Wednesday, November 19, 2014

"Unknown Unknowns" in Synthetic Biology

Update: Ash (@curiouswavefn) found a similarly structured article, this one in J. Med. Chem.

Somehow, I don't recall seeing this gem anywhere on the chemblogosphere...

Famed natural products chemist Jon Clardy wrote a 2014 perspective article in ACS Synthetic Biology. Interestingly he structured the content after former U.S. Secretary of Defense* Donald H. Rumsfeld's 2002 "There are known knowns" testimony. Remember it?
" we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns -- the ones we don't know we don't know."
Per the Clardy review, artemisinin (antimalarial) represents one of synthetic biology's well-researched "known knowns." Moving synthetic gene clusters for cryptic metabolites into more easily-cultivated host organisms meets the "known unknowns" criteria, whilst uncovering novel natural products with novel gene clusters and unidentified biological roles captures syn-bio's "unknown unknowns."

*And, lest we forget, former CEO of Searle Pharmaceuticals - poetically apt, here?

Wednesday, November 12, 2014

Chemistry Bumper Cars - Chris Walsh to Stanford?

Earlier tonight, while combing through the ASAPs, I came across an interesting situation:

Usually. the chemblogosphere catches major moves fairly fast, but have we missed this one? Perhaps this is a "courtesy appointment," though I can't find any mention on Stanford's site.

Anyone know anything?

Monday, November 10, 2014

Candid Chemistry - 2014 Edition

Occasionally, readers will send me funny pictures that somehow capture the chemistry cultural zeitgeist. Here's some from the last few months:

At MIT, you can apparently chain your bike to a caffeine molecule!

Seen at UC-Berkeley: the ultimate chemical Doom tribute
( this guy)

Still frame from LeVar Burton's charity read of Go the #*&@ to Sleep
Does anyone recognize the (fake) elemental symbol poster? Geordi would never approve.

Attn, Chemjobber: from Austria, a promotional poster extolling the virtues of chemical employment!
(and a hip song to go with it!)

Heartfelt thanks to everyone who sent one in. Keep 'em coming!

Invisibly Important

Who does more important work: The scene-stealing front man, or the patient show-runner backstage?

Sumac in Fall, 2014
Writing at the New York Times "Motherlode" blog, author David Zweig posits that, in an era of attention-grabbing occupations - Internet whiz-kids, Wall Street financiers, American Idols - the real winners may be those who select the quiet, thoughtful "enabler" roles behind the scenes. He claims that, though they may not get the glory, such "Invisibles" end up better paid and more highly satisfied with their chosen stations.

Though Zweig volunteers occupations like structural engineers or quantitative analysts, I'd offer that most important roles in scientific research belong equally on his list: Spectroscopists. Molecular modelers. Patent examiners. Grant writers. Purification staff. Procurement. Health and Safety. Administrative assistants. Graduate students.

If you get a chance today, think about the Invisibles that help your science to succeed.
And buy that mass-spec guy a beer, already!

Friday, November 7, 2014

Friday Fun - Maitotoxin Watch

For those keeping tabs on K.C. Nicolaou's potential career capstone, the group has published another fragment (QRSTUVWXYZA') of the ladder polyether maitotoxin. By my count (and thanks to their handy graphic, below), they've now formed 30 of the 32 requisite rings, meaning we'll likely see a completed total synthesis in the next few years.*

Top: Maitotoxin
Bottom: Previously disclosed fragments
Source: Nicolaou | JACS 2014 ASAP

When Nicolaou's group announced the move to Rice, one of my first thoughts was "who gets to personally chaperone the maitotoxin fragments to their new home?" I'm picturing combination-locked black suitcases handcuffed to postdocs' wrists, but perhaps the samples just went in the back of a U-Haul truck with all the other lab equipment.

Happy Friday,
See Arr Oh
*Assuming they can work out the ring fusion and selective sulfate chemistry - not trivial tasks by any means!

Tuesday, November 4, 2014

Strange Cover Art

A small part of me remembers a time before journal articles could all be accessed online. Back then, the cover art -- a creative expression of some of the newly-reported research between the covers -- could swing you towards one journal over another as you milled around the musty library stacks.
Source: Wiley-VCH, c. 2014 / ACIEdoi: 10.1002/anie.201409223

Nowadays, we've lost some of that artistic tradition, save for notable standouts Nature Chemistry and Angewandte Chemie. Hence, my confusion when looking at this week's Angewandte cover art - does anyone understand what's going on here? 

Best I can tell, this graphic is a nod to Prof. Younan Xia's excellent overview of the benefits and risks inherent to nano-scale research. But the graphic appears (to me, anyway) to resemble two angry Pokemon fighting over the sword from Legend of Zelda. About the only chemistry I see? Blink, and you'll miss it: along the blade are five tiny emblems meant to represent common nanostructures such as carbon nanotubes or micelles. 

Readers, am I missing something obvious here, or does this not really communicate the depth of Prof. Xia's review issue?

Monday, September 22, 2014

Honing Halophilicity

Let's say you have a late-stage drug candidate, with an alcohol, an olefin, and a pyridine. Now you toss in one equivalent of a chlorinating reagent.

Which functional group gets halogenated first?

Babak Borhan and colleagues from Michigan State and Dow may have your answer. In a recent JACS full article, they disclose the HalA (halenium affinity) scale, a DFT-calculated delta to describe the relative reactivity of various groups to an incoming halogen source. They back up their calculations with NMR competition studies, showing, for example, that two structurally similar molecules have a rather skewed 7:1 equilibrium, as predicted by a 1.1 kcal / mol difference in HalA:

Borhan et. al., JACS 2014
Using 500 computationally-evaluated functional chlorenium "acceptors" (Lewis bases), Borhan and colleagues create a chart to help answer our initial question: What reacts first?

I'm certain even more detailed versions of this chart are currently underway. I wonder how well it would extend to prediction of methyl or trifluoromethyl group additions?