New Rainbow of Synthetic Firefly 'Fire'

I love deep answers to seemingly simple questions, like why grass looks green (emission spectra), or what causes "metal" smell (hand oils). I also enjoy rational drug design, the process where a hit becomes a lead through a series of well-thought and "why not?" changes. Finally, everyone likes flashy colors, especially natural ones.

Well, what if a recent paper met all three criteria? And had a catchy abstract graphic, to boot?

Look no further than the latest Angewandte Highlight, out now in the Early View section. Prof. Wei Guo and his students sum up progress towards synthetic luciferins, which are capable of bioluminescence just like the yellow-green D-luciferin many of us remember from childhood firefly collections (I'm hardly the first blogger to mention synthetic luciferins, btw. See Scheme 1 in the paper for a general luciferase reaction).

Credit: Guo et. al., ACIEE Early View

Regarding design, the chemical ground rules have been known since the late '60s:

1. Don't mess around too much with the phenol group. It prefers to be -OH or -NHR.
2. Heteroatom swaps in the two heterocyclic rings are mostly OK.
3. Don't cleave the carboxylate, or you'll turn out the light!

With these simple statements in mind, chemists have brought forth a slew of new luciferins over the past decade. The take-home message? Depending on the substitution pattern, luciferase lights up over a broad range, from deep in the red (>600 nm) up to bright blue (around 460 nm). Researchers use the new luminescers as probes, guest-starring in cellular assays sometimes reserved for the mighty GFP.

A few things caught me by surprise. First, how such tiny structural manipulations could produce such large changes to the observed bioluminescence - an S-for-Se swap gains 50 nm (red shift) whereas an S-for-N-Me buys you 100 nm...in the opposite direction! (blue shift) Second, I had no idea that there was a mutant version of luciferase - ULTRA-GLO - that not only permits high-throughput analysis, but also increases the observed light 3- to 6-fold, like a wild molecular highlighter.

"Pure Goodness" - Whirlpool's Chemophobic Water Ad

Last night, courtesy of Chemjobber, came this ridiculous sham ad interesting tidbit:

Here's the Whirlpool pop-up ad I saw that started it all: "Don't drink from the periodic table." #chemophobia http://t.co/M5MBCiKf

Done chuckling yet? I hope not, because you haven't seen the accompanying video, with cloying tagline "Pure Goodness." Apparently, for Whirlpool's target market - wealthy American moms with stupendously huge kitchens - the issue of anything in drinking water scares them silly. And that's the right word, because that pop-up ad above literally reads "don't Drink from the periodic table." Did I somehow miss the memo?

News Flash! Dateline: July 30, 2012 - Water officially no longer derived from hydrogen, oxygen; sources say it exists in new 'drink dimension,' far removed from natural world!

OK, I get it: filtering water removes certain trace metals and organic products you might not want to ordinarily consume - for the moment, we'll overlook fluoride, sodium salts, or relatively innocuous trace metals like iron and copper. If you believe the ad, every poured cup of tap water contains the following (~ 0:09 in the video): mercury, chlorine, lead, ethylbenzene, ortho-dichlorobenzene, lindane, atrazine, para-dichlorobenzene, endrin, MTBE, and benzene. Nevermind that two of the listed pesticides (lindane, endrin) are long-since banned from food crops, or that local water authorities test for most of the other potential contaminants.

What about those scary-looking chemical structures at 0:05? (see left). I checked 'em out: from left, moving clockwise, you have carbofuran, dinoseb, and alachlor (Picky pedagogical note: I've never seen a gem-dimethyl group drawn that way before...should I expect some sort of agostic bond?). Dinoseb and carbofuran are both banned pesticides, and alachlor, though common, lists as only a Class III (slightly toxic) toxin.

As with all chemophobic ads, realize that Whirlpool exaggerates the situation to sell more fancy refrigerators. The same effect can be achieved with any carbon filter: remember Pur, or Brita? Perhaps then you wouldn't have to worry about the other pressing concern (0:58)...


...deadly fridge fungus!

"Everyone run, it's got Timmy!"
Credit: whirlpool YouTube

Great Expectations for 'Metal-Free' Reactions

Reading through some recent "metal-free" coupling literature, I came across a fantastic footnote. Check out the lengths chemists Carsten Bolm and Isabelle Thomé have to go to in order to certify their latest reaction:

"(16) Great care was taken to avoid the presence of transition metal impurities. All starting materials were synthesized without using any transition metal...reagent transfers were performed with one-way plastic spatulas, and new glassware and stirbars were used for the cyclization reactions. The starting materials and reagents were analyzed to the detection limit of 4 ppb by atomic absorption spectroscopy (AAS) or inductively coupled mass spectrometry (ICP-MS).

Data [for a representative intermediate] - Cu < 4ppb, Pd <4 ppb; Kcarb - Cu < 4 ppb, Pd < 4 ppb; DMEDA [ligand] - Cu 2.4 ppm, Pd < 4 ppb." [Emphasis mine]

Sand - Probably > 4ppb "active" metals!
Source: 123RF

Wow. 


I'll be honest with you, I've never tested for metals in my starting materials below ~1 ppm (Food for thought: here's an EMA document detailing allowable catalyst residue in human medicines).  I'd wager that 99.9% of workaday bench chemists haven't, either. 


Bolm's group endures this rigor because, well, they literally wrote the book on trace metal catalysis. Quite honestly, I'd bet that they felt a bit uneasy when they measured the DMEDA copper concentration; more than a few of these "metal-free" reactions proceed with vanishingly small amounts of catalyst.

Now Where Have I Heard This Before?

Yesterday morning, I heard an NPR report that detailed more strife in a typically white-collar profession. Whose field do you suppose we're discussing?

"...schools routinely said that 90 percent or more of their graduates had jobs nine months after graduation. It turns out they were including barista positions, low-level marketing gigs, or just about anything else you could call a job." [Emphasis mine]

"At some schools, less than a third of their graduating class were obtaining long-term, full-time jobs" 

"A new study reveals that since 2009, the median starting salary...has fallen 35 percent." 

Any more of these posts, and I might
have to rename the blog!
Credit: Arrested Development

Give up? It's not chemists, it's lawyers (This story does seem to spring eternal, given earlier posts by Chemjobber and myself). The comparison's just too apt to pass up: young grads consider financial security, invest their time towards an advanced degree, and later awaken to an economy facing a glut of overeducated professionals.

To their credit, at least the American Bar Association (ABA) seems aware of the risk, and wants to inform newly-admitted legal students of the economic dangers. Their Nero, unlike ours, isn't fiddling while Rome burns. So, what lessons could Ph.D.-granting chemistry departments learn from the legal profession? 


Honesty - Brian Vastag's Washington Post article from two weeks ago really struck a chord, amassing nearly 3700 comments and prompting discussion up and down the blogosphere. Although it's a political talking point (STEM STEM STEM!), chemical graduate departments must take a page from the ABA and inform new recruits that the salad days of secure scientific employment have passed.

Transparency - As Janet Stemwedel recently mused: What does a chemistry Ph.D. get you? Are alternative careers really playing out? How are pharma salaries adjusting to the recession? Are stock options, benefits, or retirement plans really going away? Where will the jobs be in 10 years?

CJ's correct to call for career tracking; after all, we have the technology! Through a combination of email surveys, social network mining, digital IDs, online CVs, and employer reporting, we should be able to paint a more complete picture of the sci-employment landscape. Using data from past students, new grads could adequately prepare themselves, and younger students could better assess their decision to attend grad school.

Curious Collaborations

Tried telecommuting? It's tough when you're bench-bound, since you can't really catalyze by cell phone, or take HPLC by HTTP. Of course, research takes strange twists and turns all the time: witness the schism between compound "designers" and "makers" in Pfizer's geographically divided new organization. 

Long-distance scientific collaboration crops up in all sorts of interesting places. Creative minds always find a way, albeit leaning heavily on technology to help smooth things out. Here's a few interesting examples:

Physics by Ham Radio (1950) - While on sabbatical in Brazil, Richard Feynman continued his Caltech research by hooking up with a pirate ham radio operator.

"I found an amateur radio operator in Brazil, [but] because there was something slightly illegal about it, he'd give me some call letters...So I'd say 'This is WKWX. Could you please tell me the spacing between the certain levels in boron we talked about last week?"

Source:Brian Dettmer, 2008
Thanks to Chemjobber for pointing this out!

Manuscript Writing by Phone, Post, and Boat (1969) -  Writing in How the Hippies Saved Physics (p. 47), author David Kaiser describes how two authors - Abner Shimony and John Clauser - tackled paper submissions from afar. While writing their first quantum mechanics manuscript, Clauser decided to sail down the East coast, towards an eventual postdoc at Berkeley. Here's how it went:

" ...each time Clauser sailed into a port along the East Coast, he would find a telephone and check in with Shimony...then Shimony would mail copies of the edited draft to every marina in the next city on Clauser's itinerary, 'some of which I picked up,' Clauser explained, "and some of which are probably still waiting there for all I know.'"

SPARC (1992) - The Space Physics and Aeronomy Research Collaboratory, first established at the University of Michigan, grew over the next 6 years to include several worldwide radio telescopes. The project now incorporates behavioral scientists, computer programmers, physicists, and astronomers, who "...sit down to their computers in the comfort of their offices and call up a screen that allows them to control and gather data from more than a dozen instruments located around--and above--the globe." Online collaborative tools developed by this consortium include Java programs, chat rooms, and a digital whiteboard.


Instant Messaging, Liveblogging, Wikis (mid-2000s) - Regular readers recall the recent uptick in live-blogging, that is, conducting a live experiment while posting data, observations, and commentary. Paul at Tot Syn famously debunked NaH oxidation, and Azmanam proved that LemiShine cleaner contains citric acid. The open science movement brings together scientists from around the globe to live-edit papers on electronic documents called wikis. My biggest surprise? Digging up an IEEE abstract on eChemIM. Apparently, it's a real-time application that allows exchange of structures and protein sequences through a simple pop-up window. Sounds like a cool new way to collaborate!


Readers, have I left out your favorite way to connect? Let me know in the comments.

JLC Turns One!

Alitta virens (sandworm)
Credit: A. Semenov, White Sea Biological Station

Heartfelt thanks go out to each and every person who clicked over here in the past 366 days (leap year!).

No new post today; I'm going to take the day off to celebrate. How does one celebrate a blog's birthday? Maybe an ice cream cone with a candle stuck in the top, or a cupcake with a sparkler?

Here's a few salient factoids from my first year "full-time."

Year One Stats:
Total Pageviews: 74,000+
Total Posts: 125
Tweets: 3,414
Blog Carnivals: 2

Total Time Blogging: 500 h, ~6% of the last year.

Posts Elsewhere*: The Haystack (26), Chemistry Blog (4),  Chemjobber (3), Totally Synthetic (2), Sci Am (2), Newscripts (2). 
(*May 2011 - July 2012. Want a guest post, or want to guest post? Email me at seearroh_AT_gmail_DOT_com)

Recurring Themes: Chemophobia, Skepticism, Cartoons, Space Dinos, Arsenic Life, Structure Mishaps, Food Chemistry, Catalysis, Pop Culture Chemistry, Blog Philosophy, Arts & Crafts

Friday Fun - WWWTP, Cartoons!

Anyone out there watch Adventure Time? The animated show, currently airing on Cartoon Network, follows the adventures of a boy and his talking dog in the magical Land of Ooo.

(Bear with me, I've only seen this episode)

Source: Cartoon Network

While flipping through the channels, I happened to land on a rather new episode, called "Goliad." It involves one of the main characters - a synthetic biologist? - spawning a giant pink Sphinx from a mixture of DNA, 'chemicals,' chalk dust, and an old tooth. But that's not what caught my eye: check out the prop chalkboards set up in the "lab" - those are resonance structures on there!

(Ironically, though the characters understand electron movement for the carbonate anion, and can apparently clone life forms, the resonance structure for benzene escapes them. But, hey, this adventure occurs in a castle shaped like a wedding cake, so...caveat lector)

Everything's bigger in Texas.

One tiny problem: this chemistry know-how seems to disappear between takes. Here's another clip from the same episode, where the previously-correct carbonate has mysteriously grown another bond.

Most kids watching this will just gloss over it, assuming some mad-scientist gobbledygook. But, those of us in the WWWTP camp just can't help ourselves.

Happy Friday! Go watch some (scientifically accurate) cartoons!