Saturday, December 3, 2016

Better Than Word of Mouth

Hello, dear readers. It's been...a while. I promise the blog is not dead, just sleeping for now. My 2017 New Year's resolutions include sculpting specific time out for all the sci-writing goodness. Stay tuned.

Enough maudlin overtures. Now, on to the fun!

Strem has, as any synthetic guru would attest, the highest-quality metal precursors in the biz.* Now, you could spend a weekend cracking ampoules to find out, or just open to the Supporting Information of one of Jeff Bode's recent publications in Org. Lett. Perhaps you remember this reaction - SnAP synthesis of saturated heterocycles - best from a cheeky Derek Lowe tweet:

That's in reference to the stoichiometric incorporation of tin** in the reagent, which serves as a linchpin for the eventual transmetalation to a copper species and ring closure, neatly without disturbance of the ipso heteroatomic group.

Well, much to my surprise, Prof. Bode has climbed on the recent trend of showing one's work through tactful inclusion of smartphone pics to buoy up procedure adoption. Especially with fussy transition metals, valency, contaminants, poor environment, and a whole host of other factors lead to catalyst poisoning and color changes. In the SnAP case, the litmus test seems to be formation of a correctly ligated Cu(II) ion in lutidine relative to the (probable) hexaaquo cuprate species formed as a blue heterogeneous train wreck.

The kicker? The fairly indiscreet preference for the Strem copper(II) precursor over all other suppliers. Look at the change! Night and day, and key to making these reactions work.

You couldn't buy better advertising than this....right, Strem?
Bravo, Bode group! I look forward to seeing your colorful coupling chemistry in future reads.


*Dear Strem: please send non-sequential $50 bills to See Arr Oh at Big City Company, USA
**SnAP. Get it? [drum kit]

Monday, August 29, 2016

A Tale by Mail

Long-time readers will no doubt be aware of my running affectation with the "Profiles, Pathways, and Dreams" series of books from ACS; books which, had I not read them in grad school, would probably cause this blog to never exist.

So I have a sneaky hobby: scouring the Internet's used book counter to assemble an entire set. Thus far, I've collected 17 of the 22 from the original 1990-1995 run. As I'm simultaneously trying for thrift, I'm proud to say the most I've paid for one of these books was around $25.

One of the best came in the mail only today - a first-edition, basically mint copy of Djerassi's Steroids Made it Possible. You know, the one with the picture of Nobelist R.B. Woodward going Mike Tyson's Punch-Out! on another esteemed chemist?

Steroids Made it Possible, ACS Books, p. 60

I open the plastic packaging, breathe in the old-book-paper smell.  But wait, there's no library markings. And the book is, what, 26 years old, and is basically undamaged? Curiously, I opened the cover, and realized that Djerassi himself had dedicated it:

To whom, exactly? Why, to Larry Lehmkuhl, the previous president of St. Jude Medical, according to Bloomberg. And is that really Carl's signature? I've compared it against two *for sale* on eBay and at Amazon - $89 euro and $39.85, as of this writing, respectively - it's the real McCoy.

This, of course, raises more questions: Did Lehmkuhl ever read his gift? Was he from a chemistry background? (I can't find much about him through the usual channels).

Did Djerassi mail out copies of his books, en masse, to anyone interested? If so, perhaps other signed treasures are out there, waiting to be found.

Sunday, August 21, 2016

ETC: Vonnegut, Djerassi, and a Mystery Polymer

I've recently finished the 1973 novel Breakfast of Champions, by acclaimed science fiction / humor writer Kurt Vonnegut. For those unfamiliar with Vonnegut's work, I enjoy drawing parallels* between him and "chemical provocateur" Carl Djerassi.

These two men share some odd similarities: born within 13 months of one another, each man suffered the Second World War - Djerassi as a refugee; Vonnegut as a POW - and had their personal lives scarred by young, tragic deaths in their families. Nevertheless, both became prolific writers of short stories, novels, and plays, and both lived to be elder statesmen in their chosen careers: Vonnegut to 85, and Djerassi to 91.

I'd even wager that they looked somewhat alike, with their bushy mustaches, well-coiffed hair, stylish clothing and impish eyes:

Novelist Kurt Vonnegut
Credit: Enotes

Chemist and writer Carl Djerassi
Credit: DLD / Stanford

Breakfast of Champions convinced me that Vonnegut may have had more than a passing fancy for chemistry, himself. Consider this hand-drawn rendering of a mystery plastic, ostensibly factory run-off that main character Kilgore Trout has unfortunately found stuck to his feet after wading through a river in Midland City, Michigan:

Credit: Kurt Vonnegut, Breakfast of Champions
Clearly, that's a cyanoacrylate co-polymer - think Superglue - and it seems to be drawn with a dendrimeric A-B-A architecture. I'm guessing that the ethylene glycol spacers (O-CH2-CH2-O) are meant to suggest the foaminess several characters encounter in the novel, that this mystery polymer is "...the stuff f***ing up Sacred Miracle Cave...", an in-book tourist trap overrun by large, odorous brown bubbles.

Incidentally, I love Vonnegut's inference for the continued polymer chain; where we chemists might write n, Vonnegut inserts his time-work "ETC."

Why? I'll let the author explain his philosophy:
"The man who taught me how to diagram a segment of a molecule of plastic was Professor Walter H. Stockmayer of Dartmouth College. He is a distinguished physical chemist, and an amusing and useful friend of mine. I did not make him up. I would like to be Professor Walter H. Stockmayer. He is a brilliant pianist. He skis like a dream.
 And when he sketched a plausible molecule, he indicated points where it would go on and on just as I have indicated them - with an abbreviation that means sameness without end.
 The proper ending for and story about people it seems to me, since life is now a polymer in which the Earth is wrapped so tightly, should be that same abbreviation . . .it is in order to acknowledge the continuity of that polymer that I begin so many sentences with 'And' and 'So,' and end so many paragraphs with '...and so on.' 
And so on. 'It's all like an ocean!' cried Dostoevski. I say it's all like cellophane."
Sometimes you encounter (surprisingly accurate) chemistry in places you didn't expect.
So it goes.

*Bonus: Here's Roald Hoffman interviewing both authors in a 1999 piece for American Scientist magazine

Monday, August 1, 2016

Enthusiasm Goes a Long Way

Earlier today, I watched a scientific speaker drive people out of the seminar room.

Was the person combative? Not at all; a well-respected mid-career chemist at a Top-5 school.
Unprepared? Nope; knew the slides backward and forwards.
Bad material? It was the linchpin talk of the session,
Perhaps haughty, egotistical, or rude? Still no - a model in professional conduct.

The talk was just, in a word...boring.

Source: Sydney Morning Herald

However exciting the science, you can't capture the audience if the delivery is dull as dishwater. Literally dozens of posts, listicles, humor attempts, even entire blogs (here, here) have been dedicated to the practice of scientific communication. So why don't these suggestions permeate into the wider community? Why do smart people not consider how their message comes across?

I won't go into the particulars of the talk I saw overmuch. Suffice to say that slumped shoulders, wooden expression, monotone delivery, and stiff arms will have your audience reaching for their smartphones in no time. Ditto: wordy slides, insider jargon, and attempts to somehow mash a 50-minute talk into a 30 minute time slot.

One wonders if, after a certain number of conferences, chemists have become inured to terrible talks. Perhaps we should consider installing a "canary" in the lecture hall "coalmine" - a speaking coach or senior faculty member, placed front and center, that can debrief the overall performance after the session, offer pointers, maybe even solicit feedback from the audience.

Optionally, what about Improv? Many fields - business consultants, customer service, construction, education - have benefited from comedy troupes teaching teams to think on their feet. Anyone have something like that occurring at their lab or university?

I'm not arguing that scientific talks be misconstrued as entertainment, yet I feel I could have learned more if I were actively on the edge of my seat, waiting to hear the next assay result or to see the next structure proof.

Anyone else agree?

Friday, July 29, 2016

Synthetic Endgame

Inspired by this paper from Melanie Sanford's rocking organometallic group at Michigan.

*Pun contest! I could also have called this post...

Gotta Make 'Em All
Poke-Ball and Stick Models
Chantix Charmander
Putting the Fun in C-H FUNctionalization
'All Thumbs' Synthesis

Friday Fun: Semi-Legal Starting Materials

I ran across this entertaining anecdote today while researching Lord Todd's research into vitamin B1.

From Todd's 1997 obituary in the Independent, written by fellow Nobelist "Kappa" Cornforth:
"[Todd] also worked on cannabis, and in his excellent autobiography A Time to Remember (1983) he tells with relish the story that, having naively imported 6 lb of distilled cannabis resin donated by the Indian police, he had to promise Customs that he would send 25 copies of any ensuing paper to their Bureau of Drugs and Indecent Publications."
Apparently, the "ask forgiveness, not permission" dictum applied in mid-1930s London. It bears reminding that this same choice, made today, would result the appearance of severe gentlemen in dark suits with thick briefcases and Summons in hand at the lab entrance...

Happy Friday,
See Arr Oh

Sunday, July 17, 2016

Undergrad Tech: Remember When?

Recently, I sat with a friend sipping coffee, watching passers-by hurriedly moving from one tall building to another. Remarks drifted back towards research - as they're wont to do when chatting with chemists - and she said: "Remember how hard it was just to order things?"

I knew exactly what she meant. Lab tech changes quickly, and you may not even notice until you take a step away from the bench. I'm not part of the generation who spent hours sketching molecules by hand from a rubber template pre-ChemDraw, but nor am I a grad student in the era of tablet computers that can access PDB or Aldrich from a free wireless connection in any lecture hall.

Maybe I'll take a quick stroll down memory lane to see how different things really were when I first started undergraduate research...

Planning: Then, as now, most projects kicked off using pen-and-paper or chalkboard sessions; whiteboards were in about 30% of classrooms and gaining ground, but my first experiences with drawing molecules for my coworkers covered my fingers in tacky powder. I can still smell lab chalk: musty, earthy, sometimes tinged with a faint amine odor if stored too near the reagents cabinet.

Courtesy of Dr. Freddy, at Synthetic Remarks, who seems to recall
chalkboards much more fondly than I.

Once you'd had the discussion, you transcribed it into a lab notebook - usually bound with black vinyl, perhaps featuring brown or maroon faux-leather accents and a bookmark string - and signed the page. Then it was time to dive into the literature. First, you staked out some territory at one of the few hulking beige monitors attached to your shared lab computers. Plan for coffee, since reboots and blue-screen crashes could usually be expected to last 10 minutes, with accompanying Windows jingles or goofy Mac cursor wheels.

(Why were operating systems always a generation behind on shared computers?)

Your 10-minute excuse to go grab a coffee.

Beilstein and SciFinder both offered installed systems with single-user seats. This meant you walked down your lab hallway, shouting "Does anyone need anything on SciFinder?" before logging in. The user interfaces were very Internet 1.0 - muted grey windows, inscrutable black text, fuzzy structures. Mostly, you would up transcribing the reference into your notebook alongside the idea. To get the paper, you usually brought a stack of dimes down to the reference library, and spent the next 20 minutes finding and then copying (don't forget to rotate every other page!) the journal article. The still-warm, toner-scented stapled copies were lugged back to your wooden desk to be pored over until evening. My fingers would often be tinged with more than one color of highlighter or colored pen after a night of intense study.

SciFinder Scholar, 1999. Source:

Synthesis: OK, you know what you want to make, so you need some reagents. Maybe first you glanced through the 2,000-row Excel file your lab has as its de facto "inventory" system. I remember some groups also had a dog-eared, yellowing notebook dangling from a rope of masking tape that listed all the chemicals no one needed any longer - hope you enjoy distillation! Failing these approaches, the trusty catalogs are all lined up against the single lab window, effectively blocking out 20% of the available visual real estate. Names of vendors I remember included Fisher, VWR, Aldrich, Sigma, TCI, and Columbia. Each one had different account reps, pricing, and delivery specs; you'd better believe your boss would ask if you looked up pricey, boutique reagents in more than one source. Someone had the lab job of calling these vendors every few days, providing the lab P.O. number or group credit card, and then taking delivery later that week. Collections of cardboard boxes large and small would be piled near the front door, and every week was Christmas (even if it was just your reagent-grade TEA).

The first and last physical Aldrich catalogs I remember ordering from.
Source: Alfred Bader, Sigma-Aldrich
At some point, you'd have everything needed to run your experiment. Hours passed, TLCs ran, and you scribbled long-hand in that same lined lab notebook. I'm fairly certain I spent thousands of hours hunched over, detailing exactly how the workup went, or scrawling single-line corrections (with initials!) for changes and errors.

Analysis: Instruments fell largely into two camps - things you ran and printed out to later affix into 3-ring binders, or numbers on an LED screen you hastily scribbled onto a Post-it note. UV-Vis and optical rotation fell into this latter camp; I still smile whenever I see a forgotten, tucked-away bookmark reading "+8.75 deg."

I worked in lab right at the death knell of chart-recorders - little red pens in threaded holders that traced a curve based on numeric readouts from an IR or GC. NMR, graciously, always emerged on an ink-jet printer in the corner of a sub-level lab. I was a Bruker shim-jockey for quite a while, bragging that I could shim, acquire, FT, pick, and integrate an 8-scan 1H in under 2 minutes. Of course, many academic labs now have robotic cherry-pickers and automatic data transfer, which must save tons of time (unless you're a biophysicist or monitor kinetics; we might as well chain you to the 600MHz).

Source: Cal State LA / Bruker Instruments

Presentation: My first lab group still owned an overhead transparency viewer, and we were encouraged to print or sketch acetate slides each week for discussion. As these smudged easily when warm or done hastily, there were many grumblings and thrown elbows at the photocopier from fellow labmates on group meeting day. PowerPoint was reserved for "big" talks - oral exams, defense seminars, or preparing a poster for ACS meetings. Once saved and laid out the way you wanted, these were burned onto a CD-R or stored on a 100MB USB flash drive your boss might loan you. The walk to FedEx felt tense, because you didn't want to lose this uncomfortable piece of plastic, which contained the only copy of your slides.
Just don't write on the glass itself, or the PI will get really angry. Trust me.
Source: Amazon

I'm sure that I'm missing more fun events from lab life and technology from the late 20th century. Readers, if you have a special memory from back in the day, please feel free to share it in the comments. I'll update the post if I've missed something vital.

Saturday, July 9, 2016

Big Fish, New Ponds?

Have you kept your ear to the ground? Felt something on the breeze? Getting a "gut feeling"?

The most recent edition of Chemistry Bumper Cars - Faculty Moves, for the uninitiated - leans towards bigger deals and dramatic poaches as the Fall term looms over the Summer horizon. Here's the latest I've heard about, with my own opinion about whether the rumor holds water.

Dave MacMillan to leave Princeton, for...?
Odds: Low

I hear what you're saying: MacMillan has already moved twice (Berkeley -> Caltech -> Princeton), and we're talking about a researcher who averages an award every year and a new named professorship every four. However, he's fairly well settled into a tight relationship with Merck, who are local to NJ. He's also helped propel Princeton back up in the rankings over the past decade. I can think of only one university that sounds like any kind of a step up, and they have plenty of organic power at the moment.

Dirk Trauner to NYU
Odds: Medium

Though I've heard this more than once, I'm scratching my head about how it makes sense for Trauner. Part of his motivation in returning to LMU was to continue the Mulzer mystique: the powerhouse European natural products group that makes densely-functionalized products appear as if by magic. Then again, NYU seems to be aggressively searching for a certain kind of chemist; maybe Dirk is slated to be the new Phil Baran of the East Coast?*

Update: As seen in the comments, Dirk himself confirms. My gracious thanks to the Professor.

Tom Rovis to Columbia
Odds: Certain

Signed, sealed, and delivered to Columbia back in the Spring.

Dave Liu to Broad from Harvard
Odds: Low

First he was an undergraduate wunderkind with Corey, now one of the youngest Full Professors and an HHMI scholar, all before age 40. He's already a core faculty member with Broad while managing his Harvard group, and I see no reason for Harvard (or for Liu) to wish to terminate his current position. This may sound like wild speculation or stargazing, but I fully suspect Liu's name goes on a nomination for a Big Prize within ~5 yrs, and I think Harvard would do everything they could to keep him in the fold for that day.

Update: As noted in the comments, does appear Liu will have to be physically present on the Broad's campus.

Karen Goldberg to leave U. Washington
Odds: Low

I very much want to believe, especially since UW lost Jim Mayer a few years back, that they can retain Goldberg, a C-H activation and general OM superstar. She boasts a local Center and a named professorship, as well as a Department with plenty of talented young blood: Boydston, Bush, Cossairt, Fu, Lalic, Schlenker, Theberge, Zalatan, all hired in just the last 6 years, doubtless some drawn there through her influence. I'm sure she'd succeed at a Caltech or an MIT, but I really don't know enough about her motivations to say any more conclusively.

Greg Verdine leaves Harvard to run companies full-time 
Odds: High

It's said you can throw a rock in Cambridge these days and hit a VC. Seeing how much apparent fun and success Verdine has had with his previous ventures into the private sector, I'm betting he continues this line full-time and slowly winds down managing theses and group meetings.

*Today's ridiculous statistic: In the past 20 years, Baran and Trauner have authored a combined 372 research papers. That's 2-3 entire careers, and these are guys with 20+ years ahead of them. Damn.

Tuesday, July 5, 2016

Sudden Tamiflu

Hey there, JLC fans! Long time, no post.

Today's inspiration comes from a molecule I've enjoyed watching the synthetic, process, and educational chemistry communities go to town on for the past 18 years: (-)-oseltamivir, also known by the trade name Tamiflu. See that cyclohexene in the middle? This molecule mimics the transition state of a mostly-flat oxonium cation derived from sialic acid, so well that it interrupts the flu virus's ability to release further infectious particles, allowing the body to "catch up" and reduce overall time spent hovered over a steaming bowl of chicken noodle soup.

But enough about the Why, let's get to the How; as the authors of this paper pitch in their opening line: Time is Money!

Hayashi and Ogasawara, no strangers to Tamiflu themselves (syntheses in 2009, 2010, and 2013), report in Org. Lett. ASAP a synthetic economy we don't always consider: time. They claim a one-pot Tamiflu synthesis, five steps, average step yield around 70%...finished in just 1 hour.*

Compare that against the benchmark of the previous 1-pot reaction - 57 hours. Wow!

Several interesting modifications to their previous syntheses have enabled this savings. First, addition of a hydrogen-bond donor catalyst to a nitro-Michael addition, which accelerates the reaction 3x. Second, swap of a base in an HWE reaction: 3.5 hours in cesium carbonate becomes 20 mins in tBuOK. Finally, a sacrificial move - rapid epimerization of the penultimate nitrohexene, knowing that only 50% of the product will successfully reduce to the desired diastereomer.** A short silica column completes the rapid realization of this antiviral drug.

Lest you believe that I'm hornswoggled by a synthetic sprint, a quick glance at the Supporting Info*** provides a cold shower. There's some lingering impurities in those 1H NMRs, enough to make me believe that the yield, even at gram-scale, isn't really 16%. And the reagent equivalencies used to drive these nitro-boosters aren't pretty: 30 parts Zn, 3 parts phosphonate, 15 aliquots of TMSCl. To touch upon an allusion the authors themselves make - perhaps a Jamison-style flow reactor is the next logical step for this speed-demon of a route.

*As I wrote this line, I couldn't stop comparing this to other "just 1 hour!" claims from consumer products: teeth whitening, photo development, tax preparation, LensCrafters, oil changes, and pizza delivery can all refer to the 2016 Hayashi Tamiflu synthesis as a spiritual brother of sorts.

**I don't believe that there's a spontaneous kinetic resolution here, but if any sharp-eyed reader can prove differently, I'm all ears.

***Counter-counterpoint: The one-pot is so streamlined that it now takes only 281 words to synthesize Tamiflu. 

Friday, May 6, 2016

Postdoc Required? Check the Job Ads!

Both the New York Times and C&EN have written pithy pieces today referencing the recent Science survey about factors influencing postdoctoral study. 

The tone of all three comes across as confused, painting Ph.D. students as ill-informed, directionless lambs who take on postdoctoral appointments as, in the words of the Science authors, "default...holding patterns" because they "...don't know what they want to do with their lives." (NYT).

Well, for those of us, like me, who postdoc'd with the intention of going into industry, why did I "waste my time in a post-doc" (Science) for seemingly no reason? Here's some telling quotes, highlighting from me:

From Science: " goals are quite diverse even among these postdoc-planning students...[t]his may be surprising, given that the postdoc is not typically considered a stepping-stone toward nonacademic careers"

From C&EN: "Many students don’t have a sense of how many jobs are available or what background they require, Doyle says. Chemistry students think they need a postdoc for some high-level industry jobs in the pharmaceutical industry, for example."

From NYT"[in 2013]...the most common reason students gave for doing a postdoc was that they thought it would increase the chances of getting the job they wanted."

These sound bites sound aloof at best, slightly pandering at worst. Here's my question: Did anyone quoted for this story, or the authors of the Science study themselves, actually read the job ads for the industrial positions in question? Maybe students' fears are well-justified, because the ads I'm seeing from multiple companies read like this:

GSK, API Chemistry Automation Team Member

Pfizer, Sr. Scientist - Obesity + Eating Disorders

Amgen, Scientist, Immuno-Oncology

Genentech, Sr Scientific Researcher, Discovery Ophthamology

In case you missed it, all recommend postdoctoral research. I didn't have to go digging for these, either - simply typing "chemistry" along with "postdoctoral" or "post-doc" into the Career search engine on any corporate site will reveal roles like these. I find it rather ironic that the last quote from the Science lead author reads: "We don’t know enough about the industry labor market” (C&EN write-up). That seems to be the only part of this whole situation I completely agree with. 

OK, grumpiness aside, how can this situation be fixed? I actually appreciate the incentive strategy advanced in the paper, which neither news outlet captured well. Here's most of the penultimate paragraph from Science, highlighting again mine:
"Whereas the recent National Academies report recommends that students make career plans early in the Ph.D. program, we argue that they should consider labor market conditions and career options before starting a Ph.D. program. Doing so may avoid escalating commitment to a research career and may prevent individuals from entering a postdoc holding pattern. Graduate schools could encourage career planning by requiring that applicants analyze different career options and justify why a Ph.D. is the most promising path forward. Funding agencies could implement similar requirements, especially in conjunction with moving a larger share of funding from research grants to training grants and individual fellowships."
Amen. One thing I believe saved me from five years of postdoc purgatory was walking in "eyes open," understanding exactly what jobs I'd qualify for and where I needed to end up to pay back all my student loans. I also realized it would be no cakewalk: I began applying for jobs in my second year of study, and never looked back. 

Grad students: If you're confused about your options, feel free to drop me an email at seearroh_AT_gmail. Confidentiality guaranteed.

Thursday, May 5, 2016

Two Billion Compounds?

I've been cracking my skull against a peculiar problem this week:
How many unique molecules compounds have ever been made?*

I'm referring to those produced by humankind, over the past 250 years - give or take a decade - of formal chemistry effort. CAS claims 100 million molecules in their collection, and predict, at the current rate of registration, another 650 million over the next 50 years.

Berries by the side of the road, 2016.
Not counted in billions.
Certainly other databases exist, a well-curated larger example being ChemSpider (34 million), but I'm sure the Venn diagram for that against CAS overlaps quite a bit. Ditto PubChem, which according to ChemConnector had over 37 million structures in 2009, but lots of errors, duplicates, and isotopomers, to hear him tell it. Outside the med-chem arena, there are exciting new collections such as the Aspuru-Guzik lab's Clean Energy Project, to identify photovoltaic materials. Surely the assembled collection of privately-held corporate data from all chemistry, pharma, biotech, and engineering firms must include another windfall; ~200 million compounds?

So, let's try a thought exercise - say we limit the set of what we call "made," or synthesized. We won't consider polymers, whether natural (DNA, polysaccharides) or artificial (Teflon, urethanes). Screening collections, libraries, and combinatorics; unless someone produced >1 mg, I'm leaving it out. Metal complexes and salts are in, since most of the time inorganic and formulations colleagues still produce quantities you can hold and measure (and get a melting point on!).

Granted, by referring explicitly to the public and private chemistry databases, I'm not including dark reactions, those failed experiments or perhaps non-optimal yields that never make it to publication. Based on my lab career (and that of my hood-mates), I'd say there's a comfortable 5-10 molecules made for every 1 that gets reported somewhere. Of course, since many of those are literature preps or repeat reactions, I don't think it inflates the count that much; truly, novel molecules tend to creep into papers and patents somehow.

Chemical space gurus, I apologize - I only want to count things that have been bottled, columned, purified, and analyzed. Large computational data sets of billions - unless they've been made and characterized - aren't up for consideration. Neither are metabolites isolated from plants or microbes; no fair counting what we relied on other organisms to make. S'posing this means we also leave out decomposition products and geological materials.

So them's the rules: 1 mg produced and characterized, non-polymeric, must have been made or produced with human hands. Salts and metals are in, along with isotopomers and stereoisomers.

What do readers and commenters think? My guess is in the title of this post.


*On the Twitter, Peter Kenny points out that I should, in truth, be asking after compounds, not molecules. Fair enough.
** Another reader points out that ZINC15, the database of "stuff you can buy now," only includes ~10M at present.

Sunday, May 1, 2016

X-Files' Freezing Catalyst: Digging Deeper

A random Friday afternoon link at Chemjobber's place clued me into Mitch's post, about a random NMR encountered in an old episode of '90s sci-fi classic The X-Files. By some odd coincidence I, too, was watching the episode sometime in early April, though I didn't get my notes and pictures together in time. Alas.

(Before we get too hung up on the episode's premise - that in 1996 computational chemists at MIT were performing in silico calculations on a "catalyst" intended for rapid body freezing - let's also remember that this episode shows us protagonist Lisa, a wunderkind doctor / chemist / radiologist, strutting out of her lab sans questioning after her patient spontaneously combusts!)

Now, to the structure of "Compound X" - I took a close-up of the computer terminal Lisa's working on, right around 17:00. Yes, folks, that's 1,2-dichloro-1,1,2,2-tetrahelio-ethane. Carbon-helium bonds can't exist, shout the skeptics? Well, 1993 marked production of the first He@C60 clathrate (story here), and friend of the blog Henry Rzepa had a theoretical paper in 2010 discussing charge-shift C-He bonding. True, isolable heliocarbons are still at large, for anyone seeking a high-risk, high-reward tenure project [ducks].

Molecular modeling has always looked best on Macs. There, I said it.
Fox Broadcasting Corp.

In his post, Mitch calls attention to the NMR, though I found the second analytical spectrum more entertaining, since it has an actual reference printed across the top. Turns out the producers did their homework for this one - this spectrum is an example of spectral linear combination to quantify small amounts of metabolites in blood plasma - good call!

Real science! In a sci-fi show! Who knew?
Fox Broadcasting Corp.

Back to the (flimsy) plot: certain details are over-the-top cheesy, like the "hand scanner" Jason uses to access his facility - it looks like it was built from an old dot-matrix calculator screen screwed into a subway post:

State-of-the-art security for the "MIT Biomedical Research Facility"
Alternate caption: I spent a weekend building this prop, and they used it for 4 seconds of footage.
Fox Broadcasting Corp.

The writers have also presaged the warm-liquid-goo-phase meme from Austin Powers, as the antidote to the freezing catalyst seems to be epinephrine, DMSO, electroshock...and complete-body immersion in a human-sized deep fryer:

Warm liquid goo phase - Complete!
Fox Broadcasting Corp.

Spoiler alert - the concluding scene, a conflagration in the "MIT computer mainframe," would likely have set the Schrock and Buchwald groups back quite a number of years.

Finally, I'll leave you with a silly futuristic quote: "The technology to engineer [Compound X] is still 5, 10 years away..." Sorry, Dr. Lisa - it's been 23 years since this episode aired, and to my knowledge, we're still not making per-heliated small molecules. Maybe check back in another three decades.

If you enjoyed this post, try some of the others in the Chemistry Movie Carnival from 2013.

Sunday, April 24, 2016

Feng Zhang's CRISPR "Miami Moment"

I've spent a bit of time this week trying to grok the ever-expanding frontier where biology meets chemistry. RNA therapeutics, chemical probes, synthetic biology, protein engineering...I could go on and on. Of course, this list would be woefully incomplete without the new cool kid: CRISPR.

If you've read a few of the stories surrounding this field's origins, you'll recognize the names Doudna, Charpentier, and Zhang. An interesting story arc emerges in the countless biographies surrounding Feng Zhang, now at MIT / Broad. Here, it's retold through the lens of WIRED author Amy Maxmen:
"Soon after starting [at the Broad], he heard a speaker at a scientific advisory board meeting mention Crispr. 'I was bored,' Zhang says, 'so as the researcher spoke, I just Googled it.' Then he went to Miami for an epigenetics conference, but he hardly left his hotel room. Instead, Zhang spent his time reading papers on Crispr and filling his notebook with sketches on ways to get Crispr and Cas9 into the human genome. “That was an extremely exciting weekend,” he says, smiling."
Have you ever had a point in your life like this?  Perhaps Zhang truly found the conference boring, and researching CRISPR was his best escape. However, since this story crops up so often, I'd like to think it's an attempt to capture the "flow" state as it applies to crystallization of a new field of research or career direction. Hopefully you recognize the feeling - total immersion, loss of time, tuning out all external concerns while your brain opens up to the vast possibilities of something truly new.

Clearly, a computer algorithm with a scientific sense of humor printed this lotto ticket. 

From my own experience, I can remember a handful of flow moments that I sustained for longer than a few hours. In the first, I spent two or three days reading everything I could about a competitor's catalysis research - hoping not to get scooped - and encountering multiple exciting ideas about monodentate ligand binding left unexplored. In another, I tried to track the entire Vinca metabolism from Tryp to the few hundred polycyclic alkaloids like vincristine and ajmaline. Plant metabolism turns out to be much more complex than I'd ever imagined.

Readers, I'm certainly not alone...can you recall when you've experienced a version of Feng's Miami moment? What was it like?

Wednesday, April 6, 2016

WWWTP? Math Non-profit Edition

Saw this "promoted Tweet" go by on the Twitterz earlier this evening.
But something just didn't add up.

Can you spot the problem?

Sunday, February 21, 2016

WWWTP? Slate "slate" Edition

A slate on Slate, a frustrated man next to a frustrated organic structure. The title?
"Teaching the Teachers."

Judging by his chemical acumen - yes, this man needs teaching. Desperately.

 How did he manage to make the western 1,4 diene without it slipping into conjugation?
Inquiring minds want to know.

Saturday, February 20, 2016

What's that Crud in My NMR Sample?


The reaction finished in 20 minutes by TLC. You grabbed a quick aliquot for LCMS; one peak! Quickly, you quenched, extracted, perhaps pushed through a silica plug for good measure. After concentration, a gorgeous white powder formed, so you pulled high vac for 20 minutes and rushed down to "get your proton on." But, darn it! Still wet with traces of, well, something...

Friends, has this ever happened to you? Trace impurities in otherwise perfect spectra lead to much head-scratching and SI docs labeled "final product_spectrum 5." 

The three papers linked to this post should help.

The new chart offers recommendations (colored arrows) based on Chem21 assessments of environmental impact, safety, and toxicity. Shown above are chemical shift tables (1H) in deuterated chloroform, acetone, and dimethyl sulfoxide.

If I were joining a synthetic lab this year, or starting an internship / work-study, I'd download 'em all and thumbtack liberally to the back of my bench. Guaranteed utility.

Friday, February 19, 2016

Chemistry Bumper Cars: 2016-2017

Sometimes great science means changing the view outside your office lab windows.
(Bonus: This usually comes with a new title and some filthy lucre, too!)

The people have spoken: last year's list has grown ungainly, and so it's time for a new batch.
Same rules apply: If you hear of a move, tell me in the comments, and I'll post in the "Pending Confirmation" section. Escape from pending purgatory involves sending me a link or other documentation from the new institution. Fair enough?


Trisha Andrew (Wisconsin to UMass)  two sources + email
Ryan Bailey (UIUC to Michigan)
Raychelle Burks (Doane to St. Edward's)*
Garnet Chan (Princeton to Caltech)  four sources + email
Andres Cisneros (Wayne State to UNT)  one source
William Dichtel (Cornell to Northwestern)
Guangbin Dong (UT Austin to Chicago)  thanks to five sources!
Greg Dudley (FSU to West Virginia, chair)
Daniel Everson (St. Olaf to CSU Chico)
Keir Fogarty (St. Olaf to High Point)
Tendai Gadzikwa (Zimbabwe / Alberta to Kansas State)
Vicki Grassian (Iowa to UCSD)
Carlos Guerrero (UCSD to BMS)
Zhongwu Guo (Wayne State to Florida)  two sources
R. Kip Guy (St. Jude to Kentucky, Admin) personal comm
Stephen Heller (Willamette to Loyola Marymount)
Kenneth Henderon (Notre Dame to Northeastern, Admin)
Rigoberto Hernandez (Georgia Tech to Johns Hopkins)  two sources
Tijana Ivanovic (Colorado to Brandeis)
Lisa Kendhammer (Georgia to CSU Chico)
Bern Kohler (Montana State to OSU)  two sources
Kristie Koski (Brown to UC Davis)
Chad Lewis (Cornell to Pfizer)
Roger Linington (UC-Santa Cruz to Simon Fraser)
Aimin Liu (Georgia State to UTSA)
Pamela Lundin (Wake Forest to High Point)
Anita Mattson (Ohio State to WPI)  three sources + DM
Mark McLaughlin (USF to West Virginia)
Andrew Phillips (Broad to C4 Therapeutics)
Alexander Radosevich (Penn State to MIT)  four sources
Jerome Robinson (Axalta to Brown)  three sources
Tomislav Rovis (Colo State to Columbia four sources + Twitter DM
Stuart Rowan (CWRU to Chicago) three sources + email
Emily Scott (Kansas to Michigan)  two  sources
Steve Soper (UNC to Kansas)
John Stanton (UT-Austin to Florida)
Eric Strieter (Wisconsin to UMass)  three sources
Alice Ting (MIT to Stanford)  many sources
Dave Thirumalai (Maryland to UT Austin, admin)
Dirk Trauner (LMU to NYU) Um...Dirk told me, and now there's a link! (Dec 2016)
Steven Wheeler (Texas A&M to Georgia)
Angela Wilson (UNT to MSU to NSF)

Pending Confirmation

Moved to 2017 list...


New Hires

Mitchell Anstey (Davidson)  one very specific source....
Nicole Ashpole (Mississippi Pharmacy)
Jonathan Barnes (Wash U St Louis)
Andrew Beharry (Toronto)
Eric Bloch (Delaware)
Lauren Buchanan (Vanderbilt)
Jessica Brown (Notre Dame)
Michael Campbell (Barnard)
Saumen Chakraborty (Ole Miss)
Ming Chen (Auburn)
Tai-Yen Chen (Cornell to Houston)
W. Seth Childers (Pitt)
Joseph Cotruvo (Penn State)  two sources
Mita Dasog (Dalhousie)
Alexander Dudnik (UC Davis)
Byron Farnum (Auburn)  two sources
Claire Filloux (UC Davis)
Aaron Frank (Michigan)
R. Aaron Garner (Penn State)
Nag Gavvalapalli (Georgetown)
Jing Gu (SDSU)
Will Gutekunst (Georgia Tech)
Osvaldo Gutierrez (Marylandone source
Anthony Shoji Hall (Johns Hopkins)
Katharine Harris (Curry)
Adam Holewinski (Colorado)
Joseph Houck (Penn State)
Xiaocheng Jiang (Tufts)
Miles Johnson (Richmond)  three sources
Julia Kalow (Northwestern)
Sarah Keanes (Michigan)
Aaron Kelly (Dalhousie, 2017)
Stefan Kilyanek (Arkansas)
Justin Kim (Dana Farber)
Ralph Kleiner (Princeton)
Jennifer Laaser (Pittone source + DM
Henry "Pete" La Pierre (Georgia Tech)
Hoang Le (Mississippi Pharmacy)  one source
Frank Leibfarth  (North Carolina)
Christina Li (Purdue)
Brian Liau (Harvard)
Song Lin (Cornell)
Steffen Lindert (Ohio State)
Xi Ling (Boston University)  two sources
Nian Liu (Georgia Tech)
Oana Luca (CU Boulder)
Charles Machan (Virginia)
Dionicio Martinez-Solorio (Drexel) two sources
Michael Marty (Arizona)
Karthish Mathiram (MIT Chem Eng)
James McKone (Pitt)
Evangelos Miliordos (Auburn)
Pere Miró (North Florida)  two sources
Sharon Neufeldt (Montana State)
Rodrigo Noriega (Utah)
Allie Obermeyer (Columbia)  two sources + DM + personal site
Carissa Perez Olson (WPI)
Alison Ondrus (CalTechtwo sources + email
Cedric Owens (Chapmanone source
Maria-Eirini Pandelia (Brandeis)
Kathryn Perrine (Michigan Tech)
Myles Poulin (Maryland)
Melanie Reber (Georgia)
Hans Renata (Scripps Florida)
Brenda Rubenstein (Brown)
Justin Sambur (Colo State)
Alina Schimpf (UCSD)
Valerie Schmidt (UCSD)
Ginger Shultz (Michigan)
Alexey Silakov (Penn State) personal comm
Jillian Smith-Carpenter (Fairfield)
Nick Stadie (Montana State) two sources
D. Cole Stevens (Mississippi Pharm)
Karin Stevens (Davidson)
Daniel Suess (MIT)  three sources
Ruby Sullan (Toronto)
Pratyush Tiwary (Maryland)
Darci Trader (Purdue) one source
Emily Tsui (Notre Dame)
Gael Ung (UConn)
James Van Deventer (Tufts)
Jesus Velazquez (UC Davis)
Lela Vukovic (UTEP)
Ross Wang (Temple)  two sources
Jessica White (Ohio)
Travis White (Ohio)
Heather Williamson (Xavier)  thanks, Ian!
Mark WB Wilson (Toronto)
Nathan Wittenberg (Lehigh)
Christina Woo (Harvardfive sources
Liz Wright (Barnard)
Min Xue (UC Riverside)
Mingxu You (UMass)
Michael Young (Toledo)  email
Lauren Zarzar (Penn State)  two sources
Bin Zhang (MIT)  two sources
Qiang Zhang (Wash State U)
Sen Zhang (Virginia)
Mingjiang Zhong  (Yale)

Pending Confirmation

Moved to 2017 list...


List covers Feb 2016 - Jan 2017 start dates

For 2015-2016 moves, click here
For 2014-2015 moves, click here.
For 2012-2013 moves, click here

*Bonus video!

Saturday, February 6, 2016

WWGS: What Would Gmelin Say?

Earlier tonight, I happened across a yellowed, dog-eared copy of The Rise and Development of Organic Chemistry, the 1894 opus* of Carl Schorlemmer, finished with help from his colleague Arthur Smithells. I didn't get a chance to read it cover to cover, but I appreciated a pithy quote in a postscript, purportedly an exchange between two chemistry heavyweights:
"When in 1829 it was found that pyro-uric and cyanuric acid were identical, Wöhler wrote to Liebig: 'Gmelin will say, Thank God, one acid less.'"
This, of course, in reference to Gmelin's attempt to gather the mid-1800s chemistry literature into a practical reference book. He would go on to create the Gmelin Inorganic Handbook, later to evolve into the Gmelin Database, part of modern-day Reaxys.

I appreciated the formal sentiment that pervades the text; certainly it's the first chemistry book I've seen that gives the reader a parting word after the index:

I'm sure I'll have more to say later on....there's some wild structures in this book, some that should give any serious bench chemist pause:

Aromatic endoperoxides? Egad.

*Just found out it's free online! Go here. Happy reading!

Tuesday, January 26, 2016

Tough-to-Swallow Propargylation

As I thumbed through the recent Tet Lett abstracts, I encountered this title:
"Regioselective propargylation of aldehydes using potassium allenyltrifluoroborate promoted by tonsil"
Turns out, the authors were referring to Tonsil (R), an acid-treated calcium bentonite clay, not the fleshy pockets in the back of the throat associated with immune response. I guess BRSM  doesn't have to update his "Desperate Conditions" list quite yet...

So, in summary:

Source: Sud-Chemie

Not This.

Monday, January 11, 2016

The NMR Laundromat

Source: OPRD / CNRS
The simplest, most practical solutions* are often the best.

I'm reminded of classic papers for pragmatic lab procedures, like Clark Still's on flash chromatography, or Gottlieb & Nudelman's on detecting trace NMR impurities. Everyone has encountered their lab's version of the Kugelrohr setup - run by an old electric kettle and a windshield-wiper motor!

From the ASAP of Organic Process Research and Development comes this handy one-pager: a how-to on cleaning dozens of NMR tubes simultaneously, using glassware readily available in just about any synth lab.

Seeing this instantly triggered a "Well, duh!" moment for me - the amount of time I've stood before a stoppered 500mL vacuum flask impaled with a cannula, washing single tubes by hand...I'm sure it reaches into hours, if not days.

If you try this, leave a comment; I'm really quite interested to see how it turns out. I'd also wonder if OPRD might be angling for other quick one-offs. Couldn't hurt to try, right?

*Of course, I'd be remiss if I didn't point unfamiliar readers to the treasure trove that is Not Voodoo.