Molecular Chords - A Musical Periodic Table

"One day, my system will be used
to categorize cupcakes, texts, and
crooked politicians."

Dmitri Mendeleev had a good thing going. Not only did his periodic table allow him to predict the properties of "missing" elements, it also provided a future template for all sorts of pop-culture catalogues - from beer and QR codes, to chocolate and shoes. Even the universe has one! If you want to get really meta, there's even an online collection (wait for it...) a periodic table of periodic tables.


While researching an upcoming post, I encountered a few 'Periodic Tables of Music.' Here's one for jazz, and another for pop music. But what about a table where the atoms themselves compose the music?

Enter Mahadev Kumbar, an Adjunct Professor at Nassau Community College in New Jersey. I found his Musical Periodic Table in a 2007 article and associated lecture series written for the Journal of Chemical Education.

From his introduction:

"One (perhaps surprising) aspect of the natural world is that each and every process in nature—chemical or otherwise—produces some kind of sound, whether audible (20 Hz–20 kHz) or nonaudible (<0 Hz and >20 kHz), characteristic of that process. Those sounds, I believe, are the music that is the universal language of the natural world."

To construct his table, Kumbar grabbed a few lines from each element's emission spectrum. He then mathematically transformed the energies of elemental electronic transitions into characteristic notes played by each atom. 


Kumbar also notes that "atoms...clustered together...tend to generate unique and distinct music." Perhaps each element could be considered a player in a nanoscale symphony: for instance, silver bromide (AgBr) plays a beautiful open third (C6-E6), while bleach (sodium hypochlorite, NaOCl) plays more of an inverted C#min chord, stretched across three octaves (E5-G6-C#7).

Schools = Summer Space for Small Companies?

Ahhh, summer! Time to put your feet up, barbecue, maybe take a long vacation with the family. But while you're away...who's working in your lab space?

"Piled Higher and Deeper" by Jorge Cham - www.phdcomics.com

Long-time readers know I work at a fairly small biotech; we've joked before over whether to call ourselves "micro" or "nano" based solely on full-time employees. Due to our infrastructure limitations, we depend on local universities and off-site collaborations to move projects along. Sometimes, small companies like us will band together in an incubator facility (examples: Seattle, Virginia, Mass), with room to work out their science, and (presumably) access to shared instruments like NMR, MS, or HPLC.

Critical lab equipment

A recent visit to our local Uni revealed another potential angle: unused academic lab space. Despite rumors to the contrary regarding crazy hours grad students work, repeat trips have taught me that this particular school doesn't seem too strict about summer schedules. Perfect storm, right? Here's some fully-functional labs waiting for someone to use them in a down cycle. The staff's there, safety's looked after, police and fire standing by, what more could you want?

I'm certain I'm not the first to voice this idea (examples: UT, Iowa State). I'm sure there's boondoggles to work out with IP transfer and inventorship. But I'm surprised I don't see more universities opening their doors to entrepreneurs full-tilt over the summer months.

Mushroom Pharmacology...as seen in USA Today!

'Magic' Mushroom G. lucidum
Credit: Wikipedia user Eric Steinert

While peering through the evening's Twitter foliage, I spotted a fungal gem among the fallen, matted links of my "social media ecosystem." Following the trail blazed by Matt Herper and Shrikant Manti, I hiked over to USA Today's ScienceFair blog to read "Chinese 'mushroom of immortality' genome mapped," by Dan Vergano. Great title, but what about the post itself?

Vergano explores the recently-reported genome of the lingzhi / reishi mushroom (G. lucidum), an Asian traditional medicine with a rich pharmacopoeia. The reader gets a brief summary, slightly sparse and unstructured - note the oft-used hook "the study authors note," a sure sign that we're venturing into uneasy territory - and a few throwaway terms, like "Triterpenoids" [sic] and "more than 12,600 genes" (that's a mighty round number for any organism, I'd say...). The piece feels strangely unfinished, like it lost all its momentum after the initial burst from a catchy headline.

Laccase 'lights up' lignins!
Source: Mashed-up from Zeeco and U-Maine

So, it's off to Nature Communications for a more thorough look at the item of interest. Sure enough, looks like the bulk of the USA Today post simply paraphrases the opening paragraph of the manuscript! From mentioning "400 compounds" to a passing remark about biofuel production, it's all there. But where did the strange '12,600' value come from? We'll turn things over to lead authors Chen, Xu, and Liu: Table 1 states that the G. lucidum genome contains 16,113 protein-coding genes, and further down (Fig. 2b), a Venn diagram shows that 12,646 genes are expressed throughout the fungus' life cycle. Now we're getting somewhere! The authors go on to discuss bioactive polysaccharides, mysteriously absent from the post, and then the variety of -ases that contribute to the 'enzymatic combustion' of wood lignins...the best quotes are always buried!

He knows fungal gene mapping
Source: KT5 blog

Instead of heaping on further criticism, let's fill in some blanks here. Triterpenoids aren't so much individual compounds as a family affair - the catch-all term refers to any compound produced by stitching together six isoprenes, a small 5-carbon synthon common to all plant life. Perhaps you've seen lots of triterpenoids without recognizing them: lanosterol, the precursor to human sex hormones testosterone and estrogen, falls into this class. If you're more chemical biology-inclined, check out the Discussion, where the authors use gene sequence and mapping technologies - SMURF, anyone? - to predict zinc-finger nuclease clusters, and then discuss the secondary metabolites arising from a wide variety of expressed cytochrome P450 (CYP) enzymes, the original biochemical bandits behind selective C-H oxidation. 

(P.S. - This mushroom really represents in the primary literature: a search for the term "lucidum" only brought up 140 hits at ACS, but this ballooned to 2,955 at Wiley, and 5,000+ at ScienceDirect!)

Art Antics

In case you hadn't heard, B.R.S.M. is running a pictorial carnival of sorts. His angle? To celebrate the upcoming 66th birthday of venerable chemist - and serial "chemical artist" - K.C. Nicolaou. In keeping with the spirit of the game, we were asked to limit our artistic efforts to the same five molecules. Shown below are my (admittedly ridiculous) entries. 

Vancomycin: Profiles, Pathways, and Space Monsters
(with apologies to Jeff Seeman)

Really, it's what I'd always expected to see published...
(The mustache substitutes for the bridging isopropylidene!)

Help for a Filmmaker - What's Your Lab Like?

Good evening, chemists everywhere! I've recently received an email from a gentleman interested in writing screenplays about organic chemists (Finally! What took so long???)

I've extracted a few of his remarks, below.

"...I'm an independent filmmaker currently working on the first draft of a screenplay. The story is essentially about two pharmaceutical researchers...I could easily invent what I imagine the laboratory environment is like, but I think [I'm] simply rehashing tired stereotypes." 

"What I want is a level of realism that respects the science and presents it in an honest way...I have a couple of questions about life in the lab (do you listen to music, what are supervisors like?, etc)."

(Like any good pharmaceutical researcher, I'm looking to 'outsource' my answer to all of you!)

Ideas? Comments? Anyone want to describe their lab environs? Any cool things you'd always wished would be on camera - bright neon-orange crystals, towers of foam, metallic mirrors? Have any fun scientific toys? (flow reactors, robots, lasers...).

I hope to collect your responses, along with my own, and toss the whole bundle his way. Any help you can offer would be greatly appreciated.

See you in Hollywood! (or at least direct-to-DVD...)

Trending Up

I've been pleased to see blog traffic picking up in the past few months (Thanks!).

For those unfamiliar, most blog toolkits show graphical representations of hits against time, so you can tell when certain posts gain readership by distinct "blips" on the trendline. The chemblogosphere has coined several punny, tongue-in-cheek epithets for increases that result from specific sites. Here's a few I've heard bandied about:

Reader Submission: Found Chemistry,
Hendersonville, NC

The "Lowe Lift"
The "ChemBark Crush"
The "Chemjobber Jump"
The "Slate Slam"
The "Reddit Rise"
The "Bora Bump"
The "Zimmer Zing"

With my pithy phrasing cap on, may I suggest a few more?

The "Wavefunction Wobble"
The "B.R.S.M. Blast"
The "CENtral Science Cuddle"
The "TotSyn Trifle"

Readers, have I missed any?

Adventures in Publication: Malaria Sandwich

Hot on the heels of the recent ferrocene-based carbonic anhydrase inhibitors (see Pipeline or Chemistry Blog for more perspective) comes a few more medicinally-inclined sandwich compounds. Published in back to back ASAPs, the new leads stitch together an antimalarial quinoline and a glycoside with some ferrocenyl 'Scotch tape.' The resulting "novel trifunctional conjugates" purport to treat chloroquine-resistant P. falciparum strains with low-micromolar potency.

Chirality? At that carbon?

A few salient questions: First, if these compounds represent med-chem advances, why are they in Organometallics, of all places? Surely this wasn't the first Editor's desk they landed upon! Second, both papers seem to be variations on a theme, so why not just combine them and make one stronger paper? Lastly, can anyone interpret the stereochemistry shown in this intermediate? It's drawn to suggest a chiral acetal; my o-chem 'spider sense' says that cannot be. 


To my med-chem inclined readers: what do you make of these molecules? Bandwagon hype, or real advance?


Update, 6/15/12 - Changed figure caption, and "ketal" to "acetal"

Houston, We Have 'Level A' Protection

We just wrapped up our annual HAZWOPER training, and I've always bemoaned that it's all Powerpoint and quiz questions, without enough "hands-on" activities. Well, that certainly changed this year!

Although I'm a bit late for Lab PPE Day (this isn't really a lab setting anyway), this was my first time in a Level A suit. Wearing this feels exciting, but mildly disorienting: it's like walking through heavy snow, with both dexterity and visual impairment.

Dressing up this way gives me an even greater appreciation for everything the astronauts are able to accomplish in NASA space suits. Alas, although we tested spill kits, used gas meters, and drilled placards, freeze-dried ice cream was not served.

Stay safe, everyone!

Blast from the Past: 1998 C&EN "Golden Age" Roundtable

Sadly, these "scientists" were not
included in the '98 roundtable
Credit: Universal Pictures

It's always risky business, peering into the future. But that doesn't stop anyone, even chemists, from trying!

Regular readers recall that Chemjobber and I recently teamed up to bring you two perspectives on the inaugural Organometallics roundtable (2012). Of course, this wasn't the first time wily ACS Editors tried this tactic: check out Chemistry's Golden Age, a panel organized to commemorate the 75th anniversary of C&EN by (not-quite-yet-Editor-in-Chief) Rudy Baum in 1998.

Moderated by blog mainstay Ron Breslow, the distinguished group included heavy hitters from a wide sweep of the field: Allen Bard, Richard Zare, Stephen Lippard, Koji Nakanishi, Robert Langer, and Nobelist Richard Smalley (RIP). (I especially enjoyed seeing the "young whipper-snappers" on the panel: Dan Nocera, Barbera Imperiali, and Jacqueline Barton.)


Since we're only about a decade away from affirming their predictions, I figured we'd peek back to see what yesteryear's chem blogs - no doubt on AOL, Prodigy, or GeoCities - might have covered.

#Chemjobs - Optimism reigned, as you might expect from the biotech boom of the late '90s.
Bard: "I think as long as chemists keep getting jobs, there will be chemistry departments...as long as we can turn out students who can find employment, we'll be okay." Yikes. Anyone else?
Barton: "I predict there will be fewer chemistry departments, but not fewer chemists." Well, don't mention that to CJ or Derek. 
Langer: "Some universities have gotten rid of departments, sure. But chemistry? If they're going to get to the point where they're going to get rid of chemistry, that just seems to me like a very long way to go." Reminds me of a funeral procession I saw recently, for a country closing many of its departments...


Energy - Smalley: "Twenty-five years from now the internal combustion engine will be found in museums, battery technology will finally have solved the problem of how we transport electrical power, and fuel cells will be practical devices...We may have solved the problem of cheap solar energy" 
I'll agree with the fuel cell argument, but I don't think we've advanced batteries or solar far enough (yet) to mothball our gas-guzzling autos...though Lippard correctly presages the rise of electric cars. Fossil fuels were "hot" topics: Stuart Rice and Bard both favored (pre-Incovenient Truth) investigation of alternate energy sources to combat global warming.

Young Danial [sic]
Nocera waxes
...artificial life.?
Source: C&EN

Origin of Life - Dan Nocera, he of water-splitting 'pacman' and 'hangman' catalysts, didn't mention anything about them, but instead placed his chips behind artificial membranes and building functional cells; Zare and Breslow both jumped right on board! Maybe they all hung out with Venter back in the day?


Times-are-a-changin' - The terms "bionic man," "Pentium chip," and "electronic publication" all sneak into the discussion.


Computers - "Unfettered optimism." This panel had grown, published, and worked with computers. They envisioned stunning things ahead.

"We can rebuild him,
using a 56K modem and
an Apple IIe!"
Credit: jackm's blog

Breslow: "Within 25 years, most reaction mechanism studies of the kind that we do now on simple reactions will be replaced by computational studies..." Yup.
Theodore Brown: "The combination of combinatorial chemistry and computational methods may lead us to the point where we actually have a library of catalysts designed to do specific things." Uh-huh. 
Smalley: "One of my favorite dreams is developing true spectroscopies for individual molecules..." Check.

Publishing - Funny, for computer-literate panelists sponsored by a magazine, group members remained stodgily entrenched in printed paper.
Bard (then Editor of JACS), referred to online papers: "I don't think it is going to be popular among chemists." Imperiali, who must have been plagued by pop-up ads: "The volume of material on the Internet is getting out of control. And the quality control has to go down because of the volume." 


Smalley, ever the visionary, really sees what's coming: "In 25 years, we will be getting our journals transmitted directly to a little thing that will feel like a book...I can't imagine waiting for a piece of paper to arrive in Texas before I read it." He would have loved Nooks, Kindles, and iPads.


Bold Move - From Allen Bard, wise words:

"If I have to make a prediction about the future, I would predict that five of the most important things that will be developed in the next 25 years have not been discussed at this table."

Truly a statement for all seasons. I've searched the text, and I find no mention of quantum dots, organocatalysis, MOFs, C-H activation, or even the reactions knocking on the Nobel Committee's door: palladium cross-coupling and olefin metathesis. I'll certainly keep this bon mot in mind, so I can conclude future roundtables this way...


Final Thought - You could easily criticize this roundtable for being strongly academia-leaning. The OM collection, though more well-rounded with Dow and DuPont reps, still lacks enough industry involvement. What do the folks in startups, "new energy," or science writers think about the future of our field?

*Readers, do you have recommendations for a different kind of panel?

Dear Slate: America Needs More Artists

(I scribed this parody piece in reponse to Slate's Hive post 'America Needs More Scientists and Engineers.' See Derek's In the Pipeline response, here.)

If you stare at the work long enough, you realize
that the man in the top hat sitting by the tree loves science
Source: artic.edu

When I was a college Freshman - back when there were Day-Glo paints but no Instagram - I dropped by the studios of the Fine Arts professors. I asked them what the future job market might be like for illustrators. They said, if I wanted to go into the 'creative' fields, I needed to devote myself to a discipline, say, early Mayan pottery, or pinhead sculpture. Later, I could become a generalist (which I think meant starting an internet comic).

It was the best advice I never followed. Today, I'm a lab researcher, sculpting compounds, drawing structures, and loving life. I ducked drawing murals for distilling solvents, social science for real science - another political cartoonist lost to America. I wouldn't have been a great artist, but I might have been OK.

America needs Thomas Kinkades and Andy Warhols, but it really needs a lot more good artists, more expressive artists, more mediocre artists, and more starving artists.

In theory, "artsiness" has never been cooler. America sanctifies Steve Jobs (the iPod designer), and envies da Vinci (the Renaissance man-cum-robotic surgeon). There are hipster sculptors, hipster poets, and hipster, well...hipsters. There's 20x200, an entire industry devoted to finding unknown artists, and letting you buy a slice. And yet, American art is in crisis: in this economy, gigs and commissions are tough to come by. Much of our great art comes from overseas (Italy, Japan, Russia) because there aren't enough artists here at home. And many of our best visual and musical minds are snatched up by mainstream media, producing viral apps (Draw Something) or 'selling out' their musical talents (American Idol).

In this piece, Pollock foresees the 2007 recession
Source: The Well-Read Fish

President Obama says we are facing a "Calvin & Hobbes moment." In a time of struggling economic recovery, record deficit spending, and rising student loan debt, we need someone able to scream for all of us, even if we can't. Who better to capture the rapture on the face of a Fortune 500 executive, as he poses for a bronze bust commemorating his latest restructuring? Who will sketch the unemployed as they wait with them in line for assistance checks? Who will take inverted pictures of "pre-abandoned" homes in a down housing market?

How can we educate more and better painters, inkers, writers, sculptors, singers, dancers, poets, chalkers, illustrators, comedians, lyricists, or underground graffiti artists? How can we repeat the successes of 500 years ago? How can we persuade kids with artistic inclinations to stay in the arts?

All month, Just Like Cooking will be mulling over this question...while running reactions and thinking about science. Readers, if you've got a notion - a Kodachrome flash bulb above your head - submit your art education ideas in the comment section.

Hi Ho, Silver! (Benzoate)

Ever feel déjà vu? You know, that feeling of having been somewhere before, or crossing a black cat twice?

Carbon dioxide - Silver benzoate "puts a ring on it"
Source: Yamada, et.al. ACIEE, 2012

I've been stalked lately by a certain catalytic reagent: silver (I) benzoate. It's everywhere! Here, Charette's using it for C-H activation, with a little dash of Pd, to produce heterocyclic drug leads. Here, Toste's group turns up the selectivity on a gold hydroamination. Just this week, Yamada and coworkers showed lactone formation via carbon dioxide fixation (see above), using a bit of pressure, some base, and...you guessed it, silver benzoate.


Makes me wonder: Did I somehow miss the signs? How long has this reagent been flying under my radar?

In 1957, the Lone Ranger
ruled the Silver Screen
Source: lonerangerfanclub.com

Quite a while, it seems. Name reaction buffs - have you heard of the Prévost? First developed in the 1930s, it produces an anti vicinal diester, forming two new C-O bonds from opposite directions on neighboring carbons. Later investigations into the "wet Prévost" reaction favored cis diols; not too shabby when you consider that the related osmium or iodonium variants were still several decades away.


In its heyday, the Prévost helped synthesize steroids, alkaloids, and polymers, and found its way into the hands of a Who's Who of the O-Chem 'golden age': Woodward, Fieser, Carothers, Winstein, Streitweiser, Gilman, Djerassi, Fries, Benkeser, Sondheimer, van Tamelen, and Witkop. Perhaps you're more of a mechanisms person? Check out this sweet ¹⁸O labeling work, courtesy of a young University of Washington chemist named Ken Wiberg (1957).

What about silver benzoate makes it so darn useful for these oxidations? First, you have a d¹⁰ late metal species, which loves to coordinate to π-bonds (alkenes, alkynes, allenes). Second, the softer nature of the resonance-stabilized benzoate might switch on different catalytic pathways, say, changing from inner- to outer-sphere. Finally, to the benzoate itself: our buddy Ken showed that it adds twice, producing a transient 5-membered, cyclic species that ultimately permits the second benzoate addition.

Adventures in Lab Supply

Science Fair Supply?

Example 1 - Ever heard of Science Stuff? It's a online store, usually serving the K-8 science fair market with chemistry kits, study guides, and classroom materials. They also sell 20-L solvent cans, filled to the brim with your favorite organic solvents!


I noticed this label (see right) on my 20-L dichloromethane just yesterday. We order our bulk solvents through the usual channels - Fisher, Aldrich, Acros - but these suppliers apparently subcontract to all sorts of interesting vendors. 


Fun fact: the same website sells gift certificates, just in case you'd like to send a loved one some chemicals; Bromoform for birthdays, perhaps chromates for Christmas?


Example 2 - Presented for your approval, our recent shipping papers for an order of fire extinguishers. When I heard this phrase I thought about a ghost, driving without a seatbelt.

Arsenic Life Wrap-Up: The Good, the 'Not-So-Good'

"Arsenic Life," a hot-button issue for much of the past year, reemerged this week with two new papers, one propitious, and one, well...not so much.

GFAJ-1 bacteria
Source: nasa.gov

As covered by Curious Wavef(n), the first paper related Prof. Rosie Redfield's well-documented efforts coaxing the GFAJ-1 strain to flourish in arsenic-rich media, which, if successful, would imply arsenate linkages in the bacterial DNA. Redfield bursts the bubble nicely, utilizing multiple tools (LC-MS, cell growth assays, gels) to cast doubt on the earlier study, even mentioning that most of the detected arsenate could be washed away with distilled water.

Well, if timing is everything, then the second #arseniclife publication really missed the boat. Last week, a commentary appeared in the open-access online journal Biomolecules, bearing the epic title From Phosphorus to Arsenic: Changing the Classic Paradigm for the Structure of Biomolecules. Heavy stuff!

This summary takes the opposite tack, casting "Dr. Wolfe-Simon's discovery" as a fighting underdog - viewed skeptically today, but enshrined and glorified by future generations much like Copernicus or Darwin (both name-dropped inside). The prose shakes the reader with thrilling, emphatic statements, lines you might find in a rousing stump speech or an action movie. A few choice selections:

"...Some have died as a result
of these discussions..."
Image Credit: Silver Lining

"It is no surprise that this work has come under what some may consider a brutal attack in the past year; the proposed repercussions almost beg of it."

"...members outside of the scientific community may view the criticisms and other events that have transpired as superfluous, vindictive, and outright scathing." 

"...the implications of [arsenic life] have the potential to shake the foundation of biology as we have known it for centuries."

 "This discovery...would be absolutely groundbreaking to all of science."

You get the point. These excesses, coupled with a few cut-and-paste sources (N.B. Don't include "page-access" dates in references) and a passing remark to Wolfe-Simon's potential scientific martyrdom, complete the commentary. Yesterday, several Twitter denizens, led by the industrious Carmen Drahl, noted a very familiar vibe to this piece. To borrow a phrase from Derek and Leonid, it sounded suspiciously like a "term paper," final reports students submit to wrap up specific college courses.

My feelings, reading Paper #2
Source: Jobbing Scriptwriter

Was it? A very strong maybe. Check out this editorial, culled from the Colorado State University Journal of Undergraduate Research  (p. 16), scribed by the lead author. Bears a rather striking homology to the Biomolecules piece, sources* and all. The second author, currently an undergraduate at Boston University, may have interacted with the CSU authors at a conference, or perhaps on a summer REU.

As corresponding author, Prof. Mark Brown (CSU) would, I'd believe, have final say over the manuscript. Did he check it against the lead author's previous work? The journal's Author Information section mentions that five external reviewers must be named, although "...the Editor will not necessarily approach them."

So, to round up this bizarre publishing escapade, we have undergraduate authors submitting previous work in an open-access, loosely-reviewed, and barely-edited online journal, all with the benediction of a faculty member? Sounds dubious...much like arsenate linkages in DNA.

*Can someone please tell me where to find Ed "Young" at Discover Blogs? : )


Update, 6.8.12 - Commenter Stuart Cantrill (Editor, Nature Chemistry) points out on Twitter that the original piece also misspelled "phosphorous" in the title. Sigh.