Thursday, January 31, 2013

Speaking of Surfactants

Looks like Australia got quite the bubble bath!

Tropical Cyclone Oswald, which passed by the eastern coast earlier this week, left in its wake a mass of fluffy, off-white sea foam, which the Atlantic Cities blog commented "[smelled] like the underside of a flatulent elephant seal." The foam, piles of which measured several feet tall, stalled commutes and rendered certain city streets nearly impassable:

Beach scene
YouTube - "Foam Day"
From AP / USA Today

So, what's causing this frothy mess? Two possibilities: either lignans and lipids from offshore algae, or decaying organic matter washed out to sea from land. The surfactant activity of the biomaterials, combined with rapid water agitation by the storm, have whipped up some stinky suds.

WWWTP? "Third-Party" Edition

Source: Kishida Chemical
A blog buddy sent along this puckish reminder of customer perception in the crowded chemical sourcing market. Seems Oakwood Chemical, a U.S.-based supplier, recently partnered with Kishida, a Japanese fine chemicals company.

Kishida specializes in med-chem building blocks, but seems to have a problem with their structure-drawing program (right)...where did all the hydrogens go? Don't think it's just on the website - the catalog goes 50/50 for abnormal heteroatom saturation.*

Readers, am I missing something (other than those "H" atoms)? Is this part of some common fragment representation, or is it just lazy drawing?

Comments welcome.

*For a good time, check cyclobutylhydrazine dihydrochloride (PK0-13441), which seems to be missing a record five (5) hydrogens! Can anyone top that?

Wednesday, January 30, 2013

Nitration Surprise

(File under "Learn something new every day")

Boom goes the peptide!

For some light bedtime reading, I chose Life Technologies' Molecular Probes handbook, a 1,000-page opus of how to make anything and everything biological light up in brilliant hues of Texas Red or Cascade Blue. Flipping to Chapter 1, I quickly glanced at the very first scheme in the entire catalog, and did a double-take: tyrosine tetranitromethane!

TNM: First time's the charm!
Source: Molecular Probes Handbook
Not to tread on Derek - who has a good thing going with his "Things I Won't Work With" tales - but doesn't this look like it should be grandfathered in to his list?

"Rule of Six" violation? Check. Potentially explosive byproducts? Check Check. A brief glance at the MSDS shows some of the more exciting Hazard Codes ("H330 - Fatal if Inhaled"), and the Merck Index (#9305) ain't much better: TNM "attacks iron, copper, brass, and rubber" and "Has been proposed as [an] irritant war gas."


But, lest I lapse into my own fit of hypocritical chemophobia, I should point out that this compound is apparently 'par for the course' for stalwart chemical biologists - it's been used since the 1920s to label proteins, and a 1966 JACS article dubs it "stable, specific, and gentle." Even PubMed brings up >600 references, so I suppose my initial gut-check was a bit unwarranted - TNM looks OK when used in dilute solutions. But, I'd still say you should think twice before considering it for routine bench work.

Tuesday, January 29, 2013

Science Online Contact High

Well, folks, it's that time of year again: ScienceOnline 2013. I know Bora's all psyched up, and Ash, Carmen, and Dr. Rb all have fantastic sessions cued up. Wish I could be there to enjoy it in person!

Maybe next year, assuming our podcasts improve, CJ and I can moderate a session (Topic TBA, naturally). Until then, enjoy your Carolina BBQ, and remember the difference between "y'all" (second person singular) and "all y'all" (second or third person plural). Have some hush puppies, too!

Sunday, January 27, 2013

Travel Channel Chemistry

The dry cleaning bills must have been
a nightmare.
Source: Travel Channel
Somehow, I missed one of the recent Mysteries at the Museum episodes in last month's holiday hullabaloo. Did you catch it?

Featuring Jennifer Landry, Director of the Chemical Heritage Foundation museum in Philadelphia, the piece profiles young W.H. Perkin as he isolates and later conquers fashion with his revolutionary synthetic dye, mauveine.

I'm grateful to have more chemistry-themed shows appear on TV, but I do have one tiny quibble: do you suppose a dye chemist would have such crisp white sleeves?

Check it out, and let me know what you think.

JLC to JPL: Huh?

Readers, help me out here: what am I missing about this NASA-JPL press release? (thanks to Phenomena for the tip). I mean, I grok where they're trying to go - investigating OOL chemistry through construction of a hydrothermal vent simulator - but the text feels all jumbled-up! For instance:

"Scientists with the NASA Astrobiology Institute's JPL Icy Worlds team have built this series of glass tubes, thin barrels and valves with a laser and a detector system"

Wait, they built it with a laser? (Must be for the spot-welds)

"They want to see if sending these two liquids through a sample of rock that simulates ancient volcanic ocean crust can lead to the formation of simple organic molecules such as ethane and methane, and amino acids, biologically important organic molecules. Scientists have long considered these compounds the precursor ingredients for what later led to chains of RNA, DNA and microbes."

Hang on just a second, that sounds rather confusing, NASA. I think you mean complex molecule generation paves the way for future complexity. Methane, ethane, and amino acids aren't going to spontaneously assemble into DNA. Ever.

That word, "ancient,"
I do not think it means what you think it means...
"This experiment has its roots in a theory from Russell in 1989 that moderately warm, alkaline hydrothermal vents at the bottom of the ocean could have hatched life about 4 billion years ago. The ancient ocean at these vents contains carbon dioxide, which provides the supply of carbon that could be reassembled into organic molecules."

"Ancient Ocean?" Is there a secret time-bubble hidden deep in the present-day mid-Atlantic? In case you're counting, they use the clunky 'organic molecules' some six times in the release.

"Scientists will alternately send the two solutions through a thin barrel of iron-magnesium-silica-volcanic-type rock that was synthesized by Shibuya..."

A what? A zeolite, maybe? There are so many qualifiers in that adjective conglomeration, I can't even figure out whether it's really a rock...

Source: NASA JPL
Also, PPE alert: If you're showing off your experiment, which is under pressure (100 atm) and heat (near to boiling), wear your goggles! We don't want Jyllian including you in the weekly round-up!

OK, maybe I'm being too harsh. In no way do I mean to impugn the actual science, which seems fascinating, just the strange retelling of it. 

But hang on, aren't these the same folks (NASA Astrobiology Institute) who wrote that "Extraterrestrial Life on Earth" presser just two years ago? We all know how that turned out

One would think they'd be very careful wording future releases.

Saturday, January 26, 2013

Some Thoughts on BVO Writeups

Hello there, 'science beat' journalists! I hear that Gatorade* just announced it would eliminate brominated vegetable oil (BVO) from its ingredients list (guess that chemophobic petition really worked, huh?)

Well, this is a chemistry blog, and I feel my skin crawl watching various scientific terms and concepts flying around sans context. So, let's set a few things right:

  • Bromide, bromine, and brominated all refer to elemental bromine, but they aren't interchangeable terms! Bromide refers to a single bromine atom with a full octet of electrons [reduced, or "Br(-)"], and is usually found in ionic salts (e.g. potassium or sodium bromide). Bromine refers to the element itself, a corrosive brown liquid. "Brominated" refers to a compound, usually carbon-based, that contains bromine atoms. Now you know.
  • Just because you cite the 2011 Scientific American article regarding BVO overexposure does not mean you've vetted the science! I've looked all over (WebMD, PubMed, SciFinder) for incidences of BVO poisoning, overdose, or excessive consumption, and I find...two. The 2003 NEJM (Ruby Red Squirt), and the 1997 J. Clin. Toxicol. (2-4 L of cola daily). Please don't say "a few" or "some" when you mean two.
  • Emulsifiers, such as BVO, don't "weigh down" or "sink" the citrus oil - they emulsify it! That means they help to disperse one liquid into another liquid, by promoting formation of tiny droplets of one inside the other. And it's not the use of "heavy" bromine atoms that does this, either. Even if it were, at 8 ppm (8 molecules BVO per ~1,000,000 of water), that's not a lot of mass! It's physics, folks. **Update (1/27/2013) -OK, you win this one, Internet! BVO really is a "weighting agent," and I won't harp on this point. Thanks, Prof. Kass. 
  • Chemophobia: Do we really have to have "chemical" in every lede? Much less reference the well-worn 'fire retardant' factoid? I'll tell you about another "fire-retardant chemical" widely found in soft's called water.
Hope this helps!

*A Pepsico brand, although some media relations person obviously told them to expunge all references to BVO or 'brominated' from their parent site...try the search box!

***Update (1/30/13) - CNN's coverage seems to have eschewed science to focus on PR reps and corporate statements: "...bromine is cited in some chemical company patents as a flame retardant." Sigh.

WWWTP? MedChemComm Edition

E tu, Pfizer? Sheesh.
Modified from MedChemComm, 2013
Blogosphere buds Chemjobber and Organometallica took turns finding "eccentricities" in a recent MedChemComm cartoon abstract (right). OK, I get it, a hilarious cartoon of the liver as a ravenous monster, chewing up your precious drug leads...

But look closer: What on Earth is up with that structure? As CJ / OM pointed out, we've got chain breaks, Texas carbons, neutral four-coordinate amines, floating atoms, the works!

Now, this review looks to have been scribed by some heavy hitters - two Pfizer PK folks, and two medicinal chemists. Worse still? Both med chemists are from top-flight groups (Nicolaou and Corey), and I've profiled one of 'em over at my place.

So, caveat auctor - If you're listed as part of a multi-author review, always check it over* before someone else submits it! "Only YOU Can Prevent Unwanted Blogosphere Satire."

*And chemists, don't let non-chemists draw molecules for you, especially if they end up in scientific papers!

Friday, January 25, 2013

Friday Fun: Dog Guru

To celebrate some blog-related metrics a few days ago, a dedicated coterie of chemistry Tweeps took turns defacing augmenting my trusty blog alter-ego, using the hashtag #PhotoshopTheDog.

Here's a few of my favorites:
Chemjobber used the 'high-tech' MS Paint
program to make me look like a pilgrim
Brandon argued for a fearsome mustache.
Alex gave me a diploma.
(I think I look like Dizzy Gillespie!)
I have no words, Vittorio. (My words, gone they are)
WINNER! (And eerily plausible-looking)
Happy Friday, Everyone!

Thursday, January 24, 2013

Prof. Daniel Havey, 34

source: Chemjobber
This post puts a rather final note on the emotional "Grad School Mental Health" discussion many of us wrote about two weeks ago.

A few days ago, I received a tip from a trusted source about the 'sudden passing' of a (very) young professor. A brief search confirmed the worst: Prof. Daniel Havey, a physical / atmospheric chemist at James Madison University, dead at 34. Requiescat in pacem. Further reports, passed along from the JMU Breeze, indicated that he had committed suicide. He was found in his lab.

What a tragedy.

We don't yet know why Dan felt such grief. I'm sure more details will emerge in the coming weeks. However, on the heels of our discussions earlier this month, I must speak up: we work in a highly stressful field, and the mental health of yourself and your coworkers should be of utmost concern. If you've ever felt like you can't go on, get help! Please.

In an ideal world, we'd all be writing fewer posts like these. Be well, everyone. -SAO

Wednesday, January 23, 2013

Here We Go Again!

Well, it's been about 12 hours, and the internet 'done blown up' over allegations of plagiarism between a 2013 Chem. Eur.J. and a 2009 JACS. Now, let's say that all this blog coverage brings a lot of otherwise-unwanted attention to your group, and people start to notice other similarities...

...such as the ones between a 2012 Dalton Trans. (same gentleman) and a 2010 JACS, this time from Chuan He's group over at the University of Chicago. Holding these up face-to-face, there sure are a bunch of similarities (again!).

He (p. 2): "In this study an Amt1-based copper(I) fluorescent reporter, Amt1-FRET, was constructed by subcloning the copper-binding domain of Amt1 (residues 36-110) between a cyan fluorescent protein (CFP) and a yellow fluorescent protein (YFP), taking advantage of the copper(I)-binding-induced conformational change of Amt1 (Figure 1b). This strategy, pioneered by Tsien and co-workers, produces a genetically encoded fluorescent reporter by inserting a sensing domain, which undergoes a conformational change upon target binding, between two fluorescent proteins that are fluorescence resonance energy transfer (FRET) pairs.10,11,21 Amt1-FRET was expressed in E. coli in the presence of 1.4 mM CuSO4 and purified to yield the copper(I)-bound Amt1-FRET (Amt1-FRET-Cu) (Figure S2, Supporting Information). The fluorescence spectra of both copper(I)-bound and apo-Amt1-FRET were taken by exciting the FRET donor CFP (433 nm) and recording the fluorescence intensities of the YFP (527 nm) and CFP (477 nm) emissions. An increase in FRET between YFP and CFP in Amt1-FRET in the presence of Cu+ was observed through the increase of the peak ratios (I527/I477) from 1.95 to 2.26 as soon as metal was added (Figure 1c), supporting the proposed copper(I)-binding-induced conformational change of Amt1"

Yan (p. 2): "In this paper a PMtb-based copper(I) fluorescent reporter, PMtb-FRET, was constructed by subcloning the copper(I)- binding domain of Mtb CDC 1551 (residues 1–162) between cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP), taking advantage of the copper(I)-binding induced conformation change of PMtb (Fig. 1) to determine the free concentration of the copper(I) in Mtb protein. This strategy, pioneered by Tsien and coworkers,31 33 produced a genetically encoded fluorescent reporter by inserting a sensing protein domain, which went through a conformational change upon target binding, between two fluorescent proteins that were FRET (fluorescence resonance energy transfer) pairs.31–34 PMtb-FRET was expressed in E. coli in the presence of 1.5 mM CuSO4 and purified to yield the copper(I)-bound PMtb-FRET (PMtb-FRET-Cu) (Fig. S2, ESI†). The fluorescence spectra of both PMtb-FRET-Cu and PMtb- FRET without copper(I) were taken by exciting the FRET donor CFP (433 nm) and recording the fluorescence intensities of the YFP (527 nm) and CFP (477 nm) emissions. An increase in FRET between YFP and CFP in PMtb-FRET in the presence of Cu(I) was observed through the increase of the peak ratios (I527/I477) from 2.01 to 2.45, supporting the proposed copper(I)- binding induced the conformational change of PMtb-FRET (Fig. 1)."

Or how about this swatch?

He (p. 2): "To further investigate if different metal ions interfere with the Cu+ binding, the copper(I)-binding-induced FRET changes were measured in the presence of an equal amount of other metal ions. First, the signal for other metal ions after the addition of 5 equiv of metal to Amt1-FRET was measured, followed by the addition of an equal amount of Cu+ (Figure 2b). In all cases, 100% of the signal was recovered, showing that Cu+ binding is tighter compared to that of other metal ions tested and that the presence of other metal ions does not interfere with copper(I) binding to Amt1-FRET. Also, common anions were shown not to interfere with copper(I) binding"

Yan (p. 3): "To further investigate whether different metal ions would interfere with the Cu(I) binding, the copper(I)-binding-induced FRET changes were measured in the presence of an equal amount of othermetal ions. Firstly, the signal for other metal ions after the addition of 5 equiv ofmetal to PMtb-FRET was measured, followed by the addition of an equal amount of Cu(I) (Fig. 5). In all cases, 100% of the signal was recovered, showing that Cu(I) binding was tighter compared to that of other metal ions tested and that the presence of other metal ions does not interfere with copper(I) binding..."

*Even worse? This time, the forgers couldn't even manage a citation!

I didn't have time today to cantrill the whole thing, but look forward to a lively (continuing!) debate in the Comments. Thanks again to Shawn at WPI for alerting me to the later papers.

Update (1/23/13) - Thanks also to Prof. Chris Goldsmith for the initial hat-tip on this round!

The Pterodactyl Flies Again

I'll admit it: I was a bit bummed out to read B.R.S.M.'s tweet regarding Totally Synthetic's untimely demise:

As a young pup, I cut my teeth in a few guest posts over at Paul's place. Since I saw a sexy, streamlined version of one molecule go by in Org. Lett. last week, I decided to do a (memorial? celebratory?) post in true Tot Syn style.

Folks who've read the other syntheses might agree with me that the trigonoliimines, as drawn by Tambar, resemble a terrifying pterodactyl:
Respectfully stolen from Tot Syn
Both Tambar and Movassaghi aimed for asymmetric syntheses, and started from a [2,2] fusion point between differentially-functionalized tryps. They're aiming to make the whole lot (Trig A-C), so this semi-biosynthetic approach makes sense. But Hao's latest paper sets its sights squarely on (all together now!) the (6/5/7/5/6/6) core of Trig A - sadly, a much "flatter" molecule with less 'dinosaur' character. But, the target still shows moderate antiviral activity, so the group reasons a shortened synthesis may expedite analog generation.

Hao aims to use two fairly well-known reactions to join his tryptamines: a modified Strecker, followed by a Houben-Hoesch cyclization. First, the group pops open a methoxylated, phthalamide-protected Trp precursor using CuCl under oxidative conditions (the 'cool' kids use blue LEDs now). Now they've set the stage for the really short racemic synthesis:

Initial TMS-promoted imine condensation with the aryl ketone sets up a CN alkylation, which cyclizes on the nearby formamide (probably through an isonitrile). Now here comes a 7-membered Houben-Hoesch ring closure, which they perform in a one-pot prep due to instability of the methoxy-Strecker intermediate. Basic workup, followed by hydrazine deprotection / cyclization, produces Trigonoliimine A, in a respectable 35% yield (4 steps, 3 pots).

Godspeed Dr. Docherty, wherever you are...

Update: Neil posits that Paul is still alive and well, and writing for Chemistry World.

Tuesday, January 22, 2013

Open-and-Shut Case

Dr. Shawn Burdette tweeted up the chem-blognoscenti earlier tonight to ask about some "funny business" between two papers. The first (JACS 2009, Pierre) predates the second (Chem. Eur. J. 2013, Yan) by about 4 years, and yet their "Figures 1" both look strangely, well, similar...
Well, OK, folks who play in the same sandbox sometimes use the same shovel, right? Maybe the 2013 paper became so enamored of its predecessor that it couldn't help itself.

But then, I started through the text. Since I didn't have my pink highlighter handy to cantrill them (sorry, Stu!), I decided just to clip out phrases I thought sounded Déjà vu-ish:

Pierre (p. 1): "Time-gated luminescence imaging presents an elegant solution to the problem of background luminescence by setting a time delay between the excitation pulse and the luminescence detection, thereby allowing the luminescence of the media to decay before measuring that of the probe. This technique, however, requires chemical probes with luminescence lifetimes significantly longer than that of the biological medium."

Yan (p. 1): "Time-gated luminescence imaging presents an elegant solution to the problem of background luminescence by setting a time delay between the excitation pulse and luminescence detection; this allows the luminescence of the media to decay before that of the probe is measured. However, this technique requires chemical probes with luminescence lifetimes significantly longer than that of the biological medium."

Or how about this?

Pierre (p. 2): "Notably, the observed selectivity cannot result solely from selective binding of K+ by the diaza-18-crown-6. The selectivities of the lariat ether for K+ over Na+ and Ca2+ in anhydrous alcohol are barely 5- to 10-fold.(7) Tb derivatives of these ethers also demonstrate poor selectivity (4-fold)."

Yan (p. 3): "Notably, the observed selectivity cannot result solely from selective binding of potassium(I) by the diaza-18-crown-6. The selectivities of the lariat ether for potassium(I) over sodium(I) and calcium(II) in solution are barely five- to tenfold.[16] Tb derivatives of these ethers also demonstrate poor selectivity (fourfold)."

One more for posterity:

Pierre (p. 1): "...the flexible structure of the ligand results in an overall large separation between the Tb ion and its sensitizing azaxanthone, resulting in weak Tb luminescence the aryl ether, thereby locking the complex in a conformation where the antenna is significantly closer to the Tb center. Consequently, the efficiency of energy transfer from the azaxanthone to the Tb and the resulting luminescence from the complex are increased."

Yan (buried in the Figure 1 legend!): "...The flexible structure of the ligand results in an overall large separation between the Tb center and its sensitizing antenna, BP, resulting in weak Tb luminescence [snip] The locking conformation causes the antenna to be significantly closer to the Tb center. Consequently, the efficiency of energy transfer from BP to Tb and the luminescence from the complex are increased..."

Cherry on top? The 2013 authors bury the 2009 authors' paper in Ref. 14d. Sigh.

Well, kids, I think we have our answers. While I don't have any skin in the "fluorescent K+ sensors" game, I also abhor unfair play. To this end, I've sent a cheerful email to the Editorial staff of both journals, and will print here any response I obtain.

Thanks for playing!

Update (1/23/13): CJ adds his thoughts and a pretty (damning) picture.

Monday, January 21, 2013

Traffic Cones

Well hello there, new reader avalanche! (And thanks, Nature News!)
Update: Thanks, Chemistry World!

I'm See Arr Oh, and I humbly welcome you to my tiny corner of the Internet. If you've come here looking for Blog Syn, you should probably check out my collaborators B.R.S.M., Matt, and Organometallica.

If you've got a few minutes, have a look through some JLC "classics."

I look forward to seeing you back here someday. Thanks for coming!

Friday, January 18, 2013

Friday Fun: WWWTP? CAS Stock Photo

OK, Chemical Abstracts Service, here's where I get stabby...

c. 2012, Chemical Abstracts Service

I clipped this well-meaning low-res stock photo out of a SciFinder help page. First off, what's with the incomplete PPE? Don't you suppose this enthusiastic young lady analyzes (urine?) whilst wearing gloves? She looks like she's selling glassware, BTW...I've never shown off my products quite like that.

And who are the MBA-types posing on the periphery? If they're admiring the benchwork, they should have goggles at the least! Methinks this may have been photoshopped from a med school recruiting website, perhaps?

CAS, you're part of the largest scientific society on the planet. How's about an accurate picture?


Wednesday, January 16, 2013

Blog Syn - It's ALIVE!

Remember how exciting it was back in 2009, when Paul over at Totally Synthetic posted his "NaH as an Oxidant - Liveblog," and the whole chemical community rushed to try the same reaction?

Well, we've tried to borrow a bit of that same spirit for the launch of Blog Syn, a new collaborative effort between a few chemblogosphere regulars. Go have a peek at the first post, on Fe-S cyclization reactions, and help us improve with some helpful comments.

Thanks again to my steadfast collaborators and "brothers" in chemical crowdsourcing: Matt Katcher, B.R.S.M., and Organometallica. We're on the lookout for more reactions to try, so don't hesitate to get in touch - seearroh_AT_gmail.


Tell Job With Window

A friend pointed me towards Splasho's "Up-Goer Five Text Editor." Riffing on a theme from a recent xkcd comic, it challenges users to describe their (no-doubt highly intellectual) fields using only the 1,000 most commonly-used English words.

I tried for about 10 minutes - do you know how hard it is to describe organic synthesis when you can't say "chemistry," "stir," or "product?" Here's what I came up with, at long last:
"In my job we make things from other things. When you want to get a new thing, you think a lot, get some books, and look things up. If your thing comes from rocks or trees, great! Order it. If not, try lots of bad runs, and something will eventually work out. When you get that one good run, try to make it even better. Now you can do what I do!"
Far cry from something you'd find in Scientific American, but a fun challenge nonetheless!

Readers, go have some fun, and report back: does your explanation work better?

Update (1/18/13) - The internet is an amazing place. Theo and Tom have already created the "Up-Goer Six" text editor, which evaluates your grammatical choices to tell you how far your writing deviates from "ten hundred words." Pretty colors, too!

Friday, January 11, 2013

The Sounds of Synthesis

Ever paused for a moment, standing in front of your hood, and just listened?

Labs sure are noisy places! But if you really love the "hands-on" aspect of the gig, you can't stand to walk into a lab devoid of all the onomatopoeic chatter our instruments and equipment make.

The whoooosh...pop | click! of an NMR spectrometer engulfing samples

The sci-fi whirs and sputters of fraction collectors and Biotage robot arms

The omnipresent susurrus of fume hoods and make-up air

The reassuring oily gurgle of a well-maintained high-vacuum Welch pump

The crystalline *ping*ping*ping when hot molecular sieves meet cold glassware

The unmistakable FWOMP of an imploding Dewar bath

The "shwack, shwack" noise as you put on protective gloves

"Listen! [Doo-wah-ooh] |
Do you want to hear some glassware? [Doo-wah-ooh]"
Finally, my personal favorite...high-pitched glassware harmonics. You can make these a few ways: by carefully running gloved fingers up a new pipette, slowly twisting an improperly lubed ground-glass joint, or when certain surfaces (rubber mats, wooden dowels) rub flask walls.

Happy listening!

Thursday, January 10, 2013

Friday Fun: Breakfast Chemistry

Should we tell her we don't 
call it that anymore?!? 
Source: | Laura P.
Dr. LKB, beloved chemist of the Twittersphere, just passed along a chemophobic gem from Grist. Titled "Honest junk food advertisements show you what kind of crap you're really eating" - no [sic], that's really how it reads - the post points out recent work by a Silicon Valley-based graphic designer who's equated various GRAS food additives with a vast industrial chemical conspiracy. Here's a sample:

Each "honest ad" gets a bonus eye-opening disclaimer at the bottom, revealing, gadzooks! - snippets cribbed directly from respective Wikipedia pages.

Well, two can play this game! Let me tell you about my standard breakfast...
Every morning, I go downstairs to brew up a harsh brown slurry of stimulants, sterols, and terpenes (I usually take it with some aspartame / maltodextrin, thanks!). 
When my stomach grumbles, I reach for a 6-pack of whole wheat toroids, chock-full of gums, algin, sorbic acid, and sodium chloride. After 50 seconds of resistor-charring, I spread microbially-enhanced whey-milkfat composite all over it, ideally while it's still warm. 
Sometimes I'll wash this all down with a fiber-filled suspension of cellulose oligomers, ascorbic acid, and fructose. Yum!
[Sigh]. Chemists, how do you do mornings?

Molecular Machine, Unadorned

So, chemists, you've probably seen this article over at Nature News, which reports a "molecular robot" capable of traveling down a track to assemble a small peptide. Pretty awesome, right?

Source: Nature News | Leigh Group, University of Manchester
Now, that's a cute cartoon, but what's behind the scenes? Intrigued, I hustled over to Prof. Leigh's Supporting Information, and found the real gizmo, spectra and all. Take a look!

Source: Science | Prof. David Leigh
(Yes, that's a carbon NMR, for a single compound.)

I will never complain about characterizing small-molecule drugs again!

Wednesday, January 9, 2013

A "Novel" Concept

A provocative story by Megan Garber in The Atlantic indicated that, as a society, we expend significant effort on a specific written pursuit - email - that few of us ever get to see in its entirety: " audience of one" (you!).

"Eureka! I shall compile all my email
and sell it for $19.95 + tax!"
Source: NBC / Free Library of Philadelphia
One conservative estimate from a personal help app averages annual 'Sent' words at 41,638 - which, assuming 250 words / page, equates roughly to several short novels such as The Old Man and the Sea. Well, I thought, how might that apply to a bench chemist / blogger?

First, I counted up emails sent from all accounts: one work account, one personal, and one pseudonymous. Total messages sent in 2012? 1,904.

Next, I concocted a reasonable estimate of words per email - yes, I counted words in about 20 different emails, and arrived at a figure of ~100 words / personal email*, and ~64 / work email. Total words sent in 2012? 148,784. But wait, there's more! I also wrote several grant proposals last year (~20,000 words), and 230 blog posts (~200 words apiece, or 46,000, not counting drafts or notes here). For the coup de grace, I thought I'd include my scientific notebooks, which (OK, not typed) still take up quite a bit of mental energy. In 2012, ~160 words x 402 pages = 64,320!

Sum the bold numbers, and you get 279,104 words. That's 1,116 pages of my potential "Great American novel," pushed annually into unseen folders.

Now you may say that sounds utterly ridiculous or far-fetched. But does it? Remember, I've only mentioned a few different avenues for the written word - I haven't included text messages, tweets (4,000 last year), paper drafts, handwritten notes taken during seminars and meetings, or simple notes scrawled on Post-Its around the office. Yes, it's likely that Derek, Paul, Adam, CJ, Ash, BRSM, David, Mitch, Carmen, or Vinylogous each writes an equivalent of Lord of the Rings - the whole trilogy - each year in aggregate.

*For the critics: I did take into account that some sent emails read simply "Make it so" or "Be there Friday." Contrast that with multi-paragraph emails I write to Editors, local gov't reps, and family members, and you probably strike a balance. Still doubtful? Just remember that 90% of all statistics are made up 'on the spot' : p

Tuesday, January 8, 2013

Grad School's Mental Toll

There's a moment during your first panic attack when you're absolutely certain you're going to die.

Kermit does his "chem grad student"
Source: mlkshk Tumblr
A 'perfect storm' of sorts arose during my fourth year in grad school. A failed blood donation, where I passed out and couldn't get back up; chalked up to lack of sleep. Or waking up with horrific nightmares after just a few hours; too much coffee, maybe?

At the time, I would wake up at 6:00AM to take the first bus into campus, fortified by a "breakfast" of junk food and soda. I'd work 5 hours, eat a frozen microwave meal, work 6-8 more hours, then stumble home for a burger and a beer. Between coffees and colas, I was averaging seven caffeinated drinks per day. I developed facial tics, put on weight, and felt chronically ill.

Now, sprinkle in some "life events." A building move. A group switch. A death in the family. A sudden, out-of-the-blue contact from a long-forgotten relative. Financial woes. Managing an undergrad. Writing an ORP, two papers, and fellowship applications at the same time (not recommended). All occurred in about 3 months, around the holidays.

I distinctly recall the first time I felt creeping doom: I was driving back to lab after dinner, and my vision blurred. My heart began to race, and I felt trapped in my own car. Luckily, I had the presence of mind to pull over, and after about five minutes the symptoms subsided. So. . . I drove to work, anyway. Ugh.

A few weeks later, more bad news: a potential postdoctoral gig fell through, with no replacement in the wings. The economy seemed headed ever further downwards; no one got jobs. My lab work had stalled, with a few (small) fires to boot.

One evening, I got up from the dinner table after a long discussion with my S.O. and realized, quite suddenly, that I couldn't walk. I lowered myself to the ground, heart thumping, knees wobbly, a rush of grey spots clouding my eyes. I began seeing darkness. That's it, I thought. That's how it ends.

I laid there for some time, writhing. I tried to sit up, but couldn't. When I could finally stand, we went immediately to the ER - not covered under student insurance, btw. I spent the night hooked up to a EKG, and was advised to seek counseling in the next week.

What followed was completely new to me: Group sessions. Medication. Crisis intervention. It took me several months to get back to normal working hours. I felt trapped in seminars, and took seats near the exit. I didn't drive much. Every few days I'd have short spells like the initial attack, but never as serious. I suppose I was lucky.

It was time to completely redo my life. I reduced my working hours. I took walks, and started routinely exercising again. I ate healthy breakfasts and forced myself to take extra vegetables and fruits. I wrote letters and long emails. I began a renewed effort to look ahead, and didn't dwell on the present. I made time for myself every day. I prayed.

Things got better with each progressive year. I defended. I lined up a postdoc. I got a job after a lengthy search process. Luckily, I had a loved one with a "real job" to help me. I don't wish to consider what it would have been like to go it alone.

Grad students: if you feel like you can't take it anymore, or don't feel like yourself, seek help! Don't feel stigmatized, and don't hesitate. Certain decisions can't be taken back. Always have someone to confide in, and always make time for yourself, even if it's ten minutes a day.

There's a lot more life to be lived on the other side of grad school.


Note: I wrote this as a response to Chemjobber and Vinylogous Aldol's "Grad School Mental Health" discussion. For more posts in the series, check out their sites.

Bytesize Science: Day-Glo Tour

Glass-lined reactors? Particle dispersion? 'Blaze' Orange? Soft jazz?
Count me in!

Bytesize Science, an outreach offshoot of the ACS, produced this video, which takes you on a 7-minute tour of the brightly-colored Cleveland-based Day-Glo corp (Slogan: "Color. Only Better.")

If you've ever wondered why process chemists need to consult with plant engineers about "pipes and tubes" all the time, this video will clear that right up. My favorite quote (6:40), which takes place in front of a 5,000-gallon reactor:
"Y'know, the dye industry isn't like the pharmaceutical industry [where] everything has to be pure and cutting-edge. We need a pot, and we need to heat it." 
Have a look, and let the ACS know what you think!

Credit due to Reddit Chemistry, where I first saw this posted.

Monday, January 7, 2013

What-a-Ouabagenin! Grams on Demand

I can't believe I got back from New Year's without finding a single post on ouabagenin* [wah-bah-jenn-in], the latest from Phil & Co. in Science this past week:

Ouabagenin, a polyhydroxylated (>5 -OH groups) cardenolide (steroid with an appended lactone) positive inotrope (helps heart pump more forcefully) had been completed only once before, in a 40+ step relay synthesis by Deslongchamps in 2008 (got all that?!?). Only a few mg were prepared, and those of you familiar with the Baran group know that the only real way to make natural products is with a shovel and bucket - gram-scale, baby!

Hulkster - Quite interested in
gram-scale ouabagenin precursors...
So, we start out with 20 g of cortisone acetate - just one reduction shy of Preparation H - and two steps later have a fully protected version of adrenosterone. The group first tries a porphyrin-catalyzed C(19) hydroxylation (the bottom-left methyl), which doesn't work, so they opt instead for some fancy solid-state photochem to generate a cyclobutane ring, which selectively pops open with NIS under sunlamp irradiation.

Selective de-ketalization and iodide hydrolysis sets the stage for a three-step sequence (peroxide, SeO2, peroxide) to generate a diepoxide (right, top), a.k.a. the "most difficult transformation to secure on scale." They toss a "gamut of conditions" at the molecule, only to receive mixtures of enones. Finally, they find that using in situ Al-Hg amalgam (we're talking foil / scissors here!) combined with Sharpless "on water" suspension produces the desired triol, which they wrap up as an acetonide.

Next, "superhydride" reduction both reduces the ketone and protects - as a boronic ester - the remaining two hydroxyl groups. A little Saegusa-esque dehydrogenation, a fluorous solvent-enabled bond migration, and a Co-catalyzed hydration produces 'protected ouabageninone' (right, bottom).

Endgame - We're not out of the woods yet, folks! Conversion of that lone ketone into the vinyl iodide (hydrazine, iodine, TEA) followed by a modified Stille returns a butenolide diene. They again toss in a 'kitchen sinkful' of reductants, only to find that dicobalt-borane (cool!) followed by Barton's base (N-tert-Bu-TMG) produces the correct butenolide orientation (3:1 dr). A touch of HCl in methanol liberates the natural product.

Despite the fact that they report the last few steps on just 30-60 mg, the group claims that they have >0.5 g parked at the protected ouabageninone (vide supra). With this synthesis, Baran also alludes to the overall usefulness of his "redox-relay" strategy, which has certainly served him well before.

*Bonus - In the Scripps press release, Phil calls ouabagenin "probably the most polyhydroxylated steroid known on planet Earth." Billions of yet-undiscovered microorganisms could not be reached for comment.

Escalation: Authors Respond

Regular readers know I sent out an inquiry to the Fe-S authors a few days back:

Dear Prof. Nguyen:

Good afternoon. My name is See Arr Oh (a pseudonym), and I write a chemistry blog called Just Like Cooking. I've posted about one of your recent publications in JACS ASAP:

Another chemist at Princeton graciously offered to repeat one of your reactions (Table 2, entry 2), and could not duplicate your group's yield or purity. Further discussion can be found in the comments section of the second post. Additionally several other members of the chemistry community have expressed an interest in running it themselves, with the intention of aggregating data under the Twitter hashtag #RealTimeChem.

Please share some more information - do you have any hints or tips for successful duplication? 

Thank you in advance,
See Arr Oh

Unfortunately, my spam filter ate the (prompt) response, and thus I'm posting it a few days later than when I received it back on 1/2/13:

Dear See Arr Oh,

Thank you for your mail. First, you should carry out the reaction in the same scale as described, otherwise, sulfur is comsumed by reacting with methylhetarene before combining with iron. Second, a vigorous stirring is necessary to disperse iron powder into the reaction mixture. At this temperature, the reaction mixture is homogeneous except iron powder. Third, the reaction should be carried out under Ar atmosphere because oxygen is not an innocent impurity. Oxygen in the reaction tube is best removed in vacuo (10 mmHg is ok) then the tube is filled with Ar. This cycle is repeated twice. Before running an NMR spectrum of the crude mixture, paramagnetic iron residue should be removed by syringe filtration to avoid any magnetic pertubation. In most cases, the products were formed as black solid. The prduct is fluorescent with UV lamp.



Interesting tidbits: vigorous stirring, as opposed to a debate in the comments over whether we should stir the reaction at all, scalability issues, and recommendations for NMR analysis - Fe junk really does mess that up!

Methinks this advice might come too late* for anyone trying the reaction today; sorry, B.R.S.M.!

*Addendum - That's a lot of "insider info" in that email, and I'd argue a lot of the online discussion we've had on this reaction could have been avoided by a more complete Supporting Information file. None of that info was available either there or in the paper, nearest I can tell. Readers?

Sunday, January 6, 2013

Turning Wishes into Horses

A fantastic summary crossed my desk today, courtesy of the RSC's Chemistry World. It profiled a new reaction from the Milstein group, just reported in Nat. Chem., that just looked so tempting: oxidation of a primary alcohol, using water as the "O" source, with hydrogen gas as the lone byproduct.*

And thus began what my brain usually does, "Science Wish Syndrome." Not familiar? Here's the stages:

1. Unbridled Enthusiasm - "Holy cow, that reaction looks fantastic! I'm sure it will produce 20 new analogues / help me wrap up my thesis early / solve world hunger. I can't wait to try it!"

2. Skepticism / Doubt - "Well, Blogger X tried it, and couldn't reproduce the yields. And the Supporting Info says it only works with 100 mesh hyper-refined silver powder sourced from Argentina. Still, it's in Nature / Science / JACS / Angew Chem, so it must work, right?"

3. Despair - "I ordered all the reagents, and used my last 0.3 mg of shootmenowicene in the test reaction. I barely got 10%, and it's a mixture of stereoisomers! Who the heck let this into this journal?"

Readers, does this ever happen to you? Modern chemistry publication, with ASAP format, DOI codes, PDB uploads, and overall rush to publish before the guy on the other side of the pond, seems forced somehow, and doesn't always live up to the glowing reviews crowed about in press releases.

Over at Not the Lab, Vinylogous has suggested that we compile a sort of post-hoc online review journal, playfully named "Blog Syn" (after 800-lb-gorilla-in-the-room-for-synthetic-methods Org. Syn.).

Well, how might something like this work? I'd assume that the community would have some sort of mechanism to suggest papers, say, for when too-good-to-be-true chemistry like the NaH 'oxidation' comes 'round. A central aggregation point, perhaps cultivated by an "Editor / Blogger" would then issue requests for duplication. To ensure results were processed in a timely fashion, a deadline would be suggested (2 weeks?) and the "Duplicators" would have to authenticate that they tried to cleave to the original conditions as best they could. A digital "Stamp of Approval" might then follow the reaction through the online world, indicating, much like Org. Syn., that the reaction works in others' hands.

Readers, would anyone like to be part of such an effort? Methinks the #RealTimeChem crowd could get excited about this. Yes, I know everyone's busy, and this isn't the first thing you think of when there are proposals to write, classes to teach, or conferences to attend. But the literature will only be as good (or as bad) as the folks who contribute, and we desperately need more quality control.

*Update - It occurred to me (too late!) that I sound like I'm condemning the Milstein reaction, which I have not tried, and have no reason to suspect won't work as of this writing. I just wanted to use it as a backdrop for seemingly "perfect" reactions that end up not living up to expectations. The reaction, as reported, needs some scope exploration, so only time will tell if it's as widely applicable as I'd hoped.

Saturday, January 5, 2013

WWWTP? "Unjunked" Candy

While shopping in Target (Tar-ZHAY) earlier tonight, some food in eye-popping purple & black wrappers caught my eye. UNREAL markets so-called "unjunked" candy, which contains "no corn syrup, GMOs, or artificial flavors." Naturally, I bought one ($0.89, not too shabby) and I can report that it tasted just like the intended Snickers bar facsimile.

But here's the rub: a list on the back (see picture) proudly displays corporate commitment to "chemical-free" - by transforming a bunch of scientific adjectives into pseudo-plural nouns. What, may I ask, is a single "hydrogenated?" Would you say "No Crafts" if your fridge were devoid of craft beer?

The 'organic' ingredients they've constructed the candy from include:
Milk chocolate (cane sugar, chocolate, cocoa butter, milk powder, organic blue agave inulin, skim milk, soy lecithin, vanilla extract), caramel (tapioca syrup, cane sugar, fructan (prebiotic fiber), organic palm kernel oil, whey, milk protein concentrate, organic cream, vanilla extract, salt, soy lecithin), peanuts, tapioca syrup, cane sugar, organic palm kernel oil, skim milk, peanut flour, salt, hydrolyzed milk protein, evaporated cane syrup, soy lecithin
Inulin? Fructan? New to me. Turns out both are fructose-based dietary fibers, which in this context replace some of the fats and sugars found in similar candy bars. However, these soluble fibers often aren't well-tolerated intestinally, similar to known gut troublemakers sorbitol, maltitol, or lactose. My current stomach ache indicates I might be susceptible; please think on my sacrifice when the Pulitzers go out next year...

P.S. I'm no marketing whiz, but "Unreal?" If unable = not able, and unclear = not clear, doesn't 'unreal' = not real? For a candy bar made without "artificial" ingredients? I think the intended sarcasm might be lost on the way to the checkout.

Wednesday, January 2, 2013

Christmas Chemistry Cornucopia

Here's a few things I unwrapped this past week:

I'm very lucky to have such understanding friends and family.


Dr. Sonja Krane, Managing Editor at JACS, contacted me to encourage dialogue with the authors of the Fe-S redox catalysis paper. In the interest of full disclosure, I've reprinted my email to the lead author, and I will re-post any response I receive.

Dear Prof. Nguyen:

Good afternoon. My name is See Arr Oh (a pseudonym), and I write a chemistry blog called Just Like Cooking. I've posted about one of your recent publications in JACS ASAP:

Another chemist at Princeton graciously offered to repeat one of your reactions (Table 2, entry 2), and could not duplicate your group's yield or purity. Further discussion can be found in the comments section of the second post. Additionally several other members of the chemistry community have expressed an interest in running it themselves, with the intention of aggregating data under the Twitter hashtag #RealTimeChem.

Please share some more information - do you have any hints or tips for successful duplication? 

Thank you in advance,
See Arr Oh

Cross your fingers!