly 14 years at the bench, setting up reactions, drawing schemes and mechanisms in ~20 line-ruled, hardcover lab notebooks with the respective companies' names etched in gold along the spine. I distilled solvents, sourced intermediates, rinsed reactors, and held forth at innumerable whiteboard (and chalkboard!) arrow-pushing sessions. At the end of the day, success was measured in off-white, crystalline powders and clear liquids in scintillation vials or crowded lab refrigerators.

I don't do much chemistry nowadays. At least, not the type you'd be familiar with from the foregoing description.
The script now unfolding? Facilitating chemistry - helping to transform thoughts, dreams, and ideas into reactions, systems, and products.

New cross-coupling? Let's invite in a consultant or speaker. Lab equipment? We'll get a prototype. Must-have software? Arrange some demos and evaluations. Along with the never-ending study that accompanies this career choice: stay abreast of the literature, learn from your competitors' mistakes, build your network out to compensate for the tangled web of interdependent departments in modern pharma. I can proudly say that I work with some of the smartest people I know, and I field calls from time zones all over the globe.

To paraphrase aprochrypha - "May you live in interesting times." And, I do. I really do.

Who could ask for anything more?

(More chemistry posts coming soon...whenever the 'interesting times' become slightly less hectic for a while...)

Wednesday, August 26, 2015

Giving Up Benzyne

From Rolf Huisgen's highly detailed and comprehensive biography The Adventure Playground of Mechanisms and Novel Reactions comes this rather eyebrow-lifting passage:
"I had several reasons for abandoning benzyne chemistry at the beginning of the 1960s. Many groups were active in the field, and other areas like 1,3-dipolar cycloaddition began to blossom in Munich. In addition, Georg Wittig, my venerated senior colleague, signaled in print and word that he regarded dehydrobenzene as his domain."

Left, benzyne, in one of its (many) accepted resonance forms
Right: Emeritus professor Rolf Huisgen, of dipolar cycloaddition fame

I wonder: Given the advances in benzyne chemistry over the past 112 years, and that up-and-coming groups make its study a central piece of their research portfolios, would this choice be made in today's research landscape? Readers, have you ever been asked to cease your studies in a certain area because someone more prestigious laid claim?

Tuesday, August 18, 2015

Fall ACS: Epic Tweet-up

Kudos to all who braved the blinding snow searing heat one-mile walk to Lucky's Lounge last night for the biggest ACS tweet-up on record (at least among the few I've attended!).

Folks I remember dropping by include:
N.B. Please toss me your name in the comments if I've inadvertently left you out!

@Dichtel, fresh off his Kavli lecture success
@SuperScienceGrl, our fierce vegetarian
@stephengdavey, Nature editor
@CrimsonAlkemist, polymers guy in sharp shirt
@DrRubidium, Communicator, Forensicist, superstar
@ChemProfCramer, needs no introduction to this crowd
Jeff Seeman, chemical historian extraordinaire
@curiouswavefn, molecular modeler and chief organizer

A candid shot from inside Lucky's
Names are withheld to protect the innocent.
@sciencegeist, professor and blog stalwart
@Free_Radical1, nice dude from DE
@UnstableIsotope, polymer chemist and sometimes spider-kitten
@gagliardi8, Modeler and fellow Italian
@petercarlton, keeps CAS social media in line. Also, Dungeness crabs.
@CMcCinDC, looks like Derek Lowe. Nice tie!
@Waghornscience, ACS videos star
@laurenkwolf, (also) famous for ACS vids and, y'know, editing, too!
@amandayarnell, (see above). Too popular.
@CHADNANO, Nano-ink Prof at NW
@MurphysLab, polymer defects, live from Canada
@barneygrubbs, the nicest, tallest tweep you'll meet
@JuliaKalow, MIT wunderkind
@katmatcher, another MIT wunderkind who helped vet reactions!
@CEN_Onion, secret secret, I got a secret (and no, he's not me)
@JamesBatteas, TAMU 2D polymer champ
@GriceChemistry, super-nice wrangler of undergrad research group

Thanks to all for a great night out!

Saturday, August 15, 2015

Hyperspeed Hyperforin

Kudos to the Maimone group (UC-Berkeley), who have published in JACS ASAP what seems to be the speediest synthesis of a hyperforin on record - just ten steps!

Perhaps this lends more credence to the Eastgate's "current complexity" index, which measures synthetic simplification over time thanks to improved methods. But who would have guessed that in just five short years this synthesis would telescope from 50 steps down to just 10? Strychnine, albeit a very different challenge, took nearly 60 years to simplify from 30 steps down to Vanderwal's highly-convergent six.

For Chemists: Steps of interest include a highly-oxidized [4+2] diketene cycloaddition, a iodoacetate-promoted ring expansion, and a highly modular synthesis widely amenable to analogue production.

For Everyone Else: Why should I care that this ungainly-looking molecule was made faster than before? First, hyperforin and related secondary metabolites (natural products produced by living organisms) isolated from famous folk remedy St. John's wort suggest new avenues for the treatment of of malaria and certain forms of depression. Second, if chemists can make variations on this molecule in roughly one-fifth the time, we can expect a venturesome start-up somewhere to begin fleshing out the SAR (what chemical modifications product what activities?) in record time.

Cellphone Charger Electrochemistry

I'm frankly amazed at chemists' rugged pragmatism. Our ilk often repurpose seemingly innocent household items - floodlights, LED strips, paraffin wax - adapting them for making new molecules in interesting ways. Have a peek at this new paper, which appeared* last week in Angewandte Chemie. 

The Aubé group, recently of UNC, wondered whether expensive setups from scientific vendors were potential roadblocks to wide adoption of electrochemistry. Their ideal recipe called for a direct current (DC) source capable of removing two electrons and an H from a lactam to generate an N-acyliminium ion. Looking around, the researchers realized that today's ubiquitous cellphone chargers might just do the trick. Shave back some wires, attach some copper clamps, and presto! Cheap, effective electrochemistry.**

Using their DIY e-chem setup, the Aubé group traps a wide variety of stereochemically-rich acyliminiums as the corresponding methanol adducts (19-93% yields). Now the real fun starts: there's a whole bunch of interesting arylations and other additions to these species one can access using off-the-shelf Lewis acids like titanium tetrachloride or boron trifluoride:

Adapted from Aube, Angewandte Chemie, 2015 ASAP

I'll be excited to see small libraries of diversified products emerge from this work. However, a "one-pot" functionalization - electrochemistry with the desired nucleophile already present - still seems a distant dream.

Hopefully, the apparent ease of operation of "cellphone charger e-chem" prompts other groups to give it a try. If your group dips their toes into this field, please drop me a line in the comments section.

*Thanks to Professor Brandon Findlay (@Chemtips) for pointing out this paper!

**I'm tickled pink at how many organic synthesis papers these days include photographic records of reaction setups. I'd like to believe that Blog Syn played a small role in advancing this change.

JLC at ACS Boston Next Week!

Still creepy.
Thanks, Carmen.

Excited as always to learn some new chemistry and stalk the Exhibition Hall at the 2015 ACS Fall Meeting.

I'll live-tweet a bit using the #ACSBoston hashtag. If you see anyone dressed like this (right), be sure to run the other way...

Looking forward to seeing some of you there!

UPDATE (15 Aug): From the shameless self-promotion desk, this request - if you're stalking the poster sessions or oral presentations, and you hear someone say "...and I'm so glad to be a new member of the faculty at Big State University!"

Please take a moment to jot that person's name down, and compare it against our ongoing collection. I'm willing to bet, ACS National Meetings being the social hotbeds they are, that a few faculty moves have slipped under the radar...

UPDATE 2: I hear tell that there's a tweet-up planned for Monday night. More details when I have them (and when I learn if I'm somehow interfering with others' plans!)

UPDATE 3: As announced on the Twitterz, one of my goals for this meeting is to befriend the venerable Professor Molenium, and somehow convince him to pose with me. If you spot the mole, be sure to tweet at me!


Friday, July 31, 2015

Friday Fun: Strained Conversation

This graphic was far too funny (to me, anyway) to leave buried in the graphical abstracts...

Courtesy of this Angewandte Chemie paper, in which we learn that "anti-Bredt" olefins - those C=C bonds located at the bridge of a caged bicyclic ring system - don't have to be discarded as possible structures for new natural products. The authors recommend their computational model, which uses modern forcefields to estimate olefin strain (OS) and predict stability of these bridgehead double bonds.

Happy Friday, everyone!
See Arr Oh

*I know this is a bit belated, but RIP P.v.R. Schleyer. You seemed like a really interesting guy.

Wednesday, July 29, 2015

"But...This Synthesis Goes Up to Eleven!"

Have you had fun reading through all the hilarious send-ups on the Twitter hashtag #HonestChemTitles? This tag tries to dig down to the subtext behind highfalutin words and strange symbols, uncovering the hidden motivations behind scientific papers.'s a hoot.

Remember the tweet that kicked off this brouhaha? A harmless convergent synthesis of some Lycopodium alkaloids. Kudos to @AlexFGoldberg for highlighting the authors' rather overblown title:

Classic children's literature;
my first exposure to superlatives
Amazingly, that 10-word title is 30% superlatives and 30% chemistry, with a smattering of conjunctions and articles to connect them. As others pointed out, how do you measure "elegantness," anyway? And when does a total synthesis cross the line from concise to exceedingly so; can anything more than a one-stepper be really succinct?

Sort through the paper with a grammarian's fine-toothed comb; one wonders if it wasn't run through some sort of excitement thesaurus, perhaps to get people really stoked about these routes.

Here's all the intense words and expressions I found:

Exceedingly concise and convergent

...and that's just in the first paragraph, folks.

Nigel Tufnel (Christopher Guest), ca. 1984
Honest opinion? Aside from the goofy title and superlatives liberally sprinkled into the text, the chemistry seems solid. Nothing's breathtaking - setting an early quaternary center through steric control is nice, and telescoping the three steps before the desired tetracyclic dione works well - but there's no "killer reaction" for me in this paper. The NMRs are clean, and the synthesis represents a decent improvement over existing methods.

Thus, I'd like to accept this publication into the "Spinal Tap Synthesis" category, so-named for the hard rock auteurs profiled in 1984's This is Spinal Tap, the tongue-in-cheek rock mockumentary. If you've never watched the movie, I won't spoil it, but I highly recommend the sequence in the middle where Nigel Tufnel, the vapid, misunderstood lead guitarist, obsesses over a "special" amp he designed that "goes to 11."

Fits this paper to a T.

Friday, July 17, 2015

Friday Potpourri: MegaMan, Lab Coats, More Worms

Please excuse my general lack of posting. When "Big Work Project" finally wraps, I'll have a bit more time for chemistry frivolity. In the meantime, how about a little collection of  almost-posts to help you into your weekend?


Faculty Fun: Maintaining a list of faculty moves can be tedious, but sometimes you find little gems on group pages. For example, Jeff Rinehart's group at UCSD will study magnetic materials. The logical mascot? A MegaMan master robot! (Vittorio would be so pleased...)


Last month, thought-provoking Chemistry World columnist Philip Ball wrote about white lab coats as badges of professional scientific stature. You may recall that one of my first posts here at JLC referred to the many ways in which such a white coat could be spoiled. I'm not exactly certain why - supplier availability, fire resistance, styling, cheaper? - but chemists in some younger synthetic organic chemistry groups seem to prefer blue lab coats.
Need evidence? Click below:

Phil Baran group
Stephenson group
Meek group
Shenvi group

(Readers: Know of more indigo-hued groups? Please mention in the comments)

Finally, for fans of vermisynthesis (who isn't?), you may notice that the chemblogosphere is giggling about this recent Tetrahedron paper on catalytic earthworms. Quintus points back to a 2014 PLoS One, but how far back have chemists truly considered the lowly earthworm as synthetic feedstock? Professor Leonardo Santos of the University of Talca, Chile, has investigated bioreduction of beta-carbolines since at least 2013. Perhaps he was inspired by the work of Kohji Ishihara, who published similar reductive behavior in cell-free worm extracts back in 2006. And both should potentially thank D.Q. Keiline, a reference in Ishihara's manuscript, who back in 1920 published "On the pharyngeal or salivary gland of the earthworm," which portended some of the proteolytic enzymes found therein.

Worm salivary glands ( in picture). You're welcome.
Source: Keiline, 1920

Tangentially, it's worth noting that an engineer in Colombia recently commercialized "biofilters" made of (living) earthworms, which clean organic solids from waste water. Seems someone should take a harder look at the potential catalytic goldmines wriggling underfoot.

Happy, squirmy Friday, everyone!
See Arr Oh

Thursday, July 9, 2015

What Happened to

A few years ago, folks on Twitter were helping me to collect a list of superlative chemistry authors - those in the rarefied air of hundreds to thousands of published scientific articles. At the time, I had counted Nobelist E.J. Corey's papers by visiting his personal website, linked from his Harvard emeritus faculty page

Curious, I returned there this week to view some of his recent research, and found this splash page:

1. Does this mean that the domain name is available?
(Checks - nope, someone has it, but GoDaddy will gladly sell you or!)

2. If you were the Harvard chemistry department, wouldn't you take steps to ensure that your emeriti had a guaranteed web presence? Prof. Dave Evans' fantastic site comes to mind.

Anyone have more information on when we can expect Prof. Corey's site to come back?

Tuesday, June 30, 2015

Smells Like Chemistry Prose

From the April 2015 issue of Wired magazine, two wonderfully redolent paragraphs regarding the flavor chemistry of yeast metabolites, courtesy of writer William Bostwick:
"The best sourdoughs command the same sort of cultish reverence as the best sour beers and for years were thought to come only from a few places. San Francisco's loaves are so famous, a Lactobacillus species is named after the city: L. sanfranciscensis, known for molecules like fruity isobutanol, butter-sweet acetoin, and grassy 1-hexanol."
If you're more a fan of lambics, perhaps this flavor profile better suits you:
"Pediococcus produces lactic acid, lambic's dominant flavor note, but can also emit funkier flavors such as buttery diacetyl. . . Brettanomyces also makes stuff like caprylic acid (goat smell) and ethyl lactate (horse-blanket smell). They're what make a farmhouse beer taste like a farm."
*(Title: Apologies to Nirvana).

Monday, June 29, 2015

(Please) Make More Molecules using Light!

Update (6/29) - Commenters chime in with some notables I'd mistakenly left off the list. I'll append their molecules to the end of this post (vide infra)...

I'm officially calling it: Photoredox catalysis = the new "it reaction" for organic chemistry.

Like many before it - iron catalysis, the gold rush, anything palladium, organocatalysis - photoredox catalysis is now appearing in my RSS feed on a near-hourly basis. We're in the early days of an exciting field; I've noticed more methodology papers and mechanistic studies lately. Assuming you start with a suitable aryl halide, diazonium, or carboxylic acid, the synthetic toolkit of single-electron catalysis seems virtually limitless.

Which begs the question . . .where are all the photoredox total syntheses?

Three examples of recent total syntheses that capitalize
on photoredox catalysis (bonds in red)
SciFinder: "photoredox total synthesis?"
7 hits.

How about "light-mediated total synthesis?"
7 more.

One more try: "photoredox natural products?"
7 hits.

Most of these hits actually lead to conference abstracts, not individual manuscripts. Props to the Stephenson group (Michigan), who leads the charge with syntheses of aspidosperma alkaloids and gliocladin C. Based on SciFinder results, I'd include the MacMillan synthesis of Lyrica, and Lei's isoquinoline syntheses from JOC.

Readers, what am I missing? A pivotal review or book? A group whose research is at the forefront of solar-powered natural product production? Perhaps a major non-English journal article? Any examples where a venerable old lion of total synthesis utilized a photoredox reaction alongside their Diels-Alders and aldol reactions?

For such a large-upside field, it sure seems quiet out there.
Update: Molecules made with photoredox catalysis, as suggested by my beloved commenters:

Overman, (-)-aplyviolene, Ru(bpy)3
MacMillan, fenofibrate (OK, not a np), Ni(II), Ir(III)
MacMillan, (-)-burshernin, Ru(bpy)3
Nicewicz, methylenolactocin and Protolichesterinic Acid, acridinium
Nicewicz, magnosalin + pellucidin A
Yoon, heitziamide A, Ru(bpz)3
Yoon, epiraikovenal, Ir(III)
Chen + Baran, sceptrin, Ir(ppz)3
Chen, nakamuric acid, Ir(ppy)3
Lawrence / Sherburn, endiandric acid A, kingianins A,D,F, kingianic acid E, Ru(bpy)3
Carreira, (+)-Daphmanidin E, Co-diimine (method here)


Friday, June 26, 2015

Friday Fun: Google Scholar Surprises

From Google, a.k.a. the guys with all the data, comes the most recent Google Scholar metrics.

I'm starting to really enjoy the level of specificity Google's learned around academic sub-fields. For instance, in my own sub-field of organic chemistry, who knew that Green Chemistry and Molecules were rising so quickly through the ranks of top-cited publications?

The h5-index Google's using seems like a shot across the bow of the venerable Thomson Reuters Impact Factor. A glance through the top-cited papers across all of chemistry, couched in this 5-year zetigeist, shows some surprising trends in the field: tunable materials, solar conversion, nanoparticles, and genomic medicine win the day - nary a major total synthesis among the top-cited 'scripts of any journal I could find.

If you have a minute, play around - the Google site is clean, easy to navigate, and provides direct links to publications of interest. If you stumble across anything surprising, let me know in the comments!

Happy searching, Happy Friday!
See Arr Oh

Sunday, June 21, 2015

How Long are Postdoctoral Fellowships? - Part 2

Following some interesting interactions with readers on Twitter and in the comments, it seems my initial post could have improved with 1) more data, and 2) break-down by gender. So, I spent some time this weekend digging through my last two Bumper Cars posts (2014-2015, 2015-2016) in order to provide a clearer picture.

How did we get here? Read the original post.

2015 - Random Trillium from a recent weekend hike

For starters, raw numbers - as of this writing, there are 194 confirmed new hires between the two lists. Of these, I was able to track down information about postdoctoral appointments for 132 (68%). Unfortunately, there's no consistent format for how candidates track their experience; I found myself cobbling it together from LinkedIn, university websites, ACS member profiles, and digital thesis repositories.

To keep myself honest, I'm pasting my assumptions below* this post, as before.

Now, to the numbers: First, the aggregate statistics - of the 132, here's the new mean/median/mode:

MEAN:3.49 years
MODE:3 years
MEDIAN3 years
MIN:             0 year (no postdoc!)
MAX:            9 years
(n = 132)

So, roughly in line with what I had before. But what about the gender gap? Do men spend significantly less time as postdoctoral scholars?

First, it helps to clarify what the real split looks like: Of 132 candidates, 39 (29.5%) are female. This may be an admittedly small data set, but I see only a slight difference** in overall time: 
3.47 years for men (n = 93), 3.54 years for women (n = 39).

Edit (6/21): A good spot to insert a quote from a 2013 Beth Halford piece in C&EN:
"For one, although there are no hard numbers to point to, some say people are spending more time in postdoctoral positions. In chemistry, one to two years used to be the norm, but that time frame may be creeping up. Some chemists tell C&EN that they are spending five or more years doing postdoctoral studies."
Seems to be the case, at least to me.

Of course, the best way to make this data set relevant is to send in even more new names! Once I can figure out a good mechanism to capture pharma / gov't hires, I'll try to expand the analysis. Who knows? Maybe we'll get a real live database set up...

*These postdocs reflect faculty appointments; I'm clearly not counting those who went into government, pharmaceutical, industry, or left chemistry entirely. If someone has a good idea for how to capture that data, I'm all ears.

Counting time: If someone gave a graduation year - "Ph.D. 2009"-  I assumed a postdoctoral stint until their faculty start date. For example, 2015 start = 6 years a postdoc. If, however, they provided a range - "postdoc 2012-2014" - I assumed that they postdoc'd the difference of that time, or 2 years, despite the fact that, depending on start and end dates, that could reasonably be interpreted as any length of time between 13 months (Dec 2012-Jan 2014) and 36 months (Jan 2012-Dec 2014).

Of the 77 new faculty starting in 2015 or 2016 (as of June 2015), I was only able to find bio-sketch information for half. The following people from my list are represented in the above statistics: Li, Engle, Hyster, Matson, Menard, Personick, Thoi, Tsui, Wasa, Blakemore, Browne, Devery, Gahlmann, Kempa, Limmer, Nelson, Sing, Thompson, Bantz, Hubbard, Garcia-Bosch, Huo, Wei Li, Mirica, Rossini, Seiple, Wu, Anand, Boudreau, Genereux, Jiang, Sletten, Theberge, Fu, Ke, Conley, Raston.

**One additional complicating factor? It's tough to tell who's a postdoc anymore. This study only includes candidates who list their experience as "postdoc", "postdoctoral fellow", "research associate", or something of that ilk. Senior researcher? NSF Fellow? Visiting researcher? Lab assistant? Are these postdoctoral positions, or not? Tough to tell, so I excluded them. Thus, I may be artificially shortening certain candidates' timelines.

Additionally, certain candidates had "gaps" of 1-2 years in their experience, and I could find no information for what they did. Took time off? Worked somewhere that didn't pan out? Had a child? I simply don't know.

Saturday, June 20, 2015

The Old Days at Org Syn

Thanks to a bevy of used book stores, I'm slowly completing my collection of Profiles, Pathways, and Dreams, the biographical essay series from editor Jeff Seeman. I recently re-read four of these: Cheves Walling, F.G. Stone, Raymond Lemieux, and the indomitable Jack Roberts' colorful collection of biographical anecdotes. Never one to pull a punch, Roberts wistfully recalls his first involvement with Organic Syntheses in the mid-1950s, then led by famous organic chemist Roger Adams:
"The modus operandi of Organic Syntheses is relatively simple. Much of the work is carried on by mail, and the editors meet twice a year for much of a day to assign preparations, work out difficulties, plan for future volumes, choose new editors, and the like, with the current editor-in-chief presiding. Following that meeting, the editors join with the editorial board for cocktails and dinner at one of the best (and most expensive) restaurants in town. In the old days, the dinner would be followed by . . .an Adams report on whatever was on his mind at the time. He often ribbed his colleagues, without malice, but nonetheless, severely. After Adams finished, the meetings often degenerated into the semblance of a stag smoker, with rounds of off-color jokes, the most tasteless of which usually came from the representatives of the publisher . . .Rather prodigious quantities of spirits, wines, and brandies were consumed, and some of organic chemistry's most renowned practitioners had to be helped off the scene. My first encounter with these bacchanalian festivities was in Atlantic City, in the spring of 1956. I made it back to my hotel under my own steam, but I spent the next day in bed, a lesson I did not forget."

This recollection sounds uncomfortably close to how I felt each time someone in my graduate group passed their oral examinations. Some things never change.

Wednesday, June 17, 2015

Lord of the (Small) Rings

Quick: What small, odd-looking thing carries metal through harsh trials?

Here's hoping you answered the Doyle group's new ligand: "Fro-DO."

I see what you did there.
Credit: Doyle group, JACS 2015

Unlike common sigma donors - NHCs, amines, phosphorous ligands - EDO (electron-deficient olefin) ligands function as pi-acceptors. Instead of dumping electron density into oxidative addition (adding an R-X bond across a metal atom) EDOs speed up* the other side of  catalysis, namely reductive elimination (joining the organic fragments and restoring the metal's electrons). According to the authors, acceleration of reductive elimination helps to decrease the amount of substrate decomposition due to beta-hydride elimination.

Doyle and coworker Dennis Huang report selective ring-opening of aziridines - no mean feat in itself -  and generate a quaternary center in the process, in 31-86% yields. Using a modified camphor-like sultam for their EDO, the group observes 27% ee, sure to be the focus of its own publication in the near future. Curious about related efforts in other groups? I recommend this Jamison mini-review.

Now, back to the name: "Fro-DO" carries the torch for a small-but-growing literature subculture. Chalk up another example to what The Atlantic recently called "Science's Love Affair with LOTR." I spent a few moments with SciFinder, trying to dig up some more chemistry-themed examples; the Atlantic points out many from geology and astronomy, and precious few from our molecular audience. Without further ado:

  • Superconducting magnets used in fusion research, controlled by codes nicknamed SARUMAN and GANDALF
  • A breast cancer gene marker, called "Frodo"
  • MRI pulse sequences, used to eliminate artifacts, also dubbed "FRODO"
  • Finally, a docking program for small molecules and RNA, with an apt name: "MORDOR"

Readers, any more chemistry-themed LOTR callbacks? Send 'em along!

*...or maybe not. An observant commenter on Reddit noticed that Doyle and colleagues see no correlation between 13C shift of the olefinic EDO carbons and reaction rate. They posit, instead, substantial steric congestion around the metal surface as responsible for the rate enhancement.

Tuesday, June 16, 2015

How Long are Postdoctoral Fellowships?

For a better analysis with more data, click here.

OK, apologies, chemblogosphere: today is apparently write-guest-posts-for-Chemjobber day.

He poses an interesting question in his "Ivory Filter Flask" post from earlier today:

What is the median length of a postdoc these days, anyways?"

Well, I may have some answers to that question. Looking through the New Hires, I put together a list, and ran some basic statistics*:

MEAN: 3.7 years
MODE: 3 years
MEDIAN 4 years
MIN:             1 year
MAX:            8 years
(n = 38)

It's tough to make general statements about such a small cohort, but I noticed two trends:

1) Disciplines such as chemical biology, nanomaterials, P-chem, and computational chemistry tended to stay in longer postdocs.

2) About 20% of the faculty profiles were in more than one postdoc or other fellowship program prior to their faculty appointment.

Thoughts? Sound right, or wrong? Please let me know in the comments!



These postdocs reflect pending faculty appointments; I'm clearly not counting those who went into government, pharmaceutical, industry, or left chemistry entirely. If someone has a good idea for how to capture that data, I'm all ears.

Counting time: If someone gave a graduation year - "Ph.D. 2009"-  I assumed a postdoctoral stint until their faculty start date. For example, 2015 start = 6 years a postdoc. If, however, they provided a range - "postdoc 2012-2014" - I assumed that they postdoc'd the difference of that time, or 2 years, despite the fact that, depending on start and end dates, that could reasonably be interpreted as any length of time between 13 months (Dec 2012-Jan 2014) and 36 months (Jan 2012-Dec 2014).

Of the 73 new faculty starting in 2015 or 2016 (as of June 2015), I was only able to find bio-sketch information for half. The following people from my list are represented in the above statistics: Li, Engle, Hyster, Matson, Menard, Personick, Thoi, Tsui, Wasa, Blakemore, Browne, Devery, Gahlmann, Kempa, Limmer, Nelson, Sing, Thompson, Bantz, Hubbard, Garcia-Bosch, Huo, Wei Li, Miller, Rossini, Seiple, Wu, Anand, Boudreau, Genereux, Jiang, Sletten, Theberge, Fu, Ke, Conley, Raston.

Scientific Phone Interview 101

Chemjobber has a post today asking for advice to improve success during phone interviews for scientific positions. As someone who's had to dip a toe in the interview stream several times in the past 5 years (and now routinely conducts phone interviews to fill openings in my department), I have some tips to add to CJ's arsenal:

1. (1 week prior) - Prepare.

    • As CJ points out, know who you'll be speaking with, and a rough idea of their backgrounds. Any public source is fair game: LinkedIn, SciFinder, Mendeley, etc. Bonus: If the lead interviewer has recently published something germane to the position, download the paper and see if you can piece together what they were trying to do.
    • Learn something about the company. Small, large? Private, public? Start-up? About how many people? Where do you fit in?
    • Can you prove you're the candidate for the job, sight unseen? Break down the job description into chunks, and match with your skills. This may sound hokey, but literally grab a sheet of paper, divide into two columns "What they want"  |  "What I have" and begin filling them in. Gaps? Be sure to explain how you'll address them.
    • If you don't have one, now's a great time to write up a Research Summary. Don't know how? It's easy! Condense each project you've worked on into one (1) synthetic scheme or graphic, with a plain-language description of no more than 2-3 sentences below. What were we trying to achieve? How did we do it? What did we learn?
2. (the night before) - Review.

    • Go over the information from Step 1.
    • Make sure you know your own CV / resume. Again, this sounds silly, but the recruiter may ask about anything you've listed, including something you don't think matters for the position in question: "Why did you choose that particular school? In Chem 257, did you happen to cover [my favorite reaction]? Tell me more about that volunteer gig from 5 years ago." 
    • Eat a good meal, get some sleep. In the morning, get ready as if you were attending an on-site interview. Say some lines to yourself in the mirror: "Hi, I'm Casey Smith, from Big State University. I'm really excited for this opportunity." Practice answering a few standard questions for yourself: Where do you want to be in five years? What do you know about the job or company? How have your skills and coursework prepared you to take this job?

3. (10 minutes before) - Relax.

    • Briefly review the Step 1 materials. By this point, they should be condensed into a short crib sheet.
    • Print out your CV / resume, so you can write things in the margins and understand what the interview team is looking at during the call.
    • Have a glass of water, clear your throat. Walk around or pace if it makes you feel better.
    • Be prepared to receive the call from 5 minutes early to 5 minutes late. Phone connections are tricky things, so be prepared in case you cut out (or the interviewer does). If you do not hear from them, be prepared to send an email that apologizes and requests a follow-up in the next 1-2 days.

4. (during) - Present.
    • Phone interviews are increasingly conducted "by committee;" don't be surprised if you end up on a conference line with 4 people. It's considered polite for the hiring company to introduce the call by introducing the people in the room and reiterating (briefly) the job description.
    • Politeness always. Please and thank you go a long way.
    • You should at this point know how to answer 80% of the questions your interviewer will ask, because you've already answered them for yourself. Experience? CV. Where you want to be in 5 years? Gap analysis - see Step 1. What you've done? Research Summary.
    • Take shorthand notes off to one side, because at some point, they'll ask if you have any questions. You MUST have at least one question! This shows interest in the position and a willingness to engage the speaker. 
    • Unless...your question is about an "HR" issue: pay, vacation, benefits, etc. Don't ask about these; you'll have a chance during the on-site.
    • Always send a thank-you email to acknowledge the interviewers' time and preparation, and be prepared for them to ask for further information.
That's it. Good luck!

Friday, June 12, 2015

Friday Fun: Greening Chromene Synthesis with a Surprise Solvent

Old adage in organic chemistry: "If nothing's happening, keep heating until something does."

A new paper from OPRD takes that advice to heart. The authors, chemists at Merck's Kenilworth discovery site, are attempting to make a difluorochromene as starting material for a gamma-secretase inhibitor. They identify a [3,3] propargyl Claisen reaction as a logical starting point:

Looks simple, right? Well, the original conditions call for heating the alkynyl precursor in N,N-diethylaniline (yuck!) at 195 degrees Celsius (wow!). And all that for a measly 35% yield at scale. From Kong, Meng, and Su:
"There were two challenges for this reaction on large scale: the poor yield and, in particular, substantial amounts of waste produced post reaction. To produce 1 kg of compound 1, we estimated the use of 25 L of N,N-diethylaniline as solvent, 40 L of 4 N HCl to wash away the basic solvent. Combined with the silica gel needed, such a reaction would create roughly 300 kg of solid and liquid waste."
What to do? The authors reason that decomposition of the solvent at such high temperatures might be inducing the starting material to polymerize. Searching for an inert, high-boiling solvent, they land on a run-of-the-mill lab standby: Silicone Oil.

Again, the authors:
"With excellent thermal stability and good heat transfer characteristics, silicone oil has long been used for oil baths in laboratories as well as refrigerants. It is also highly soluble in hydrocarbon solvents such as toluene and xylene as well as chlorinated hydrocarbons, and therefore, it should be a good solvent for nonpolar compounds such as 6 and 1. With the boiling point of 300 °C for silicone oil vs 220 °C for the desired product 1, it should also be possible to obtain compound 1 by distillation, eliminating the workup step and waste production."
Can't argue with any of that reasoning! Sure enough, heating their starting material under nitrogen in Aldrich high-temp silicone oil (14 mL / 1 g) leads to a 64% recovery of 90-95% pure product by distillation. Notably, the same oil can be pushed through a silica gel plug and immediately re-used, with no notable change in yield or color.

Given the sheer number of high-temp cyclizations - ene reactions, Diels-Alder, Cope rearrangements, alkyne trimers, Bergman cyclization - the authors bullishly predict further use of these relatively inert conditions to open up process-scale variants of these banner reactions.

Get your high-temp silicone's set to fly off the shelves this weekend!

Happy Friday,
See Arr Oh

Wednesday, June 3, 2015

WWWTP? BBC's Sherlock Edition

Chemical degradation by microscope? Incorrectly-scrawled structures? Wikipedia analyses?
Looks like Scotland Yard should send their consulting detective back to University.

I'm referring, of course, to Sherlock, the BBC reboot that re-imagines Detective Sherlock Holmes and his partner Dr. John H. Watson as modern* Londoners, with text messages and nicotine patches in place of telegrams and pipes. Quick reminder: the Sherlock of Sir Arthur Conan Doyle's original books represents the first fictional character ever recognized by the Royal Society of Chemistry for contributions to science.

Sherlock Holmes hacks into a secret British government database and finds...pyridine and phenol!
Credit: Benedict Cumberbatch and BBC-One

In "The Hounds of Baskerville," Holmes and Watson investigate claims of a giant, red-eyed monster lurking outside - wait for it - a secret military research laboratory called Baskerville. Naturally, the dynamic duo break into the lab under false pretenses, questioning a scientist accused of genetically re-engineering a pet bunny to glow green.**

They later return to Baskerville with a hypothesis: a psychoactive drug, perhaps hidden in an innocuous foodstuff. Holmes sets to work using the analytical instrument of choice for modern chemists - the light microscope. Using nothing more than a pipette and glass window that would have made Bob Woodward proud, Sherlock performs some crude chemical degradation studies:

Who needs NMR, kinetic studies, or a mass spectrometer? I have a mallet and a watch-glass.
Credit: BBC-One

(I'm guessing Sherlock wrote "D-Deuterium?" at the top left to remind himself that the evil research agency might have tried improving their mind-control drug's physicochemical properties : )

The silly Hollywood chemistry builds to a peak when Dr. Watson timidly investigates a scary chemical structure on the lab wall. Don't blink; it's only on-screen for about a second:

"Vancomycin" - Close enough for television?
Source: BBC-One
Well, at least the creators got something right - vancomycin certainly ranks as a "chemical weapon," but it's for killing marauding bacteria, not innocent townsfolk. That chlorocyclohexane on the right *should* be fully aromatic, and I'm sure if I had a higher-res image, I'd start to spot some more structural snafus.

I won't spoil any more of the show, but there's a few other chemical flights of fancy, such as Sherlock analyzing multiple components of floor wax using nothing more than some colored test tubes and his nose. Readers, cue up your online streaming service of choice, and have a look at episode 2.2 - let me know if I've missed more molecular mishaps.


* Spoiler - the goofy hat remains. Not a bad look, if you ask me.

**The show does mention that the green fluorescent protein was isolated from a jellyfish, which might be the most accurate science in the entire episode.

Tuesday, May 19, 2015

Buried Treasure

Regular readers know that I've been collecting names of chemistry faculty moves for a while now. I had to chuckle at this particular announcement, by friend of the blog (and fellow Tweeter) Prof. Karl Gademann. From two clicks deep on his group's home page:
"Prof. Gademann's first professorial appointment was at the EPFL in Lausanne, and he currently holds a chair at the University of Basel as a full professor. He has been elected to the board of the Swiss Academy of Sciences, and is affiliated to the National Centres of Competence in Research ‘Chemical Biology’ and ‘Molecular Systems Engineering’. Karl Gademann will move in Summer 2015 to the University of Zürich. His work has been recognized by a number of international awards, including the Latsis prize, the Novartis Early Career Award, the Ruzicka Medal, The Liebig Lecture by the German Chemical Society, and the European Young Investigator Award."
Thanks to an eagle-eyed commenter for the link.

Also, from both sites (UZH, BAS), it would appear that Dr. Gademann looks most professional when posed behind a rotovap condenser.

Best of luck in the new position, Karl - we'll add you to the list!

Monday, May 4, 2015


It's so refreshing that Spring has finally sprung in Big City, USA.

This one was snapped by an observant reader whilst on a
hunt for a new couch. Cost of each? $30.

Brewing Up Shikimic Acid

Could preparing Tamiflu starters be as simple as making your morning cappuccino?

The lab instrument in question,
straight from the Supporting Info
(I <3 pictures in SI)
Jason Smith and coworkers from the University of Tasmania have reported a PHWE - pressurized hot water extraction - to obtain shikimic acid, a common starting material in several routes to oseltamivir phosphate (Tamiflu). In a preparation that begs repetition, they grind up up 20 g of Chinese star anise, mix with sand, and quickly wash with a hot ethanol-water mixture using a household espresso maker (see right).

The researchers claim that, after a quick silica plug, they obtain 5.5% (w/w) of "sufficiently pure"* shikimic acid. I'd encourage you to go see the NMR spectra for yourself.

Of course, pressing common kitchen tools into synthetic service isn't news. My undergraduate lab group ordered many of its smaller-bore funnels and spatulae from a kitchen supply store. And let's not forget grindstone chemistry, popularized by the late Ajay Bose at the Stevens Institute of Technology, which used a stainless-steel blender** to combine solid reagents into heterocycles.

If molecular gastronomy involves bringing the techniques of organic and biochemistry into the kitchen, perhaps this represents its antipode, some sort of 'reverse' molecular gastronomy in which kitchen appliances and techniques inform bench science. Makes perfect sense; after all (say it with me)...Chemistry is Just Like Cooking!

*Based on the 1H NMR, I'm guessing their material hovers around 90% pure. Still good, given a 2-minute prep time. 
**Kitchen-Aid, no less - high-quality 'instruments' for high-quality chemistry : )

Wanted: Chemistry Humorists...err, Editors

Earlier this week, I took Angewandte Chemie to task: their (in)famous graphical abstract puns just weren't funny anymore. They responded with a job opening*, potentially to write exactly those puns I had just maligned. What a coincidence!

Chemistry writers of the world: Are you witty? Good at writing? Want to live in Germany?
Link's embedded in the Tweet.

*Sorry, Chemjobber, I know this is usually your beat, but I really couldn't resist.

Thursday, April 16, 2015

Spot-Checking Antibacterials in PLoS One

Update (April 17) - Commenters here and at Derek's place have set off alarm bells to potentially doctored spectra. Stay tuned...

Ever looked at a molecule and thought something was

A little while ago, I browsed through the latest edition of PLoS One, the open science journal. I don't often go there for chemistry publications, but curiosity struck, so I typed, "antibacterial NMR" (I think) into the search box. Up came this paper, from 2013, announcing:
  1. A novel alkaloid, xinghaiamine A, isolated from a marine bacterium, that...
  2. Had novel structural features, such as a sulfoxide and acenaphthylene ring, rarely seen, and...
  3. That showed decent lead activity against MRSA strains (2.7-5.5 uM MIC).
First thought: "Wow!" Second thought: "If this is so great, why is it buried in PLoS One?"

Then I happened to look at the proposed structure for this potential panacea:

Jiao, Zhang, Zhao, Hu, Suh, PLoS One, 2013

[Rubs eyes in disbelief].

Sulfonylated "ladderane" substructure.
A (4,7) disubstituted acenaphthylene bridge.
A previously-unknown-to-science (and virtually unknown to SciFinder) 4-4-5-6 ring system.
Can that really be correct?

Naturally, I made a model of one "half" of the presumed dimeric molecule:

Xinghaiamine A, pseudo-axial conformation,
assumed diastereomer of the (4-4-5-6) ring system.
The red circles are supposed to be bonded together...
I've taken apart and reassembled this molecule a few times, and can't seem to access any diastereomer that 1) looks energetically minimized, and 2) can actually have the acenaphthylene bridge the way the authors specify without "strain energy" popping out the plastic bonds.

Perusing the analyticals in the Supporting Information, I'm puzzled by a few more bits:

Jiao, Zhang, Zhao, Hu, Suh, PLoS One2013

The IR, briefly addressed in the text as suggestive of "[the] presence of a sulfoxide functional group" due to the 1082 cm-1 band, but contains peaks suggestive of:
  • alcohols, primary amines: 3383 cm-1 band
  • heteroaromatics: 743, 846 cm-1 band
The published 1H NMR has no peak labeling or integration (tsk, tsk).

That the COSY shows only one set of strong H/H correlations out of the 6 posited protons on the conjugated ring, which should not fit with the proposed structure. Nor should the seeming high symmetry of the ring fit with the proposed substitution.

Readers, what do you make of this? What kept this out of a more mainstream chemistry journal? 
Do you agree with the assigned structure? (Am I just shouting in the wind here?)

April 17 - Uh-oh...check out these anonymous commenters' finds on Derek's blog:
Potential editing of the H/H COSY

...and the HMBC